Combating Diseases Associated with Poverty - CiteSeerX

Combating DiseasesAssociated with PovertyFinancing Strategiesfor Product Developmentand the Potential Role ofPublic-Private Partnerships

Principal Authors

Roy WiddusKatherine White

A report on the status of the field based on aworkshop of the same title organized by theInitiative on Public-Private Partnerships for Health

The aim of the Initiative on Public-Private Partnerships for Health is to increasethe effectiveness of public-private collaboration, particularly by helping thoseseeking to develop health products, or to improve access to such productsneeded to fight neglected diseases and other health problems in developingcountries.

Created in 2000 in Geneva, Switzerland, the Initiative on Public-PrivatePartnerships for Health is sponsored by the Bill & Melinda Gates Foundation,the Rockefeller Foundation and the World Bank. It operates under the aegisof the Global Forum for Health Research, an independent internationalfoundation helping to correct the 10/90 gap in health research, from which italso receives support (www.globalforumhealth.org).

www.ippph.org

Initiative on Public-Private Partnerships for HealthInternational Center Cointrin • Block G • 3rd Floor • 20, route de Pré-Bois

PO Box 1826 • 1215 Geneva • Switzerland

Tel: (+41 22) 799 4086/4073 • Fax: (+41 22) 799 4089E-mail: [email protected]


Principal Authors

Roy Widdus, Initiative on Public-Private Partnerships for Health, SwitzerlandKatherine White, Consultant, United Kingdom


In collaboration with:

Bill & Melinda Gates FoundationDepartment for International Development (United Kingdom)Rockefeller FoundationWellcome Trust

Held on 15–16 April 2004at the Wellcome Trust, London, United Kingdom

ABRIDGED VERSION

Combating Diseases Associated with PovertyFinancing Strategies for Product Development and the Potential Role of Public-Private Partnerships

Principal authors: Roy Widdus and Katherine WhiteEditor: Sue PfiffnerManaging Editor: Roy Widdus

© The Initiative on Public-Private Partnerships for Health, Global Forum for Health ResearchPublished by the Initiative on Public-Private Partnerships for Health, Global Forum for Health ResearchNovember 2004ISBN 2-940286-21-3

The reproduction of this document is regulated in accordance with the provisions of Protocol 2 of the Universal Copyright Conven-tion. All rights are reserved by the Initiative on Public-Private Partnerships for Health, Global Forum for Health Research. Thedocument may be freely reviewed and abstracted, with the usual acknowledgement of source, but not for sale or for use in conjunc-tion with commercial purposes. Requests for permission to reproduce or translate the report, in part or in full, should be addressedto the Initiative on Public-Private Partnerships for Health where information on any translations or reprints is centralized (seeaddress above).

The named authors alone are responsible for the views expressed in this publication.

Designed by minimum graphicsPrinted in Switzerland

The Initiative on Public-Private Partnerships for Health (IPPPH)ICC, Block G, Third Floor20 Route de Pré-BoisP. O. Box 18261215 Geneva 15Switzerland

E-mail: [email protected]: www.ippph.org

IPPPH SECRETARIATRoy Widdus, Ph.D.Ms Armelle Armstrong (until 30 June 2004)Ms Pamela AtiaseMs Amelia BonacuaMs Sandra Botta (until 30 June 2004)Ms Karin Holm

OtherMs Katherine White, ConsultantE-mail: [email protected]

Contents

Dedication v

Acknowledgements vi

Abbreviations and acronyms vii

Preface ix

Messages xi

Executive summary 1

Historical context: Why public-private partnerships for product developmentemerged and how? 3

Meeting summary 21

Areas for future attention 35

Moving forward 41

Post-workshop consultation on ‘Meeting Summary’ and ‘Areas for Future Attention’ 43

Annexes

Annex 1. Agenda 47

Annex 2. List of participants 49

Annex 3a. Background on the PD PPPs under consideration 55

Annex 3b. Background on the concept of the workshop 65

Annex 4. Purpose of the meeting: Opening Remarks 69

Annex 5. Millennium Development Goals 72

Annex 6. Keynote address 73

Annex 7. Questions by Sessions 75

Annex 8. Background papers’ key messages 79

Annex 9a. Estimates of the medium term financial resource needs for development ofpharmaceuticals to combat ‘neglected diseases’ 84

Annex 9b. The emerging landscape of public-private partnerships for product development 98

Annex 9c. PPPs and product development: Innovative financing opportunities and the needfor a ‘business case’ approach 139

Annex 9d. Portfolio management in the pharmaceutical industry 156

Annex 9e. Demonstrating value: Performance metrics for health product developmentpublic-private partnerships 159

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C O M B A T I N G D I S E A S E S A S S O C I A T E D W I T H P O V E R T Y

Annex 9f. The current research-to-development ‘hand-off’ process for productconcepts/candidate products and possible improvements in it 164

Annex 9g. Ethical review capacity: Country needs, role and responsibility of partnersand researchers 169

Annex 9h. Current status of clinical trials in Africa 173

Annex 9i. Emerging lessons in preparing for uptake of new vaccines 179

Annex 9j. The costs of developing vaccines: Case study of VaxGen’s HIV candidate vaccine 188

Annex 9k. Requirements for vaccine product and field site development at alicensure standard 192

Annex 9l. Product development public-private partnerships for diseases of poverty.Are there more efficient alternatives? Are there limitations? 196

Annex 10. Donor consultation on policy and programming for PD PPPs: Minutes 206

Annex 11. Consolidation of the Private Partnerships for Product Development: Africa’s Role 210


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Dedication

This volume is dedicated to John La Montagne who committed his life to improv-ing health, particularly for those disadvantaged by poverty. His memory will be

long cherished by all who had the privilege of knowing him as a professional col-league and personal friend.

Acknowledgements

IPPPH would like to thank the following organizations for their financial, in-kindand intellectual support which made the workshop on Combating Diseases Associ-

ated with Poverty: Financing Strategies for Product Development and the PotentialRole of Public-Private Partnerships and this book, in abridged and full versions,possible:

• Bill & Melinda Gates Foundation• Department for International Development (United Kingdom)• Global Forum for Health Research• Rockefeller Foundation• Wellcome Trust• World Bank


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Abbreviations and acronyms

ADIPs Accelerated Development andIntroduction Plans (GAVI)

AHRF African HIV Research ForumAMANET African Malaria Network TrustARVs antiretroviralsBVGH BIO Ventures for Global HealthCABs Community Advisory BoardsCANs development candidatesCDC Centers for Disease Control and

Prevention (United States)CIDA Canadian International Development

AgencyCMM Capital Markets Mechanisms

working group (World Bank)CONRAD/ Contraceptive Research andCICCR Development Program/Consortium

for Industrial Collaboration inContraceptive Research

DAH development assistance for healthDECs disease-endemic countriesDFID Department for International

Development (United Kingdom)DNDi Drugs for Neglected Diseases initiativeDSMB data safety and monitoring boardDSS demographic surveillance systemsDTP diphtheria-tetanus-pertussisEDCTP European and Developing Countries

Clinical Trials PartnershipEMEA European Medicines Evaluation

AgencyEMVI European Malaria Vaccine InitiativeEU European UnionFDA Food and Drug Administration

(United States)FIND Foundation for Innovative New

Diagnostics

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FTE full-time equivalentGATBDD Global Alliance for Tuberculosis

Drug Development (TB Alliance)GAVI Global Alliance for Vaccines and

ImmunizationGCP good clinical practiceGDP gross domestic productGFATM Global Fund to fight AIDS,

Tuberculosis and MalariaGFUNC Gates Foundation/University of

North Carolina Partnership for theDevelopment of New Drugs

GMP Global Microbicide ProjectGSK GlaxoSmithKlineHepB hepatitis BHHVI Human Hookworm Vaccine

InitiativeHib Haemophilus influenza type bHRP Human Reproductive Programme

(WHO)IAVI International AIDS Vaccine InitiativeIBRD International Bank for

Reconstruction and Development(World Bank)

ICH International Conference onHarmonization

IDA International DevelopmentAssociation (World Bank)

IDRI Infectious Disease Research InstituteIFC International Finance Corporation

(World Bank)IFF International Finance FacilityIFPMA International Federation of

Pharmaceutical ManufacturersAssociations

IOWH Institute for OneWorld Health

IP intellectual propertyIPM International Partnership for

MicrobicidesIPR intellectual property rightsIPPPH Initiative on Public-Private

Partnerships for HealthIRB Institutional Review BoardJICA Japanese International Cooperation

AgencyLAPDAP Lapdap Antimalarial Product

DevelopmentLMICs low and middle income countriesMCA Millennium Challenge Account

(USA)MDGs Millennium Development GoalsMDP Microbicides Development

ProgrammeMHRA British Medicines and Healthcare

Products Regulatory AgencyMMV Medicines for Malaria VentureMSF Médecins sans Frontières (Doctors

without Borders)MVI Malaria Vaccine InitiativeMVP Meningitis Vaccine Project at

WHO/PATHNEPAD New Partnership for Africa’s

DevelopmentNGO non-governmental organizationNIH National Institutes of Health

(United States)ODA official development assistanceOPIC Overseas Private Investment

CorporationPABIN Pan-African Bioethics InitiativePAHO Pan American Health OrganizationPATH Program for Appropriate Technology

in HealthPD product developmentPDVI Pediatric Dengue Vaccine InitiativePEI polio eradication initiative


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PH-ROI public health return on investmentPMA portfolio management approachPneumoADIP Pneumococcal Vaccines Accelerated

Development and Introduction PlanPPPs public-private partnershipsR–D–A research–development–accessR&D research and developmentRFPs requests for proposalsROI return on investmentRotaADIP Rotavirus Vaccines Accelerated

Development and Introduction PlanSAAVI South African AIDS Vaccine

InitiativeSOPs standard operating proceduresSTIs sexually transmitted infectionsSVI Albert B. Sabin Vaccine InstituteSWAps sector-wide approachesTAM traditional African medicinesTB tuberculosisTBDI Tuberculosis Diagnostics InitiativeTDR UNICEF/UNDP/World Bank/

WHO Special Programme forResearch and Training in TropicalDiseases

TPPs target product profilesUNAIDS Joint United Nations Programme on

HIV/AIDSUNDP United Nations Development

ProgrammeUNFPA United Nations Population FundUNICEF United Nations Children’s FundUSAID United States Agency for

International DevelopmentUSAIDMVDP USAID’s Malaria Vaccine

Development ProgramVF Vaccine FundWHO World Health OrganizationWRAIR Walter Reed Army Institute of

Research

Preface

While they draw upon skills and procedures that arewell established in the commercial sphere, these prod-uct development PPPs are essentially ‘social experi-ments’. ‘Best practices’, proven by the delivery ofproducts, are not yet available. The desire to know howto assess the added value of these ventures, as well as‘partnership proliferation’, are high on the agenda ofconcerns for both existing and prospective funders suchas bilateral aid agencies. These funders also need toknow the scale of future resources needed.

These same funders and many other entities, includ-ing the World Bank, UNDP, WHO and developingcountry governments, are currently seeking ways toachieve the UN Millennium Development Goals(MDGs), adopted in September 2000, and other in-ternationally agreed targets.1 Of these MDGs, halfrelate directly or indirectly to health, and one specifi-cally calls for a partnership with the pharmaceuticalindustry to provide access to affordable essential medi-cines.2

At present, however, it seems very unlikely that theMDG targets for 2015, and particularly the health-related ones, will be achieved in most of the poorercountries. Unfortunately, the debate on achieving theMDG targets has not recognized that the array of‘tools’ available to meet the international targets onchild mortality, HIV/AIDS, tuberculosis (TB) andmalaria are inadequate for the poorer countries. Major

Public-private partnerships for health productdevelopment: Why a critical review now?

In the mid-1990s, some fundamentally different ven-tures began to emerge addressing the development

of products for combating diseases associated with pov-erty. These have come to be known as public-privatepartnerships (PPPs) although some prefer other de-scriptive phrases. Collaboration on an ad hoc basis andaround individual candidate projects had, however,occurred previously between public sector agencies andprivate sector pharmaceutical companies.

What distinguishes these new ventures is that theytake as their starting point not a (‘favourite’) specificcandidate product, but a survey of the field and thenpromote the parallel development of a range of differ-ent candidate products (a ‘portfolio’). Managementof a portfolio, borrowed from the pharmaceutical andventure capital fields, is designed to manage the risk offailure accompanying any individual project. Prior tothe mid-1990s, no public-interest venture engaged inproduct development had articulated ‘portfolio man-agement’ as a conscious strategy. Some of the productdevelopment ventures considered at the 15–16 April2004 meeting convened by the Initiative on Public-Private Partnerships for Health (IPPPH) in Londonhave, as yet, only small portfolios. However, the olderventures have at least five to six years of operationalexperience and sizeable portfolios, some over 25 projects.

The emergence of these new ventures was initiallyfostered by the Rockefeller Foundation and subse-quently, around the turn of the millennium, by sub-stantial funding from the Bill & Melinda GatesFoundation. Their number is presently approaching20. More new ventures to address currently unmetneeds (for example, for control of noncommunicablediseases) may possibly emerge.

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1 The UN General Assembly Special Session on HIV/AIDSDeclaration of Commitment: Three million people – 2 millionin Africa – receiving treatment by the end of 2005.The Abuja targets for malaria in Africa: By 2005, ensure 60%of those with malaria have access to appropriate treatment.The Amsterdam target for tuberculosis: By 2005, 70% ofpeople with infectious TB will be diagnosed and 85% cured.

2 Goal 8, Target 17, Indicator 46.

causes of child mortality, such as pneumococcal pneu-monia and rotavirus diarrhoea, lack preventive vaccines.There is no vaccine or microbicide to prevent HIVinfection, no vaccine for malaria and no vaccine to pre-vent the majority of TB cases (in adults). Existingdiagnostic tools or therapies for most diseases associ-ated with poverty are old and/or difficult to use. Mostdrugs are threatened by increasing resistance.

Given this situation, the Initiative on Public-PrivatePartnerships for Health concluded that taking stock of


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experience to date would help a range of constituen-cies to maximize the value of their future investmentsof money and effort in product development. Partner-ships, we hope, can learn from each other; existingdonors can compare and contrast practice for adjust-ing their support; and prospective funders can see whattypes of ventures most closely align with their missions.Finally, a new dimension can be added to the debatesabout achieving the MDGs, namely improving thearray of tools that can facilitate their achievement.

Roy Widdus, Ph.D.Project Manager

Initiative on Public-Private Partnerships for HealthGlobal Forum for Health Research

Geneva, Switzerland

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Public-private partnerships to combathealth problems associated with poverty

Message from the World Health Organization

Message from the International Federation of Pharmaceutical Manufacturers Associations

the Foundation for Innovative New Diagnosis, as wellas broader coordination mechanisms, like the GlobalAlliance for Vaccine and Immunization and the StopTB Partnership.

Such collaborations strengthen the overall globalmovement for better health. WHO welcomes these andthe other new ventures addressing neglected diseases.They support our shared goal, and WHO’s underly-ing mission, to ultimately break the deadly cycle of dis-eases and poverty in which – even in today’s globalizingworld – too many individuals are still trapped.

LEE Jong-wookDirector-General

World Health Organization

For decades, the research-based pharmaceutical in-dustry has fostered the development of new medi-

cines and vaccines that have saved lives and improvedthe health of millions of people around the world. Notonly have these innovations helped the poor by deal-ing with major causes of the global burden of disease,but the pharmaceutical industry has also developedproducts needed to combat conditions that affect pri-marily the health of poor populations.

Some commentators have expressed misgivings thatas global competition among companies increased,there would be less attention to the needs of the poor,particularly as the costs of bringing new innovative

products to the market increased. Fortunately, allmajor R&D-based companies continue to address theneeds of poorer populations through a variety ofmechanisms. These include research collaborations;donation programmes or differential pricing policiesfor poorer populations; special packaging and formu-lations; initiatives to assure quality and discourage coun-terfeit medicines; and educational, training and otherprogrammes to strengthen the infrastructure andhuman resource capacity for the delivery of healthcareservices.

The accumulated expertise and experience repre-sented in research-based pharmaceutical companies is

The mission of the World Health Organization(WHO) includes fostering research and product de-

velopment to address the health problems that burdenits Member States, particularly the poorer ones.

Significant contributions to this goal have been madeby various WHO implemented programmes, such asthe World Bank/UNDP/WHO Special Programmefor Research and Training in Tropical Diseases (TDR),the UNDP/UNFPA/WHO/World Bank Special Pro-gramme of Research, Development and Research inTraining in Human Reproduction (HRP), and morerecently the Initiative on Vaccine Research. We antici-pate a continuing role for these programmes.

Over the last few years, WHO has also participatedin the development and launch of some new not-for-profit ventures that complement WHO core role. Theseinclude, the Medicines for Malaria Venture, the Glo-bal Alliance for Tuberculosis Drug Development, and


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a major resource for global health. It would be waste-ful to duplicate this or not to recruit it to social pur-poses, such as those represented by the MillenniumDevelopment Goals. Linking private sector expertisewith public sector goals to combat global health prob-lems obviously makes sense.

R&D-based companies welcome the emergingarray of new ventures – so-called public-private part-nerships – specifically addressing diseases associatedwith poverty. These ventures facilitate the processesby which industry can utilize its unique strengths –expertise for innovative product development – to ad-dress the needs of the poor. These new ventures alsorepresent disciplined ways of working toward successin a timely manner, approaches familiar to industry andnecessary for the efficient and effective use of every-one’s resources.

IFPMA, the official representative of the pharma-ceutical industry’s innovator companies worldwide,

welcomes the opportunities that these new venturescreate to address the critical needs of those who stillsuffer disproportionately from the health problemsassociated with poverty. Investing in health is the sur-est way to find the path to economic development andgreater wealth. Public-private partnerships have animportant role to play in achieving that worthy andambitious goal.

Raymond V. GilmartinChairman, President and

Chief Executive Officer, Merck & Co., Inc.President, International Federation of Pharmaceutical

Manufacturers Associations, 2002–2004

Executive summary

E X E C U T I V E S U M M A R Y

Background

In the mid-1990s, a new group of not-for-profit ven-tures addressing the development of health products

for combating diseases associated with poverty beganto emerge. This phenomenon resulted from trends inthe late 20th century including awareness of diseaseburden distribution, changing pharmaceutical indus-try economics, and the emergence of ‘champions’ fortackling specific health inequities. To mitigate risks aris-ing from individual project failures, these venturesadopt the pharmaceutical industry approach of devel-oping various candidate products simultaneously andrecruit, to varying degrees, industry collaboration intheir efforts. Hence, they have become known as‘public-private partnerships’ (PPPs), although someprefer other descriptive phrases. About 20 PPPs nowexist, some relatively new with small portfolios; othershaving over six years’ experience and managing size-able portfolios of more than 25 products.

While they have underlying similarities, these ven-tures also vary, particularly owing to factors arising fromtheir choice of disease target (HIV/AIDS, malaria,tuberculosis or other) and product focus (drugs,vaccines, diagnostics, microbicides or other healthproduct).

Workshop summaryOn 15–16 April 2004, a workshop entitled Combat-ing Diseases Associated with Poverty: Financing Strate-gies for Product Development and the Potential Role ofPublic-Private Partnerships was organized by theInitiative on Public-Private Partnerships for Health(IPPPH), part of the Global Forum for Health Re-search, in collaboration with the Bill & Melinda GatesFoundation, the UK Department for InternationalDevelopment, the Rockefeller Foundation and the

Wellcome Trust which hosted the workshop at theirLondon headquarters.

The workshop was organized around five objectives:

• Provide background on the emergence and op-erations of these ventures.

• Consider how product development (PD) PPPsand other players operate and interact.

• Assess the current and future financial needs ofPD PPPs.

• Assess if innovative financing options for diseasesof the poor exist.

• Identify questions and issues requiring furtherattention and study.

During the workshop and an associated consultationamong existing PD PPP funders, it became clear thatPD PPPs could be considered a coherent grouping orfield albeit with differences around individual venturesarising mostly from their choice of disease and prod-uct focus which significantly affects the context in whichthey operate.

The main themes in the discussions were:

• Agreement, generally, that the PD PPP model(albeit with variations) was a sound and cost-effective approach to product development fordiseases associated with poverty, probably the bestthat could be currently identified.

• Interfaces with other organizations in theresearch–development–access (R–D–A) con-tinuum were critical and a major managementchallenge for PD PPPs. This encompassed bothupstream interfaces with basic research, down-stream interfaces with potential delivery systems,effective management of interfaces with privatesector collaborators and ‘contractees’ in the spe-cific steps of product development, and links with

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researchers and policy-makers in disease-endemiccountries (DECs).

• Effective portfolio management is a critical fac-tor allowing PD PPPs (and donors) to spread risksof individual project failure, thus favouring ulti-mate success. In addition, the technical expertiseof PD PPP staff and Scientific Advisory Boardsprovided added-value to funders who may nothave, or wish to have, the in-house scientificcapacity to manage product development them-selves.

• Consideration was needed of the activities re-quired to achieve optimal access for the poorerpopulations in need of the anticipated healthproducts. Identifying necessary actions becomesmore important where delivery systems are noteasy to identify or function poorly. The PD PPPsmay be in a good position to advocate for thenecessary actions but responsibility for implemen-tation probably more appropriately rests withother players.

• The financing required for product developmentwill vary given the disease/product choices of thePD PPP. Based on estimates of funds committedby early 2003, and cost estimates for the port-folio of products underway, the financing short-fall through 2007 for major PD PPPs appears tobe at least US$ 1.2 billion and possibly overUS$ 2.2 billion, depending on assumptions.Techniques for assessing the amounts necessaryneed to be refined. Nonetheless, PD PPP pro-jections and estimates from independent sourcesprepared for the workshop using industry costsas reference suggest a large shortfall in the nearterm. This shortfall exists, even for the best-

funded PD PPPs, as well as across the field. Cred-ible certainty about financing can affect the levelof collaboration from industry.

• Judging ‘success’ is important to funders andrequires the development of comparative per-formance measures.

• Communication and coordination among allplayers is critical to the field, as cooperation of somany players (funders, PPPs, industry, DECs,etc.) is required to ensure progress of candidateproducts along the R–D–A continuum. Currentlevels are probably suboptimal, but mechanismsneed to be ‘light’ as most players are alreadystressed by current obligations.

Areas for future attentionParticipants did not prioritize conclusions and recom-mendations at the workshop. However, subsequentconsultation among the meeting chairs and sessionco-chairs, funders and PD PPPs identified some con-sensus on areas for future attention:

• Development of common performance measures.• Coordination of clinical trial capacity develop-

ment.• Harnessing the potential of disease-endemic

countries.• Ensuring financial sustainability of the PD PPPs.• Communication and coordination.• Fully recruiting potential industry contributions.

These are discussed further in the report from theworkshop, along with possible approaches to movingforward. First, however, some historical context is pro-vided, for readers new to this field.


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E X E C U T I V E S U M M A R Y

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Historical contextWhy public-private partnerships for product

development emerged and how?Roy Widdus

necessary for effective control (preventive, diagnostic,and therapeutic) and in their appropriateness for usein resource-constrained developing country settings.5

Table 1 shows recent WHO estimates of the mor-tality and disease burden arising from selected condi-tions that disproportionately affect poor populations.In many cases specific disease burden estimates havebeen developed for the major contributors to diseaseburden within broad categories of health problems.For example, rotavirus within diarrhoeal diseases orpneumococcal pneumonia within lower respiratoryinfections, respectively cause an estimated 500,000 to800,000 and 800,000 to 1 million deaths annually.6,7

While Africa represents around 11% of the global popu-lation, it accounts for around 55% of the deaths frominfectious and parasitic diseases. Tropical diseases,which particularly afflict the poor, represent a signifi-

The reason that a wave of new multi-candidates/portfolio-based ventures for product development

to combat ‘diseases predominantly associated with pov-erty’1 arose in the late 1990s has not been subject toextensive examination. Analysis of the emergence ofindividual ventures does not help with our general un-derstanding of this phenomenon, as such analysis of-ten tends to focus on the disease burden that aparticular venture hopes to alleviate and the scientificprospects for new products. As analysis shifts to changesin the environment in which the ventures emerged, itbecomes somewhat more speculative but worthattempting. Trends in the late 20th century that prob-ably created an environment conducive to the burgeon-ing of these new ventures are discussed below. Such ananalysis, however, cannot define the relative contribu-tion of different factors in their emergence.

Trends in the late 20th century conducive toemergence of PD PPPsThe last two decades of the 20th century saw a numberof trends that created a fertile environment for theemergence of new ventures against diseases associatedwith poverty. These are briefly described below.

Systematic analysis of the global burden of diseasehighlighted diseases associated with poverty anddeficiencies in tools to combat themWork on the rich-poor health inequalities2 and globalburden of disease3 led to wider recognition that forthe world’s poorest, infectious diseases still currentlyrepresent the major differential cause of prematuredeath and disability.

Analysis further identified the deficiencies in thetools available to tackle many of these diseases.4 Suchdeficiencies exist both in terms of the array of tools

1 Sometimes termed ‘neglected diseases’, although some, suchas HIV/AIDS, receive considerable funding overall.

2 World Bank. 1993. World Development Report: Investing inHealth. World Bank. 320 pp.

3 Murray CL, Lopez AD. 1996. The Global Burden of Disease.World Health Organization and Harvard University Press. 990pp.

4 Ad Hoc Committee on Health Research. 1996. Investing inHealth Research. World Health Organization. 278 pp.

5 Preventive vaccines are lacking (HIV/AIDS, malaria) or poorlyeffective in adults (TB) for the major killers. Easy to use, af-fordable drugs are lacking (HIV/AIDS) or are threatened byresistance (malaria, TB), and diagnostic tools are outdated (TB)or lacking (malaria). For the diseases predominantly limited totropical settings (trypanosomiasis, leishmaniasis), similar prob-lems can be outlined along with few currently available thera-pies, which are mostly unsatisfactory due to toxicity or difficultyof use. For global pathogens that mainly kill those in develop-ing countries, e.g. rotavirus and pneumococcus, vaccines areonly just now becoming available and introduction needs tobe accelerated.

6 See: www.rotavirusvaccine.org.7 See: www.preventpneumo.org.


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cant debilitating burden of disability (as measured indisability-adjusted life years [DALYs]) even though inoverall terms they cause relatively few deaths.

Pharmaceutical companies faced increasing R&D costs,consolidation and greater competitive pressures, increasingtheir aversion to commercially risky or unattractive projectsIt is generally accepted that in the latter decades of the20th century, the R&D-based pharmaceutical indus-try faced rising costs for bringing each new product tothe market (even if the exact costs are debated).

One response to this situation was mergers and ac-quisitions creating a relatively small number of ‘mega-companies’, competing intensively for shareholderinvestment and each seeking ‘blockbuster’ projectscapable of generating annual revenues in the multi-

Table 1. Estimates of deaths and burden of disease by various causes for 2002

Deaths (%) DALYs (%)

(000) (000)

Total 57,029 100 1,490,126 100

Communicable diseases, maternal and perinatal conditionsand nutritional deficiencies 18,324 32.0 610,319 41.0

Infectious and parasitic diseases 10,904 19.1 350,333 23.5

Tuberculosis 1,566 2.7 34,736 2.3HIV/AIDS 2,777 4.9 84,458 5.7

Diarrhoeal diseases 1,798 3.2 61,966 4.2

Childhood diseases (vaccine preventable) 1,124 2.0 41,480 2.8

Malaria 1,272 2.2 46,486 3.1

Tropical diseases 129 0.2 12,245 0.8Trypanosomiasis 48 0.1 1,525 0.1Chagas disease 14 0.0 667 0.0Schistosomiasis 15 0.0 1,702 0.1Leishmaniasis 51 0.1 2,090 0.1Lymphatic filariasis 0 0.0 5,777 0.4Onchocerciasis 0 0.0 484 0.0

Dengue 19 0.0 616 0.0

Japanese encephalitis 14 0.0 709 0.0

Lower respiratory infections 3,884 6.8 91,374 6.1

Nutritional deficiencies 485 0.9 34,417 2.3

Noncommunicable diseases 33,537 58.8 697,815 46.8

Injuries 5,168 9.1 181,991 12.2

Source: World Health Report 2004. World Health Organization, Geneva, Switzerland.

million, preferably billion dollar range. Some sourcessuggest that as of 1997, most major pharmaceuticalcompanies would have no interest in products with an-ticipated annual revenues of less than US$ 300,000,1

a level higher than expected for many of the productsneeded to tackle diseases of poverty.

All these trends rendered it increasingly unlikely thatcompanies alone would invest their own R&D re-sources in products to combat diseases predominantlyaffecting poor populations.2

1 Mercer Management Consulting. 1997. Report prepared forthe Children’s Vaccine Initiative.

2 Activist calls for greater ‘corporate social responsibility’ didnot emerge until around 2000, and – in reality – probably playless of a role in overall decision-making (by companies andinvestors) than profitability.

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H I S T O R I C A L C O N T E X T

Vaccines are increasingly ‘orphan’ products, despite theirpublic health importance in developing countriesPreventive vaccines continued to comprise a smallerfraction of the total pharmaceutical market, and mostmajor companies focused on a selected rather than acomprehensive range of candidates in development –overwhelmingly for affluent markets.

Vaccines, as compared to drugs, are relatively unat-tractive commercial products. This results from anumber of factors:

• Vaccine development requires major but risky in-vestment in product-specific manufacturing plant(for clinical trials) before the certainty of a market-able product (and revenues) is established. (Drugmanufacturing on the other hand can be scaled upafter efficacy is established.)

• Purchasers of vaccines (generally governments) aremore price-sensitive and able to negotiate lowerprices (hence lower margins) than patients seeking(drug-based) therapies.

• The target population for vaccines – healthy indi-viduals – requires close to absolute safety and side-effects discovered post-marketing (e.g., Wyeth’srotavirus vaccine) can cause expensive product with-drawal.

For vaccines against the major three poverty-relateddiseases (HIV/AIDS, TB and malaria), the scientificpathways to a successful product are uncertain, but willbe relatively expensive, since likely efficacy must beestablished in large human trials.

Understandably, this situation leads to lower inter-est by major companies in vaccine development in gen-eral and to even lower interest in vaccines withpredominant demand in poorer populations.

The HIV/AIDS pandemic draws global attention to the needfor greater action on health needs of low- and middle-income countriesThe increasing impact of the HIV/AIDS pandemic onpoor populations, especially in sub-Saharan Africa, wasknown to international public health specialists fromthe mid-1980s onwards. However, most ‘activism’ inthe 1980s and early 1990s was confined to affluentcountries and directed principally to the needs ofaffected individuals in such settings.

In the early to mid-1990s, the availability of

multidrug, antiretroviral (ARV) therapy led to the pos-sibility of extending the lives of people with HIV/AIDSby a significant degree, albeit at high cost.

With the wide availability of ARVs in industrializedcountries, the difference in prospects for poor, as com-pared to rich, patients led to a new wave and directionfor HIV/AIDS activism. Starting in the mid-1990s,calls to make treatments for HIV/AIDS more widelyavailable, and at much lower price, in developing coun-tries increased substantially, and from many differenttypes of organizations.

Those undertaking advocacy and ‘activism’ for bet-ter access of those in developing countries to HIV/AIDS treatments also promoted, to varying degrees,greater awareness of the need to improve access to treat-ments (or prevention) for other diseases, such asmalaria, tuberculosis and trypanosomiasis.

This spillover effect raised general awareness of dis-eases associated with poverty and the need to ensurebetter tools for their control. The general climate ofopinion shifted towards higher expectations that R&D-based pharmaceutical companies would do somethingabout developing country health needs.

Public health and public interest organizations improvetheir understanding of industry motivations and productdevelopment expertiseAn additional factor that may have played a role in theemergence of the new PPP ventures is better recogni-tion in public health and public interest organizationsof the value of approaches used in industry and betterunderstanding of its underlying economics andmotivations. While no systematic study has been con-ducted, a number of anecdotal examples can be foundthat suggest that this may have played some role innew venture creation.

From the late 1980s to the mid-1990s, the UNDP/World Bank/WHO Special Programme for Researchand Training in Tropical Diseases (TDR) increasinglyincorporated explicitly the aim of product development.In this period, staff with industry experience werebrought into the programme in significant numbersand positions for the first time. These included the ar-chitects of the Medicines for Malaria Venture (MMV,see below).

From the early 1990, WHO and UNICEF, underthe stimulation of the Children’s Vaccine Initiative


6

(CVI), undertook studies on the economics of com-mercial vaccine supply for developing countries andon vaccine production. These studies and the generalincreased interaction with industry under the CVIprobably led to better recognition of industryapproaches and motivations. Certainly, the architectsof the process that led to IAVI (described below) werefamiliar with these lessons.

This better understanding of industries’ approachto product development on the part of public healthor public interest (philanthropic) organizations, in andof itself, was not probably sufficient to trigger theemergence of PD PPPs.

It is likely that those with industry experience inpublic sector organizations (such as WHO) and thosein private philanthropic foundations wishing to‘borrow’ from industry to achieve success recognizedthat what was necessary could not be accomplishedwithout a flexible new ‘hybrid’ approach.

The emergence of discrete ventures dedicated toproduct development for neglected diseasesAdoption of the multi-candidate/portfolio approachby ventures committed to global public health (as ameans of enhancing likely success) appears to haveoccurred in various independent circumstances particu-larly in the mid- to late 1990s. Each represents recog-nition of the necessity for effective public-privatecollaboration, from different starting points.

Antecedents of the not-for-profit product developmentventures in infectious diseasesAntecedents of the portfolio-based, not-for-profitinfectious disease PD PPPs emerging in the mid-1990scan be seen in some research programmes on contra-ception. The principal example is the ContraceptiveResearch and Development Program (CONRAD),which was established by the US Agency for Interna-tional Development in 1986 at the Eastern VirginiaMedical School to expedite new contraceptive devel-opment. CONRAD conducts and funds activities acrossmultiple R&D projects for contraceptives and, nowa-days, microbicides.

At the same time as IAVI and MMV were emerg-ing, CONRAD and its supporters developed a Con-sortium for Industrial Collaboration in ContraceptiveResearch (CICCR), formally established in 1995. Based

on the belief that risk sharing in the early stages of theproduct development process could attract industry’sinvestment in much needed contraceptive and micro-bicide research, CICCR was set up to:

• identify leads under investigation in not-for-profitinstitutions, in both developed and developing coun-tries, that could result in new contraceptivemethods in the priority areas specified by thewomen-centred agenda of the 1994 Cairo confer-ence; and

• encourage industry to collaborate with CICCR byproviding support to investigators at not-for-profitinstitutions.

Even though there is no commercially marketed prod-uct as yet, the industrial partnerships established haveenabled CONRAD to take a product into late-stageclinical trials. The partnerships have also resulted indeveloping a knowledge base at CONRAD applicableto other candidate products in the pipeline. These ven-tures thus adopted elements of the approach that wasalso embraced independently by the ventures describedbelow.

The emergence of the first PD PPP for vaccine development:International AIDS Vaccine InitiativeVarious discussions occurred in the late 1980s and early1990s regarding the need for expanded efforts onvaccines to combat HIV/AIDS. These took place inboth formal meetings convened by the US Institute ofMedicine and the World Health Organization, and in-formally among an interested group in association withinternational meetings on AIDS, such as that in Berlinin 1993, with an increasing focus on the needs of lessdeveloped countries. Individuals involved in these dis-cussions included José Esparza, who continued tomanage WHO – and subsequently UNAIDS – activi-ties on HIV/AIDS vaccines; Don Francis, who foundedVaxGen Inc., to test an early candidate, AIDSVAX; andSeth Berkley, who took forward the approach outlinedbelow.

On 7–11 March 1994, the Rockefeller Foundationconvened at its Bellagio Conference Facility a meetingentitled Accelerating the development of preventive HIVvaccines for the world. The Rockefeller Foundation hasa long history in philanthropy for global public healthand the meeting’s principal architect was Seth Berkley,

7


a public health epidemiologist with experience of theearly HIV/AIDS epidemic in Uganda, then workingat the Foundation.

The meeting’s 24 participants concluded, inter alia,that:

“…the development and testing of multiple empiri-cal approaches in a parallel fashion rather thansequentially, will be a faster route to the develop-ment of safe, effective and inexpensive vaccines ap-propriate for widespread [i.e., developing country]use, …but one which industry alone was unlikely totake because of lack of commercial incentives forthe developing country market.”

They additionally concluded that:

“Success in developing an HIV vaccine will requirethe involvement of both public and private sectors”.

but stressed that, given the commercially unattractivedeveloping country market:

“Positive steps will have to be taken if pharmaceuti-cal and biotechnology companies are to be encour-aged to commit more fully their expertise, experienceand resources to the development of a preventiveHIV vaccine.”

While the meeting was exploratory, it concluded thata new initiative was needed and laid out a set of char-acteristics and activities, which would be necessary forthe mission to be pursued effectively.1

Further meetings were sponsored by the RockefellerFoundation, under the guidance of Seth Berkley, on ascientific agenda2 (also co-sponsored by the Founda-tion Mérieux) and on financial and structural issues3

which laid the groundwork for the International AIDSVaccine Initiative (IAVI).

IAVI became an independent legal entity in 1996.Significantly the Bellagio participants concluded:

“Experience with drugs and vaccines for other dis-eases suggests that measures will need to be takento ensure that once a vaccine is developed it isaccessible to those at risk of infection throughoutthe world with the least possible delay.”

This statement presaged a major component of IAVI’sactivities. Subsequent to initiation of its productdevelopment activities (see 4,5), it launched efforts inaddressing ‘access’.6

IAVI thus originated in the recognition by the pri-vate philanthropic sector of a global public health need.Its adoption of a ‘portfolio’ approach was driven mostlyby the realization – independent of industry – that thismaximized the chances of getting to a useful productwith the least delays. For the most part, securing in-dustry engagement, in projects or to the overall ven-ture, was left to the new entity, post-creation. Industryexpertise was recognized as necessary, but so was theneed to go beyond industry’s usual role, into advo-cacy and access for poor populations to anticipatedproducts.

Medicines for Malaria Venture: The first PD PPPfor drug developmentShortly after the Rockefeller Foundation initiated theprocess that led to IAVI, staff within the UNDP/WorldBank/WHO began discussions that ultimately led tothe creation of the Medicines for Malaria Venture(MMV). These discussions were initiated by two indi-viduals, Win Gutteridge and Robert Ridley, who knewproduct development and the benefits of a portfolioapproach in increasing the probability of success fromtheir prior experience in the pharmaceuticalindustry.7 When working with Wellcome and Glaxo-Wellcome, Gutteridge had written position papers high-lighting the need for special new efforts to ensurecontinued attention to the need for drug developmentfor ‘tropical diseases including malaria’.

The major issues that arose during discussions aboutrevitalizing anti-malarial drug development to meet

1 Rockefeller Foundation. 1994. Summary report and recommen-dations of an international meeting: HIV vaccines – Accelerat-ing the development of preventive HIV vaccines for the world.7–11 March 1994, Bellagio, Italy. 27 pp.

2 Rockefeller Foundation. 1995. Summary report and recommen-dation of an international ad hoc scientific committee. 27–28October 1994, Le Val de Grâce, Paris, France. 24 pp.

3 Rockefeller Foundation. 1995. Summary report and recommen-dations of an international meeting: Financial and structuralissues. 17 August 1995, New York. 16 pp.

4 International AIDS Vaccine Initiative. Scientific Blueprint –1998. 22pp

5 International AIDS Vaccine Initiative. Scientific Blueprint –2000. 29pp

6 International AIDS Vaccine Initiative. 2000. AIDS Vaccinesfor the World: Preparing now to assure access. 55 pp

7 Ridley RG, Gutteridge WE, Currat LE. 1999. Unpublishedmanuscript presented at the 3rd Forum of the Global Forumfor Health Research, Geneva. New medicines for malaria: A casestudy of the establishment of a public/private sector partnership.


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developing country needs were those relating to in-dustry engagement and the nature of the venture thatwould be able most effectively to catalyse new productdevelopment. Industry endorsement and engagementwas actively sought and eventually negotiated throughinteractions with major companies facilitated by theInternational Federation of Pharmaceutical Manufac-turer’s Associations. An independent, not-for-profitlegal status was eventually accepted as the most appro-priate structural arrangement. The Rockefeller Foun-dation funded the first ‘business plan’ for a PD PPP,1

which reportedly helped increase credibility of the newventure with prospective funders.2 Various othergroups, including the Global Forum for Health Re-search, facilitated the creation and early operations ofthe nascent venture. MMV was established under Swisslaw as a foundation in 1999.

Thus, the first PD PPP for drug development waschampioned by individuals convinced of the need toapply industry methods (in portfolio management) topublic health goals, and who saw full industry engage-ment as essential from the outset.

These examples illustrate a theme recurring in re-view of PD PPPs, namely, underlying similarities inobjectives but differences in the process through whichthey are attained.

Role of Foundations in nurturing and expanding thefield of product development partnershipsTwo foundations have been instrumental in the start-up and funding of various PD PPPs. These are theRockefeller Foundation through their Health EquityProgram and the Bill & Melinda Gates Foundation(B&MGF), whose greatly expanded endowment in1998/99 allowed it to become a major investor in com-bating diseases associated with poverty.

Rockefeller’s involvement started with the forma-tion of IAVI. When IAVI was founded, Seth Berkley,then at Rockefeller, left to lead the organization. Fol-lowing Berkley’s departure, the new leadership in thehealth area at the Rockefeller Foundation (LincolnChen, Tim Evans and Ariel Pablos-Mendez) contin-ued its tradition of interest in application of scientificresearch for control of neglected diseases. Fostering

its application to specific diseases became a compo-nent of the Foundation’s programme in health equity.

In addition to IAVI, where it played a pivotal role,and MMV, where it contributed to a new dimension(the business plan), the Rockefeller Foundation hasfostered the creation of a number of other PD PPPs inthe last few years.

Typically, this has been through funding and organ-izing a broad consensus development process, whichsometimes lasts up to two years. This process has suc-cessively included specific studies that are coming tobe recognized as essential for a comprehensive ap-proach: a scientific situation assessment and plan; apharmaco-economic assessment (of need, market, costsand economics); and an assessment of access issues.

Ventures launched following ‘incubation’ by theRockefeller Foundation (other than IAVI and MMV)include:

• Global Alliance for Tuberculosis Drug Development(TB Alliance) (2000), which also benefited at itslaunch from endorsement and significant ‘seed’funding from the B&MGF

• International Partnership for Microbicides (IPM)(early 2001)

• Pediatric Dengue Vaccine Initiative (PDVI) (2001)

In late 1999, the Rockefeller Foundation suggestedthat the Global Forum for Health Research create aninitiative to monitor the various emerging PPPs andidentify what appeared to be predictors of success. Thissuggestion led to the creation of the Initiative on Pub-lic-Private Partnerships for Health (IPPPH) under theForum’s legal auspices in 2000.

Since the inception of its global health programme,the Bill & Melinda Gates Foundation has consistentlydevoted a major portion of its grant-making to port-folio-based public-private partnerships for productdevelopment.

The B&MGF provided a significant infusion of re-sources to already established PD PPPs (IAVI, MMV,Sequella Global TB Vaccine Foundation [see also dis-cussion of Sequella/Aeras below] and the Tuberculo-sis Diagnostics Initiative [TBDI]) at the time of theendowment expansion. Other PD PPPs were in an in-dependent process of formation at this time or laterand also benefited (for example, the TB Alliance,IOWH, IPM and PDVI).

1 Prepared by the Boston Consulting Group. 2000.2 Chris Hentschel. 2004. Medicines for Malaria Venture. Per-

sonal communication.

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In other cases, ventures were relaunched (FIND, asit evolved from TBDI) or launched exclusively (HHVI)or overwhelmingly (MVI) with B&MGF funding.

Unlike those ventures ‘incubated’ by the RockefellerFoundation, most ventures that owe their origins pre-dominantly to the Bill & Melinda Gates Foundationtend not to have undertaken a wide consultation andconsensus development process prior to the start ofoperations. Their support base, at least in financialterms, remains very narrow.

The B&MGF has significantly funded certainsingle candidate product development ventures, includ-ing the Meningitis Vaccine Project at PATH.

It should be noted that in addition to PD PPPs, theBill & Melinda Gates Foundation has also funded otherventures and activities addressing major healthproblems of the poor, including micronutrient malnu-trition (Global Alliance for Improved Nutrition),reproductive health, and infectious diseases control.

Emergence of other PD PPPsA number of the PD PPPs addressed in this book andthe prior meeting originated through processes differ-ent to those described above. For example, the Insti-tute for OneWorld Health was launched independentlyfrom the foundations noted above. Some evolved intotheir current model from earlier, significantly differ-ent, incarnations.

The current Foundation for Innovative New Diag-nostics (FIND), which was established as a Swiss foun-dation in 2003, is in the early stages of assembling aportfolio of candidate diagnostic products. However,its antecedents date back to 1996, first as a very smalldevelopment programme for tuberculosis diagnosticswithin the World Bank/UNDP/WHO TDR and laterwith the same mission and hosted status but with mas-sively increased funding (in 1998) from the Bill &Melinda Gates Foundation. Its current status andbroader mission resulted from discussions in 2002/03regarding the best status to enable the fullest possiblerange of flexible, timely operations and interactions withcommercial organizations.

Originally, the Sequella Global Tuberculosis Vac-cine Foundation was created in loose association witha small biotech company. Its early orientation was to-wards strengthening capacity to enable other organi-zations to develop and test products. In 1999, the

B&MGF provided US$ 25 million for these activities.In 2003, the organization adopted a new name (Aeras)and reoriented its strategy to encompass productdevelopment per se and in 2004 received a furtherUS$ 82.9 million for its activities.

The processes for creating PD PPPs evolveas do the ventures themselvesChampions appear to play a significant role in the emer-gence of PD PPPs but as the field develops, other ele-ments seem to be emerging as reasonable predictorsof a successful launch with broad-based support. Theseinclude:

• an inclusive process for achieving consensus on themission of a new venture and the activities mostneeded;

• a scientific review/blueprint;• a pharmaco-economic study, to define the need and

possible market;• a business case/business plan, which describes the

problem that the venture will address, the activitiesneeded to accomplish the goal, how they will beundertaken, and the resources required to do them;and in some cases,

• an ‘access’ plan, particularly in those cases wherethe path to use is otherwise unclear, since no deliv-ery system is immediately apparent.

Some champions, or organizations, forgo these stepsand move straight to creating a new venture and hop-ing to garner broader support in due course. Thesetend to start their operations with a narrow base offunders (sometimes only one). To date, most venturesstarted in this manner have remained with a narrowfinancial base.

Product development partnerships examinedat the IPPPH London meeting1

A widely accepted and consistently used definition of‘public-private partnerships for health’ remains elusive.The term is sometimes used (perhaps inappropriately)

1 This listing, and the IPPPH London meeting of 15–16 April2004, focused on ventures addressing infectious diseases. TheContraceptive Research and Development Program and itsConsortium for Industrial Collaboration in ContraceptiveResearch (CONRAD/CICCR) use a portfolio approach to newcontraceptive development. See Partnerships Database:www.ippph.org



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to cover private sector delivery of health services, therules for which are actually solely government control-led.

One proposed working definition includes “com-bining different skills, expertise and other resources –ideally in a framework of defined responsibilities, roles,accountability, and transparency – to achieve a com-mon goal that is unattainable by independent action”.1

This definition still includes a variety of mechanismsand participants, and covers many public-private col-laborations targeting product development in differ-ent ways.

As alluded to in the Preface, public-private collabo-ration for development of products to combat ‘ne-glected diseases’ did not arise de novo in the mid- tolate 1990s. The defining feature of the new ventureswhich started to emerge at that time is that they electto foster the simultaneous development of a numberof candidate products portfolios, rather than startingwith any specific (‘favourite’) project. This categorywas considered to include the following ventures:

HIV/AIDSInternational AIDS Vaccine Initiative (IAVI)South African AIDS Vaccine Initiative (SAAVI)Global Microbicide Project (GMP)International Partnership for Microbicides (IPM)Microbicide Development Project (MDP)

MalariaMedicines for Malaria Venture (MMV)Malaria Vaccine Initiative (MVI)European Malaria Vaccine Initiative (EMVI)

TuberculosisGlobal Alliance for Tuberculosis Drug Development

(TB Alliance)Aeras Global Tuberculosis Vaccine Foundation (Aeras)Foundation for Innovative New Diagnostics (FIND)

Other ‘neglected infectious diseases’Drugs for Neglected Diseases initiative (DNDi)Institute for OneWorld Health (IOWH)Pediatric Dengue Vaccine Initiative (PDVI)Human Hookworm Vaccine Initiative (HHVI)Rotavirus Vaccine Accelerated Development and In-

troduction Plan (RotaADIP)

Pneumococcal Vaccine Accelerated Development andIntroduction Plan (PneumoADIP)

This listing may be incomplete due to ventures using aportfolio approach on which IPPPH does not as yethave adequate information. At the time of the Lon-don meeting, BIO Ventures for Global Health (BVGH)was emerging; it is now described in Annex 3a, but isnot included in the analyses conducted for the meet-ing such as that by Sander and Widdus (Annex 9b).

Information on the various types of public-privatepartnerships for health is provided in a backgroundpaper prepared for the meeting, which also includesspecific information on these organizations.2

A current snapshot of the PD PPPs addressedSimilarities among PD PPPsThose closely associated with individual ventures (andcharged with selling their uniqueness to funders) willtend to emphasize differences among the crop of newproduct development ventures. However, impartialobservation can identify significant common, underly-ing characteristics across this group of new ventures:

• They use some private sector approaches (or re-sources) to attack R&D challenges

• They target one or more ‘neglected diseases’• They use, or intend to use, variants of the multi-

candidate/portfolio management approach• Their primary objective is public health rather than

a commercial goal• They are focused on developing products suited for

use in developing countries.

The other similarities among existing product devel-opment ventures stem from the nature of the productdevelopment process. While this is somewhat differ-ent for drugs and vaccines (and quite different for di-agnostics), there are again major similarities. Theprogression involved in turning scientific knowledgeinto widely applied disease control interventions isshown in Figure 1 and can be termed the Research-Development-Access continuum.

1 Widdus R. 2003. Public-private partnerships require thought-ful evaluation. Bulletin of the World Health Organization,81(4):235.

2 See annex 3a (Widdus R. Background on PD PPPs under con-sideration at the workshop).

1 1

Figure 1. Research-Development-Access continuum

This common continuum means that, to accomplishtheir mission, all product development PPPs need:

• the engagement of industry, public/governmentalagencies and civil society organizations as necessary;

• sufficient resources to implement their chosen strat-egies;

• strategies for management of intellectual propertyand leveraging R&D investments to assure productaccess for the poorest populations;

• access to clinical trial capacity;• access to regulatory experience including that

relevant to low- and middle-income countries(LMICs);

• access to expertise in assessing need, demand andmarkets for their products particularly in LMICs;

Investigationof productconcepts

Basicresearch

Candidatediscovery,

designs andpreclnical

Marketing(regulatory)

approval

Routineuse

Validationof wideutility

Manufacturing

Financing

POLICY

CLINICAL TRIALSIN DISEASE ENDEMIC COUNTRIES (DEC)

PRODUCTION PROCESS DEVELOPMENT

I II III

RESEARCH DEVELOPMENT ACCESS

Figure 2. Complementary capacities

Research capacity inDECs

Clinical trial capacity inDECs

Health system capacity inDECs

ADVOCACY

• access to expertise in assessing production optionsand their costs;

• knowledge of the best strategies for delivering prod-ucts to the poorest, including ways to work effec-tively with/within the existing health servicesinfrastructure;

• ways of measuring progress, in product developmentor delivery, or health status; and

• strategies for ensuring that non-contractual allies,in their collective efforts to develop and improveaccess to health products, actually fulfil their respon-sibilities and obligations.

For success in development and application of prod-ucts to combat neglected diseases, a range of comple-mentary capacities must also be engaged (Figure 2).



1 2

These may need strengthening in parallel but not nec-essarily by the PD PPPs themselves.

For comparing ventures, others may find it usefulfor PD PPPs to adopt similar approaches. Theseinclude:

• Expressing their goals in a way that facilitates meas-uring progress and productivity

• Expressing their potential public health impact in aconsistent fashion

• Projecting their financial needs, for funds both pass-ing via the venture and through other channels, toaccomplish their mission.

Underlying similarities between ventures may be ob-scured by the organizations’ desire to portray them-selves in particular ways or to emphasize slightlydifferent philosophies. For example, some describethemselves as ‘public-private partnerships’, whereasothers prefer to call themselves ‘not-for-profit phar-maceutical companies’ or ‘virtual pharmaceuticalcompanies’, and yet others ‘not-for-profit (R&D) ini-tiatives’. Some seem comfortable being portrayed ascollaborating closely with commercial pharmaceuticalcompanies and actively seek such representation in theirmanagement processes (e.g. MMV), whereas others,such as DNDi, put more emphasis on the public sec-tors’ responsibilities for ensuring product developmentfor ‘neglected diseases’.

Of necessity, all organizations tackling ‘neglecteddiseases’ collaborate with researchers and public healthauthorities in countries where these diseases areendemic. However, most do not regard capacitystrengthening, separate from product testing, as a pri-mary responsibility.

Variations among PD PPPs and their originsOne background paper prepared for the London meet-ing documents the variation among the PD PPPs un-der consideration along four themes:1

• Strategic variations• Financial variations• Sector roles and contributions• Operational variations.

One way to understand this variation, and even per-haps predict it, is to examine the consequences of themission chosen by those responsible for establishingthe new venture. Specifically, the choice of disease andproduct focus determine to a significant extent a widerange of factors around which PPP operations vary.

The product/disease focus determines the natureof the scientific challenge (in terms of likely difficulty)as well as the scientific environment in which the ven-ture starts to operate. Scientific research in some areasmay have been more badly neglected over time than inothers. This will make it more likely, and justifiable,that advocacy for the ‘field’ in general will be seen as anecessary task of a PD PPP, to ensure, for example, ithas sufficient leads from basic research. This choicealso affects the availability and range of commercial orother partners:

• A neglected field will generally have fewer potentialcollaborators either academic or commercial

• A partnership aiming to develop the first product inits class, or a new class of products (like micro-bicides), will have fewer potential commercialcollaborators

• Those developing vaccines (compared to drugs) willfind fewer collaborators interested in their activitiesand a very small number of major companies withvaccine development and large-scale manufacturingexperience.

These situations contrast with that of groups wherethe field has been reasonably active and a variety ofcollaborators exist to repeat well established scientifictasks, as is the case for malaria drugs.

Partnerships with fewer potential overall collabora-tors are more likely to be active along the wholeResearch-Development-Access continuum (includingadvocacy) and to undertake more activities ‘in-house’.These ventures are thus likely to need greater resources,principally because of the environment their missionbestows upon them.

The product/disease focus chosen also has signifi-cant implications for the potential uptake of products.For some combinations, more defined and/or betterfunctioning purchase and delivery systems exist. Forexample, purchase and delivery of children’s vaccinesand drugs for tuberculosis is usually by (or for) gov-ernments. But this is not true for vaccines for adults

1 See annex 9b (Sander A, Widdus R. The emerging landscape ofpublic-private partnerships for product development).

1 3

and adolescents, such as will, at least initially, be thecase for HIV/AIDS vaccines. Hence, IAVI identifiedthe need to address access issues for its target prod-ucts, as does IPM, which does not currently have anidentifiable delivery system for its products.

Partnerships developing products for which purchaseor delivery systems are less easily identifiable or func-tion less efficiently face the quandary of how to ensureuptake of their products.

Thus variations around ‘advocacy’ may reflect theperceived shortage of collaborators, while those around‘access’ activities may suggest the absence, or deficien-cies, in downstream uptake systems.

Other variations, e.g., doing more work ‘in-house’,may reflect choices governed to some extent by theperceived absence of suitable partners.

AdvocacyIn addition to activities strictly connected with prod-uct development, some PD PPPs elect to undertakevarious general communication and advocacy activi-ties. The extent and nature of these, to a large extent,are governed by their perceptions of the status of the‘field’ in which they operate and the position that theywish to occupy in it:

• All the ventures discussed here undertake commu-nication and advocacy activities directed at mobiliz-ing resources for their own mission.

• Some organizations (but not all) undertake to pro-duce and disseminate information on issues andprogress in their field of operations, aiming to bothincrease awareness and raise their own visibility. Ex-amples include the IAVI Vaccine Bulletin.

• Some organizations undertake analysis and advo-cacy on issues that they feel are related to the likeli-hood that they will accomplish their mission.Examples include the work of IAVI and IPM, pro-posing that a range of regulatory issues be clarifiedand that regulatory processes be harmonized be-tween countries.

• Advocacy on a slightly broader front is undertakenby some PD PPPs (such as the TB Alliance) for moreinvestment in their overall field, especially if it hasbeen neglected over a significant period of time.Similar motivations drive the advocacy activities ofDNDi for those neglected diseases that are confinedto the poorest population usually in tropical regions.

The choice of product/disease focus also has implica-tions in some cases for the existence of potential ‘ad-vocacy allies’ for pursuing the ventures’ mission(beyond collaborators strictly for product developmentactivities). Those engaged in HIV/AIDS can enlistgrass-roots activist organizations in many industrial-ized countries, but which do not exist for diseases likemalaria. Microbicide development groups can alignwith groups in both industrialized and developingcountries which seek to empower women (to bettercontrol their health risks). Where health professionalsassociate nationally or internationally around particu-lar diseases, these can also be useful allies for relatedPD PPPs.

AccessIf no delivery system is identifiable, a PD PPP may seea need to outline an ‘access’ plan. While an access planmight be useful in all cases (to document assumptionabout policy or financing), it is most clearly needed incases where no delivery system is immediately appar-ent. Where identifiable delivery systems exist but func-tion poorly, it is also arguable that an access plan couldfacilitate actions, in parallel to actual product develop-ment, to strengthen delivery, so that more of the po-tential impact of a new product was eventually achieved.Suggesting that PD PPPs prepare a plan identifyingsteps necessary to achieve access does not imply thatthey would necessarily be the implementers. Others,such as government or international agencies, mightbe more appropriate and indeed have formal responsi-bility for the necessary actions.

Understanding typical PD PPP operationsWhile variations among PD PPPs make it difficult togeneralize, some attempt is necessary so that readersnew to the field have a general understanding of theway most of the PD PPPs considered here operate.

Candidate products need to be moved at the fastestpossible speed and at reasonable cost through the vari-ous steps of product development. These have beendescribed in most detail for drugs,1 and are somewhatsimilar for vaccines, particularly at the clinical testingstages.


1 Nwaka S, Ridley R. 2004. Virtual drug discovery and devel-opment for neglected diseases through public-private partner-ships. Nature Reviews Drug Discovery, 2: 919—28.


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Figure 1 (above) represents this chain generally forboth drugs and vaccines. A more detailed picture fordrugs has been published by Nwaka and Ridley.1

It is possible for a candidate product to enter thesphere of a PD PPP’s influence at any point in theResearch-Development-Access continuum, but oftenthe venture negotiates the rights to develop further acandidate from an academic institution or companywhich typically hold patents on these.

To move any candidate product through the vari-ous product development stages requires certain typesof testing and subsequent decisions on whether it hassufficient promise to try to move through the nextstages. Failures, rather than successes, are the normand it is most cost-efficient if decisions to abandonprojects are made quickly and with the lowest expen-ditures.

To maximize the chances of success, it is best tohave a number of candidate products at each differentstage and to replace routinely those that are abandonedbecause the results of testing indicate problems, e.g.low efficacy, toxicity. This process of portfolio man-agement has been refined for drugs (see Schmid2) butless studied for vaccines.

Each testing step in product development requiresparticular expertise and resources, such as laboratoryequipment for synthesizing chemical variants of a

Figure 3. Balance of incentives and costs: MMV andpharma partner

JointR&D

MMV Invests$$$Background IPRLink to RBMExpertise

Public

Private

Pharma InvestsChemistry IPRToxicologyKnow-howAssets in-kindTechnologyLiability coverage

MMV GetsRights in DECIPR in ’field’Drug supplyReturn on non DEC sale

Pharma GetsRights in DECIPR outside ’field’PR benefitHR benefit

The ‘deal’ is sustaimed by balancing incentives/costs for each partner.

The win/win proposition:

candidate drug, animal models for toxicology testingor access to human populations at risk of the targetdisease or patients for testing candidate efficacy in pre-venting or treating it.

This expertise typically exists outside a PD PPP inother organizations individually (e.g., pharma compa-nies) or can be brought together in project teams. PDPPPs draw upon these companies or assemble collabo-rative teams through contracts for the activities con-nected with moving candidates through specifiedtesting steps. Based on the results of these activities,PD PPPs decide to pursue the candidate further orabandon it. Contracts are usually with organizationsthat share or support the PD PPPs’ public health goalsso the deals seek and often receive in-kind support (seeKettler and White 20033). Deals frequently seek tocombine contributions from different players thatultimately benefit both. This is illustrated in Figure 3.

Sufficient expertise and staff need to reside in thePD PPP to manage the organizations or project teamscontracted by it. If fewer potential collaborators canbe found to take on the necessary work, a PD PPP willneed to have a proportionally larger staff to manage orconduct activities ‘in-house’. The length, complexityand expense of product development means that wherethere is a paucity of candidates and few collaborators,the funding needed by the PD PPP and the likely timeto success will be greater.

The necessary expertise and composition of teamsassembled to move candidate products through differ-ent stages in the research and development process varywith product type and development step.

Figure 4 gives an idea of the complexity of somearrangements.

As the vast majority of collaborators engaged inmoving candidate products through testing steps areat a distance – physically and organizationally – fromthe PD PPP, the term ‘virtual R&D’ has been coinedto describe these arrangements, to contrast it with theprocess as historically practised in large pharmaceuti-cal companies, where most employees and activities

1 Ibid.2 See annex 9d (Schmid E. Portfolio management in the phar-

maceutical industry).3 Kettler H, White K. 2003. Valuing Industry Contributions to

Public-Private Partnerships for Health Product Development.Initiative on Public-Private Partnerships for Health, GlobalForum for Health Research, Geneva, Switzerland.

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were ‘in-house’.1 In recent years, small ‘biotech’ com-panies have pioneered virtual operations as a way ofconducting R&D with lower in-house investment instaff and equipment, thus maintaining their flexibility.Even large pharmaceutical companies are moving inthis direction.

Some commentators have noted the extra manage-ment demands that virtual R&D places on its spon-sors. However, there seems to be general agreementthat it is a cost-effective alternative to the duplicationby the PD PPPs or public sector organizations of ex-isting (expensive) physical infrastructure for possiblyshort-term projects.

Most PD PPPs are not currently funding activitiesintended to translate ideas from basic research intocandidate products (see Nwaka and Widdus2). Trans-lational activities are hence reliant on major biomedi-cal research funders, if they are undertaken at all.

The foregoing needs to be recognized as a generaldescription of PD PPP operations. Selected illustra-tions of product development partnerships in opera-tion, prepared by the named organizations, are includedbelow. Readers interested in more detail are referredto the Sander and Widdus background paper,3 plus theweb sites and annual progress reports of the individualorganizations.

Product development partnership in operation:Illustrations of the handling of typical challengesFrom the operations of the existing PD PPPs, espe-cially the older ones, a range of examples below havebeen selected to illustrate how they have met chal-lenges frequently encountered in the development ofhealth products.

Medicines for Malaria Venture (MMV)Creation and management of a not-for-profit portfolio ofcandidate malaria drugs■ MMV was challenged with the need to create andthen actively manage a ‘virtual R&D portfolio’ fromits founding in November 1999. At that point it hadidentified three drug discovery projects which met itsproduct-specification criteria. It had also accepted, in


Figure 4. The complexity of virtual R&D management: An illustrative project of the Medicines for Malaria Venture

Academia

MMV

Company

ConsultantsRBM

AdvisoryBoards

WHOExperts

ProjectManager

The Partnership

ProjectManager

ProjectManager Project

Manager

ProjectManager

LeadInvestigator

InvestigationalSite (1)

ClinicalContract ResearchOrganization (1)

InvestigationalSites

InvestigationalSites

ClinicalContract ResearchOrganization (2)

Non-clinicalContract Research

Organizations

Data Management/Biostatistics

ContractManufacturingOrganizations

Virtual R&D is essentially project andportfolio management throughrelationships and contracts

Investigator

Investigator

1 Recently, pharma and biotech companies themselves have beenadopting ‘virtual R&D’, for example, through contract researchorganizations.

2 See annex 9f (Nwaka S, Widdus R. The current research-to-development ‘hand-off’ process for product concept/candidateproducts and possible improvements in it).

3 Annex 9b (Sander A, Widdus R. The emerging landscape ofpublic-private partnerships for product development).


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its draft business plan (endorsed by its Board in March2000), the idea that to succeed it needed to manageits portfolio in line with the pharma industry’s ‘bestpractice’. Today it manages a balanced portfolio ofmore than 20 projects ranging from discovery to phaseIII trials. It became clear soon after its foundation thatthere were important differences between PPPs andfor-profit companies that would tend to alter such op-erational ‘best practice’. Where these differences exist,they need to be clearly understood and factored in byPPPs.

Since it was using public and philanthropic resourcesto create its ‘portfolio’, MMV adopted an approachthat was open and transparent to all interested parties.Roughly every two years, it issues a general call forproject proposals. About 100 proposals are received,of which generally 10 to 20 are considered the mostpromising based on a range of predetermined criteria.These proposals are then further evaluated by MMV’sstaff and its Expert Scientific Advisory Committee(ESAC). The ESAC is composed of a range of interna-tionally recognized malaria and drug development ex-perts, including individuals from industry. For all,conflict of interest procedures are followed. Depend-ing on the need to balance the portfolio, final selec-tions are made for funding. Historically, between 5–10%of the initial number of proposals are added to the port-folio.

In for-profit companies, it is clear that that R&Dinvestment is in the context of a general accountabilityto investors to maximize financial returns. In contrastPPPs have no way to ‘value’ their portfolios. The con-cept of a net-present-value related to future ‘DALY’saverted’ does not exist in public health. Accountabil-ity is to a broad group of stakeholders and is generallyexpressed in terms of a future ‘public health impact’ –but present metrics for such future impact are vague.R&D goals are usually expressed with surrogates (e.g.,MMV: one drug registered every five years) with a fo-cus on sustainability rather than on high-value exits.In this respect the idea that PPPs are like venture capi-tal funds (social venture capital was the concept thatjustified the V in MMV) is somewhat misleading.

Despite these differences the rationale for a port-folio management for MMV has easily been justifiedby three clear benefits. It has reduced risk by diversifi-cation of the project investments amongst several

chemical classes and therapeutic targets. It has fosteredinternal synergies between projects that should allowthe creation of added-value combinations of drugs thatare both more effective and less likely to generate re-sistance. It has significantly reduced costs by sharingenabling technologies between projects, by the flex-ibility it gives to shift resources from less to better per-forming projects and, crucially, by the greater ease itgives management to terminate projects that are notmeeting their milestones. Nothing saves more resourcesin pharmaceutical R&D that the ability to stop failingprojects early. MMV has already stopped four projects.

Global Alliance for Tuberculosis Drug Development(TB Alliance)A case study of PA-824 licensing■ The Global Alliance for TB Drug Development (TBAlliance) designs its contractual arrangements to enrolthe best scientific partners worldwide and to ensurethat the resulting technologies are affordable, accessi-ble and adopted by health-care workers and patientsin countries with the greatest need. The TB Allianceuses ownership or rights to intellectual property (in-cluding assignment, inventorship, licensing,sublicensing and other appropriate legal mechanisms)to balance its interests with incentives that make theindustrial development, production and commerciali-zation of new drugs economically feasible.

In 2002, the TB Alliance signed a landmark agree-ment with Chiron Corporation to in-license PA-824and its analogues. Recognizing PA-824’s potential asa tuberculosis (TB) therapeutic, Chiron was keen tolicense its intellectual property to an organization com-mitted to advancing its development for TB. The TBAlliance received worldwide exclusive rights to PA-824and its analogues for the treatment of TB and Chironpledged to make this technology royalty-free in en-demic countries. Chiron retained the right to developand commercialize the compounds for non-TB indi-cations.

The TB Alliance immediately devised and is under-taking a cost-effective development plan for PA-824,which is overseen by a development team with sup-port from the US National Institute of Allergy andInfectious Diseases. In its first two years of develop-ment, PA-824 has successfully passed major pre-clini-cal milestones and, if progress continues, could enter

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clinical trials in 2005. The TB Alliance is also pursuinga backup programme initially evaluating two analoguesof PA-824 that have demonstrated even greater po-tency in vitro than PA-824.

The PA-824 agreement demonstrates how the pub-lic-private partnership model can be leveraged to de-velop new products for the diseases of poverty and thatthe economic realities of drug development can co-exist with a social mission.

International Partnership on Microbicides (IPM)Royalty-free compound licence fromTibotec/Johnson & Johnson■ Since women are biologically and socially more vul-nerable to HIV infection than are men, preventiveoptions that women can use are critically importantcomponents of global efforts to stem the HIV/AIDSepidemic. The mission of International Partnership forMicrobicides (IPM) is to accelerate the developmentand delivery of microbicides, products that can be usedtopically to prevent HIV transmission, for women inresource-poor settings.

The ideal microbicide will kill or inactivate HIVbefore it can reach its target cell. A product that blocksHIV from attaching to or entering its target cell couldbe a second line of defence. Should the virus escape, athird approach is to inhibit HIV from replicating withincells, thus preventing it from spreading throughout thebody.

Currently, there are several classes of HIV thera-peutics that are being successfully used to treat HIV-infected patients, and pharmaceutical companies areactively pursuing development of new generations ofthese compounds. Many of these drugs could be for-mulated for topical delivery to prevent HIV infection.To address this need, IPM entered into an agreementwith Tibotec Pharmaceuticals Ltd, a subsidiary ofJohnson & Johnson, to develop the promising com-pound TMC120 as a microbicide. TMC120 belongsto the class of drugs known as NNRTIs (non-nucle-oside reverse transcriptase inhibitors), which are alreadywidely used therapeutically to treat people living withHIV/AIDS. This agreement marked the first collabo-ration in the microbicide field between a major health-care company and a public-private partnership such asIPM.

Tibotec developed TMC120 as an oral AIDS drug

in the early 1990s, but has since adapted it into a gelthat is currently in phase I clinical trials. Under thearrangement, Tibotec provides a royalty-free licenceto IPM to develop, manufacture and distributeTMC120 as a microbicide in resource-poor countries.Additionally, IPM will look to develop other formula-tions with TMC120, both alone and in combinationwith other active ingredients. Under the agreement,Tibotec will bear the cost of the compound throughphase II testing and will remain active as a scientificadvisor.

Agreements such as this benefit both organizations.Through these arrangements, IPM and other non-profit microbicide developers can significantly expandthe pipeline of promising candidates for development.Pharmaceutical companies can minimize the risks(proof-of-concept; regulatory; market size) of devel-oping a new class of products by transferring the de-velopment of the drug to another entity. Should theproduct be licensed, both IPM and Tibotec will haveachieved their goals.

International AIDS Vaccine Initiative (IAVI)Underpinning AIDS vaccine developmentthrough laboratory networking■ The current tests used to measure the immuno-genicity of HIV vaccines are relatively new and can behighly variable in terms of protocols and reproducibil-ity. Standardization across multiple clinical trial sitesand products is, therefore, a challenge not only to IAVIbut the field. The IAVI Core Laboratory was estab-lished so that valid head-to-head comparison of multi-ple candidate HIV vaccines could be made.

The IAVI Core Laboratory, based at Imperial Col-lege, London, UK, performs immunogenicity evalua-tions of IAVI-sponsored AIDS vaccine candidates.Volunteers who participate in trials have blood takento assess whether a vaccine induces a measurable im-mune response. IAVI currently sponsors clinical trialsof four different HIV vaccines, which are under way at15 trial sites in Uganda, Kenya, South Africa, the UK,Belgium, Germany, Switzerland and the US, in addi-tion to sites in Rwanda and India which are poised tocommence their first HIV vaccine trials. In each of thesetrials, volunteers’ blood must be processed so thatimmunogenicity assays can be performed. An absoluterequirement of operating vaccine trials at multiple sites



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is that a valid comparison be made between perform-ance of different vaccines both within and across trials.Furthermore, this data must be collected under con-ditions in accordance with internationally recognizedstandards. These issues are especially important in thesearch for an AIDS vaccine, in light of the overwhelm-ing public health consequences of achieving shortenedvaccine development timelines – a major goal of IAVI.

In order to facilitate valid comparisons, the IAVICore Laboratory receives samples from all clinical trialsites to test. The tests at the core laboratory have beenvalidated according to international standards and thelaboratory environment is also accredited. In additionthe laboratory is the focal point in the effort to stand-ardize procedures across all sites engaged in separat-ing blood and testing samples from trial volunteers.Activities that are key to standardization include pro-viding validated Standard Operating Procedures(SOPs), standard reagents, standard validated equip-ment, on-site and field site training and support of trialsite staff, in addition to acting as a primary field labo-ratory for IAVI-sponsored trials under way in London.Furthermore, IAVI holds workshops in which trial labo-ratory staff are invited to learn and henceforth applythe principles in line with regulatory authority guid-ance for data submission in support of vaccines.

The net outcome of using one laboratory to coor-dinate the entire IAVI programme, through provisionof identical operating procedures, reagents and train-ing, ensures the data are reproducible across sites inidentifying positive responses. Thus IAVI benefits fromthis through being an accredited lab, hence assuringthe quality of the data. Trial sites benefit from this set-up through reducing the lead-time required for involve-ment, and also the one-stop direct assistance providedby the core lab. Both the sites and core lab team ben-efit from being brought together in the wider trainingefforts, which aid staff and hence site development,and also from the sense of partnership, unity and com-bined purpose in the greater effort of developing anAIDS vaccine.

The vaccine network field benefits through the trans-parent and collaborative work that the core lab partici-pates in. This occurs with other groups in the HIVvaccine network and outside, such as the TB Initia-tive, both through exchange of SOPs, and within theHIV vaccine network participation in proficiency tests.

These collaborations help move us closer to being ableto compare data across networks, which will benefitthe field in driving towards the goal of an HIV vac-cine.

Aeras Global Tuberculosis Vaccine FoundationPreparing for large-scale clinical efficacy trials■ Recognizing that testing of new vaccines for effi-cacy against tuberculosis would represent a significantlogistical challenge and potential bottleneck, the pred-ecessor to the Aeras Global TB Vaccine Foundation(then named the Sequella Global Tuberculosis Foun-dation) initiated a programme to anticipate this need.

South Africa was chosen for the development of aclinical site and of human resource capacities, becauseof the prevalence of TB and the level of existing capac-ity there. At the time of early discussions, the SouthAfrican Government had made the decision to switchfrom percutaneous administration of a locally manu-factured strain of the Bacillus Callmette-Géurinvaccine (BCG Tokyo) to the intradermal administra-tion of Danish-manufactured BCG strain 1331. Thisoffered the opportunity for development of clinicaltrials capacity in the Boland-Overberg region of West-ern Cape Province (east of Cape Town) through theconduct of a randomized, controlled trial of an exist-ing TB vaccine, at the same time answering immediatescientific questions.

Enrolment began in March 2001 and was completedin July 2004 with the enrolment of 11,677 neonateswithin 24 hours of birth. In addition, blood was col-lected at 10–14 weeks of age from 5,467 infants andPeripheral Blood Mononuclear Cells (PBMCs) bankedin liquid nitrogen to allow for future nested case-control studies comparing the immune response amongthose who develop TB with those infants who are ex-posed in the household and do not develop thedisease. Follow-up will continue through July 2006.

The overall Clinical Site Development Programmein South Africa was designed to characterize the TBproblem among neonates in the collaborating com-munities in the Western Cape region and to preparefor Phase III trials of new vaccine candidates. Amongthe lessons learned are that the surveillance may beimpacting on the measurement of the incidence oftuberculosis. Over 200 cases of culture and Acid FastBacilli (AFB) smear-positive tuberculosis have already

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been identified in this cohort with a 2.3% incidenceestimated during the first two years of life by a life-table technique. However, many of these cases areasymptomatic and have normal chest X-rays. All re-ceived a full course of four-drug chemotherapy so it isunknown whether these infants would have gone onto develop symptomatic TB disease or if the infectionwould have resolved on its own. Since TB occurrenceof tuberculosis disease is likely to be the primaryendpoint in a phase III study, it is important to resolvethe natural history of disease in infants and thereforeadditional studies are planned. Aeras also plans to con-duct a large cohort study among adolescents (12–18years old) in the same community to prepare for phaseII TB vaccine trials in this age group.

In addition, Aeras has collaborated with SouthAfrican colleagues to develop a Professional Develop-ment Programme that provides required backgroundon clinical research and a foundation for later trainingin protocol procedures. The programme is designedto meet the needs of adult learners and to be accessi-ble to the entire range of staff, including those wholeft school short of high-school graduation and thosewho may have bachelor or other college degrees.

Aeras has also undertaken a similar capacity devel-opment effort in India, working with colleagues in theInstitute of Population Health and Clinical Researchat St. John’s Medical College in Bangalore, India, todevelop a site in Palamaner District in Andhra Pradesh.Activities here will be partially funded by a recent US$3 million award from CDC in the US. Neonatal andadolescent cohort studies as similar as possible to thoseAeras is sponsoring in South Africa will be conducted,and the Professional Development Programme will alsobe implemented at this site.

Institute for OneWorld Health (IOWH)Moving from clinical trial to regulatory approval in disease-endemic countries■ To protect the health of citizens in disease-endemiccountries (DECs) where infectious diseases are ram-pant, it is critical to move a compound through clini-cal trials and the regulatory approval process as quicklyas possible. The challenges in doing so are many andinvolve demonstrating clinical effectiveness and safetyunder conditions which are frequently less than desir-able; finding a manufacturer, which can produce the

drug that is affordable by the patient; getting the drugapproved by regulatory authorities as soon as possible;and getting it distributed to a patient population, partof which may be located in isolated rural areas.

At the Institute for OneWorld Health, we are cur-rently developing an off-patent aminoglycoside anti-biotic that is no longer marketed, paromomycin, forthe treatment of visceral leishmaniasis. This drug isinitially intended for India and subsequently for otherDECs. Its development is very important to us, notonly because it can save hundreds of thousands of lives,but because it will show that our business model ofcombining foundation and charitable donations withina pharmaceutical company model, partnering withcompanies and organizations in the developing world,yields an effective pathway for developing pharmaceu-ticals for the treatment of infectious/parasitic diseasesin the developing world.

To meet the challenges we face, we are partneringwith charitable foundations, international health or-ganizations, pharmaceutical companies and NGOs. Ourstaff is composed of scientists and clinicians who havehad many years’ experience in drug development inthe international biopharmaceutical industry, as wellas chemical and manufacturing consultants, and regu-latory affairs consultants with international experience.

Our phase III paromomycin efficacy clinical trial,being conducted in India, is funded largely by the Bill& Melinda Gates Foundation. Our partner, WHO/TDR, is providing clinical monitoring. Paromomycinwill be manufactured at a cost patients can afford bythe International Dispensary Association of the Neth-erlands and its subcontractor, Gland Pharma, of Indiaaccording to the US Food and Drug Administration(FDA) good manufacturing practice (GMP) standards.Regulatory filings will be made in targeted DECs, ini-tially India. To enhance regulatory approval, we willwork closely with target DECs’ regulatory authorities,and are considering seeking orphan drug status andfast-track approval by both the European MedicinesAgency (EMEA) and the FDA, because DECs fre-quently approve drugs undergoing regulatory approvalby these agencies more quickly. Lastly, we will workwith NGOs to establish distribution mechanisms forgetting the drug to patients, as well as monitoring itsclinical use and effectiveness.

The success of this project will demonstrate how

partnering enhances the effects of participating organi-zations to bring a drug to DEC patients more quickly,potentially saving hundreds of thousands of additionallives.

International AIDS Vaccine Initiative (IAVI)Ensuring rapid access to preventive HIV vaccines■ AIDS is the greatest public health challenge of ourtime. Over 40 million people have HIV or AIDS andover 14,000 people are infected each day. Preventionprogrammes are helping to slow the spread of HIV,but there is an urgent need for improved and easier-to-use prevention technologies. Vaccines are amongthe most cost-effective public health technologies avail-able, and a safe and effective HIV vaccine would makea significant difference to current efforts to control theepidemic.

Once a vaccine is developed formidable barriers stillstand in the way of rapid global access. Historically,developing countries have waited an average of 15 yearsor more after new vaccines have been licensed in in-dustrialized countries before getting them themselves.This is clearly unacceptable – but to change it will takeproactive and coordinated action from governments,the private sector, international agencies and commu-nity organizations throughout the world. And this ac-tion needs to start now. With prompt action the worldcould use a preventive vaccine to avoid the inequitieswe now witness in HIV/AIDS treatments. Waiting toaddress access issues until after an HIV vaccine is li-censed will be sentencing millions to preventable ill-ness and death.

IAVI was established with the twin objectives ofspeeding the development of an HIV vaccine and ofensuring that when a safe and effective vaccine is de-veloped it is widely used in developing countries. Acrucial component of IAVI’s work lies in supportingthe development and implementation of policies toensure rapid access to HIV vaccines. In partnershipwith other stakeholders, IAVI is working to ensure thatthe necessary policies, mechanisms and infrastructurewill be put in place well in advance of a vaccine beinglicensed.

Among the challenges that IAVI believes need tobe addressed are:

1. Developing sustainable global financing and vaccinepricing mechanisms to ensure that vaccines arewidely available.

2. Minimizing delays in access by ensuring that thereis ample manufacturing capacity available to meetglobal demand at the time a vaccine is licensed.

3. Investing in the development and/or strengthen-ing of appropriate delivery systems, policies and pro-cedures for reaching adolescents, sexually activeadults and other at-risk populations.

4. Ensuring that there is ample clinical trial and regu-latory infrastructure to fast-track HIV vaccine clini-cal trials and to streamline and coordinate thelicensing of an HIV vaccine.

5. Supporting the development of regulatory skills indeveloping countries so that they have the capacityto review and approve HIV vaccines in a timely fash-ion for use in their own populations.

Product development partnerships:Still an evolving fieldThe foregoing outlines the early history of the not-for-profit product development ventures that haverecently emerged and illustrates their operations.

For the reasons outlined in the Preface, IPPPH andthe meeting co-organizers, the Bill & Melinda GatesFoundation; the Department for International Devel-opment, UK; the Rockefeller Foundation; and theWellcome Trust concluded that a critical review wouldbe warranted and hence convened the meeting on 15–16 April 2004.

The meeting showed that the field is dynamic. Everyfew months another interesting example is added tothe illustrations above about how product developmentpartnerships go about their respective missions.

The London meeting and this report of the state ofthe field of product development partnerships will un-doubtedly need revisiting periodically. The followingsummaries represent a first – and probably imperfect –attempt to survey an evolving field.


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Meeting summaryKatherine White

ent field, albeit with broad differences driven by theenvironment in which they operate. As product devel-opers for ‘neglected diseases’, or diseases of poverty,the PD PPPs share underlying similarities, as well asdiffering on many features and the context in whichthey operate.

Discussions during the meeting covered a numberof areas surrounding the current understanding of thePD PPP field and its future needs. The main themes ofthis discussion are summarized in the following sec-tions:

• PD PPP model• Key interfaces with other organizations• Role of portfolio management• Preparing for access: availability and adoption• Financing• Judging success• Role of coordination

PD PPP model4

There was general agreement that the PD PPPs are acoherent group and that the model is a sound approachto bridge the gap that has existed between basic re-search and the need for new products to control/com-bat diseases of poverty. Their activities are generallycharacterized by:

M E E T I N G S U M M A R Y

Background

Aworkshop “Combating diseases associated with pov-erty: Financing Strategies for Product Development

and the Potential Role of Public-Private Partnerships”1

was organized by the Initiative on Public Private Part-nerships for Health (IPPPH)2 in collaboration with theRockefeller Foundation, the Bill & Melinda GatesFoundation, the UK Department for InternationalDevelopment and the Wellcome Trust. Prior to theworkshop, IPPPH commissioned a comprehensive setof background papers to help prepare participants (seeannex 9). In both the background materials and meet-ing discussions, attempts were made to elucidate thesignificance of the many differences among productdevelopment public-private partnerships (PD PPPs) fortheir funding requirements and probabilities of success.

Participants at the meeting represented a broadarray of current and potential actors in the field fromthe PD PPPs, their funders, the private sector and otherconstituents.3

The workshop was organized around the followingfive objectives:

• Provide background on the emergence andoperations of the PD PPPs.

• Consider how PD PPPs and other players oper-ate and interact.

• Assess the current and future financial needs ofPD PPPs.

• Assess if innovative financing options for diseasesof the poor exist.

• Identify questions and issues requiring furtherattention and study.

Meeting discussion themesDuring the two days of discussion it became clear thatas a group, PD PPPs could be thought of as a coher-

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1 Held at the headquarters of the Wellcome Trust, London, UK,15–16 April 2004.

2 A component of the Global Forum for Health Research, es-tablished to monitor, analyse and support ventures in public-private collaboration to reduce global health inequitiesassociated with poverty.

3 For full list of participants see annex 2.4 See annexes 9b (Sander A, Widdus R. The emerging landscape

of public-private partnerships for product development) and 9l(Ridley R. PD PPPs for diseases of poverty. Are there moreefficient alternatives? Are there limitations?).


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• A focus on product development for diseases ofpoverty.

• Use of private sector management practices in-cluding portfolio management and industrialproject management.

• Advocacy for their own work and often forglobal attention to their disease(s) of interest.

However, there was also recognition of the differencesin approach across PD PPPs as a result of:

• Technical differences in drug, vaccine, microbi-cide and diagnostics/device development.

• The extent to which individual PD PPPs haveimplemented portfolio management.

• The specific context in which an individual PDPPP is operating, including scientific developmentand political will associated with the disease(s) offocus.

One challenge is to communicate the core strengthsand perceived benefits of the model with simple mes-sages that cut across the entire field of PD PPPs toencourage a broader support base (see also subsectionon financing, below).

PD PPPs are not an end in themselves but are apractical way to help address a specific public healthinequity that characterized the 1990s: the near-totallack of development of essential new products for thediseases of the poor. In particular the use by PD PPPsof portfolio management is a key distinguishingfeature of this new field, very different from the linearapproach to vaccine and reproductive technologydevelopment that has sometimes been pursued by thepublic sector in the past. On their own PD PPPs arenecessary but not sufficient to address the global healthneeds outlined in the Millennium Development Goals.1

Each pursues its own strategy, driven by the eco-nomic and social context in which they are operatingto ensure development and access to its products. Thisaffects every decision point along the product devel-opment pipeline from acquisition of candidate prod-ucts, to the choice of manufactures, to the need forstrong partnerships with donation programmes, pro-curement programmes and/or other ‘pull’ mechanismsto ensure the neediest and poorest populations around

the globe benefit from the products that result fromthe PD PPPs efforts.

Open questions■ Should the PD PPP field continue to proliferate or

have the most important opportunities already beenaddressed?

■ How should funders balance their investments inPD PPPs with other approaches to product devel-opment (e.g., funding the private sector directly, orfunding individual projects)?

■ How should funders balance investments inaccess to existing products with investments in newproduct development?

■ What is the right balance of public and private sec-tor goals, staff and managerial approaches for thePD PPPs? How will this vary as the PD PPPsmature?

Key interfaces with other organizationsWithin the commercial world of product development,effective management of interfaces with other compa-nies and institutions is critical for success. Due to thecross-functional nature of the development processthere is an increasing emphasis on the complexoutsourcing networks throughout the R&D con-tinuum. The private sector also benefits from thefocus and essential discipline instilled by a commercialmarket, in which success is easily quantified by thebottom line.

Traditionally for big pharmaceutical companies,many of the connections that need to be made areinternal. In pre-clinical development, for example, in-house chemists, biologists and toxicologists must worktogether to determine a target molecule’s suitabilityfor progression to clinical trials. This is not the case forPD PPPs.

Most PD PPPs, like many biotech firms, are rela-tively small and achieve a large portion of their workthrough others, by connecting the requisite people,communities, organizations and companies to achievetheir goals. Depending on the state of the science andthe nature of the products and disease targets, thefocus of activities along the spectrum from research todevelopment to access may vary. Whatever role a PDPPP itself takes on, effective management of interfaceswith, and “hand-offs” to, others remains central to its

1 See annex 5 (United Nations Millennium Declaration, UnitedNations Resolution 55/2 2000).

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strategy. Since product development is at the core ofall PD PPPs, interfaces with the following players wererecognized as important to all PD PPPs:

• Disease-endemic countries (DECs)• Public sector• Private sector

Disease-endemic countriesDisease-endemic countries already provide valuablecontributions to product development all the way fromresearch to end product delivery and use. IncreasingDEC involvement will help build ownership of poten-tial products and increase the potential for successfuldelivery and adoption of new products.

As discussed above, there may be further opportu-nities to link directly investment in basic research andsystem strengthening in these countries with the workof the PD PPPs. The DECs are also integral to threeother components of the development process, pro-viding the end-user perspective, clinical trial capacityand in preparation for access.

End-user perspectiveDeveloping drugs and other products that will be usedand embraced by those in need requires early consid-eration of their needs and perspectives. Within bothbig pharmaceutical and biotech companies, the involve-ment of their commercialization groups (those withthe greatest customer insight) begins early in the proc-

ess as the candidates’ transition into pre-clinical andclinical development. It is just as important for PD PPPsto get the same kind of market input; a product has novalue if it is not used. Many of the PD PPPs are alreadygetting some involvement through their boards,scientific advisory bodies and through sophisticatedmarket analyses. It was very clear that involvement ofthe ultimate customers and generating ownership atthe country level is integral to success and is not anoptional extra.

Basic researchThere was a strong feeling during the discussions thatin the longer term research from DECs could play animportant role in contributing to the overall successof the PD PPPs. In the shorter term, one idea to in-crease the flow of leads that was discussed was strength-ening the links between PD PPPs and existing researchcommunities in disease-endemic countries. Anotherarea of discussion included the potential for traditionalmedicines, widely used throughout Africa, China andSouth-East Asia, to provide an additional source ofpotential candidates.

Today, while there may be applicable research, thesecommunities often do not have strong technologytransfer skills. It may be beneficial to go further thancreating direct links to PD PPPs by setting up centresof excellence around specific disease areas in some coun-tries. Centres of excellence could help provide the criti-


PUBLICSECTOR

PRIVATESECTOR

DECs Localcommunities

DEC basicresearch capacity

DEC clinicaltrial capacity

In countrypolicy makers

Public researchcapacity

(e.g. national laboratories)

National and internationalpolicy organizations

(e.g. WHO, EMEA, FDA, etc.)

Big pharma, biotech and contractresearch and development companies

End-userperspective

Basicresearch

Clinicaldevelopment Delivery

Potential interfaces for PD PPPs along the development chain


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cal mass and focus characteristic of successful researchgroups in the commercial drug world and would pro-vide a natural interface point for linking into specificPD PPPs. It could also have the added benefit of bring-ing the local ‘customer’ (or intended beneficiary) per-spective into the development process earlier andbuilding research capabilities in these countries. It wasgenerally agreed that PD PPPs should not be expected,as a principal goal, to address the need for researchstrengthening in disease-endemic countries.

Clinical trial and regulatory capacityEffective clinical trials require physical sites, ethical re-view capacity and the appropriate regulatory bodies tosupport the trial and ultimately approve the productfor use. In sub-Saharan Africa, where many of the prod-ucts will need to be tested, there is a shortage of allthree. Bridging this gap will require scientific and regu-latory leadership as well as significant investment infunding.

• Trial sites: With more than 3001 products for‘neglected diseases’ in development globally thereis not the trial capacity to support the current pipe-line. In response many groups are independentlyinvesting in trial site capacity (e.g., individual PDPPPs and the European and Developing CountriesClinical Trials Partnership [EDCTP]). Given thehigh cost of such investment there may be benefitsfrom increased coordination in this area where pos-sible. Once established it will also be necessary toensure a steady flow of projects to sustain them. (Seealso IPPPH 2004.2)

• Regulatory capacity: In many of the countries wheretrials could be conducted, there is limited local regu-latory capacity to provide approval for such trialsand successful products. While trials can be rununder the guidelines from other recognized regula-tory bodies (e.g., the United States’ Food and DrugAdministration [FDA]) the absence of such capac-ity is one of the reasons many industry players choosenot to run trials in these countries.

• Ethical review capabilities: Credible research cannotbe conducted anywhere without two review capa-bilities: the ability to gain informed consent; andthe presence of effective ethical review committees.While committees are being established they are

often of poor quality due to the limited training andawareness of international standards.3 In cases whereresearchers work with an international InstitutionalReview Board (IRB), the board may not be as sen-sitive to the issues raised by the local culture4 (e.g.,the need for consultations with families and com-munities). Local researchers need to be trained sothat they can play a role in determining the natureand type of ethical guidelines used in internationalcollaborative research.

For sub-Saharan Africa, one of the options discussedwas to develop capacity in a representative set of Afri-can countries; balancing the potential benefits of focuswith the benefits that capacity building in a broaderset of countries could bring. However, increased DECinvolvement in product development cannot be thelone burden of the PD PPPs (e.g., capacity buildingfor research, regulatory infrastructure, etc.). While itis clear that PD PPPs will need to work closely withdeveloping countries in this area, leaving the task tothe PD PPPs would risk losing the focus that they bringto the product development. A challenge for the PDPPPs is how to leverage their collective voice to facili-tate increased focus and momentum from organiza-tions such as WHO, which can help by working inparallel with them.

In the future it might be possible to see some PDPPPs basing themselves in DECs. However, this isunlikely while R&D and innovation primarily occursin developed countries.

DeliveryDisease-endemic countries will also play a critical rolein working with the PD PPPs to ensure access anddelivery of the products that are developed. See sub-section Preparing for access: availability and adoption,below.

1 See annex 9h (Kimanani E, Clements V. Current status of clini-cal trials in Africa).

2 IPPPH. 2004. Clinical Trial Capacity in Low Income Coun-tries: Experiences, lessons and priorities for strengthening.

3 See annex 9g (Leke R. Ethical review capacity: Country needs,role and responsibility of partners and researchers).

4 “83 per cent of the developing-country researchers surveyedcriticised US IRBs for being insensitive to local culture” Ethi-cal review of health research: a perspective from developingcountry researchers, Hyder et al. J Med Ethics. 2004.

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Public sectorBasic researchPD PPPs have three primary sources of product con-cepts for drug development:

• Development or modification of an establishedproduct for new indication(s).

• Continued development of previously abandonedproducts (often abandoned due to lack of com-mercial market).

• Development of totally new products.

Development of totally new drugs requires novel prod-uct concepts or leads from the basic research commu-nity (e.g., academic laboratories) to be fed into theproduct pipeline. ‘Translation’ is the term used to de-scribe this transfer from basic research into productdevelopment. Ensuring that a flow of high-quality ideasare translated into products requires clear communi-cation of the target product you are trying to develop,as well as awareness in the research world of how tochannel ideas into PD PPPs or other developmentmechanisms.

In recent years there has been a significant increasein the flow of leads from basic research into commer-cial drug development. Universities and other researchinstitutes are paying more attention to the benefits theycan reap from successful translation of their researchwith many employing technology transfer managers.While there is often funding of basic research for mostof the neglected diseases being targeted, there is still astruggle to translate this investment into potentialmedicines. From the discussions during the meetingtranslation efforts today appear to be facing two mainchallenges: scarcity of practical product-directed re-search; and the mechanisms to flow potential leads intoPD PPPs.

For most academics working in research there is lit-tle incentive to focus on practical product-directed re-search when credits and accolades are more prevalentfor basic research. Given that academics are primarilyjudged on the number of publications they produceand how much grant money they bring in, fundingorganizations could play an important role in chang-ing some of the incentives. They could help make itattractive for PhD students and academics to push re-search until product developers can adopt it. For mostof those funding basic research today this would re-

quire an increase in understanding about the impor-tance of translation and the process.

Even where there is a high level of awareness of thebenefits of technology transfer and there are potentialleads or candidates that could be applied to neglecteddiseases, many of the technology transfer managers arenot aware of the public health impact they could behaving. There may be opportunities for themproactively to include intellectual property clauses intheir agreements to ensure potential applications forneglected disease are not lost. For example, Yale Uni-versity recently licensed a compound for commercialdevelopment for athlete’s foot and reserved the rightsfor any indications in support of Chagas disease. Tech-nology transfer in universities is largely driven bymetrics, such as numbers of patents licensed and in-come to the universities, raising the question of howto encourage consideration of public health issues aswell as raising awareness of the routes into global health.

Even if promising leads are generated and identi-fied there is the challenge of translation itself. In manycases the skills and resources needed to help ensuresuccessful translation reside largely within the privatesector (e.g., development of assays, compound librar-ies, production scale-up, development of analogues,medicinal chemistry, etc.). Many PD PPPs are alreadyworking with subcontractors or negotiating in-kindcontributions from the pharmaceutical industry to helpenable the flow of novel product-focused leads intothe pipeline, but more attention in this area is still re-quired.1 There was strong feeling during the workshopthat any investment and capacity building to improvetranslational capabilities should pay equal attention toopportunities in both the developing and the devel-oped countries.

For the future of the field it is imperative to increaseawareness and the level of investment in product-fo-cused research and translation mechanisms. Without asteady flow and successful translation of potential leads.the PD PPP model will not be sustainable.

Clinical development, regulatory approval and deliveryMuch of the work the PD PPPs do to develop andmanufacture new products requires either approval


1 See annex 9f (Nwaka S, Widdus R. The current research-to-development ‘Hand-off’ process for product concept/candidateproducts and possible improvements in it).


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from existing regulatory authorities (e.g., FDA and theEuropean Medicines Agency [EMEA]) or, where avail-able, from country regulatory bodies. As discussedabove, in many of the countries for which the prod-ucts under development are intended, there is not suf-ficient regulatory capacity. As a result PD PPPs mustwork within existing regulatory frameworks whichoften have a very different risk benefit threshold. Inother cases, such as microbicides, the existing regula-tory bodies do not have the necessary experience inapproval and registration of the class of products. Dur-ing discussions at the workshop there was strong feel-ing that coordination amongst PD PPPs and thoseorganizations supporting them could help increasepressure on existing bodies to address the desperateneed for regulatory harmonization and simplification.

As the PD PPPs plan for the success of their devel-opment efforts, they must also work in parallel withother organizations and groups to ensure that publicpolicy, financing and infrastructure are ready once aproduct has been successfully developed.1 Many of thegaps in resources or capacity highlighted during theworkshop’s discussions could be addressed throughexisting public sector organizations (e.g., WHO, UNand bilateral organizations). In particular some of thecapacity building (e.g., translational capabilities, regu-latory capacity, delivery infrastructure, etc.) and sys-temic issues (e.g., rapid public policy formulations,regulatory harmonization, etc.) are already within theremit of these organizations. The issue appears not tobe one requiring new organizations but an increase infocus and attention on the issues. (See also subsectionPreparing for access: availability and adoption, below.)

Private sectorMany of the skills required by the PD PPPs – bothnow and, increasingly, in the future – lie within theprivate sector. While many PD PPPs have links to pri-vate industry there was strong agreement that increasedprivate sector involvement would be beneficial. Theprivate sector today has been a source of both candi-date products and access to technical expertise andphysical resources, areas that will continue to be im-portant in the future. Examples include:

• New research technologies: While the exact ben-efits are not yet clear technologies such asgenomics or platform technologies should offeropportunities to improve the quality and flow ofleads.

• Manufacturing: Formulation, scale-up, qualitycontrol.

• Regulatory: Management of the process of sub-mission and reviews.

• Market assessments: Market sizing and economics.• Post-launch activities: Pharmaco-vigilance, prod-

uct liability.• Intellectual property.

A better understanding of the current barriers to pri-vate sector participation is required if the level of in-volvement is to be increased significantly. Historicallyone of the greatest barriers to greater involvement, inaddition to the opportunity cost, has been reputationalrisk given the political nature of the diseases and set-tings involved. Among some of the workshop partici-pants, there was a strong belief that such an increasewill only come from top-down support, driven by chiefexecutive officers or senior research officers.

While big pharmaceutical companies have many ofthe significant expertise and physical resources required,the biotech community also offers a valuable source ofresources. The biotechs may not have all the resourcesof big pharma available but they are likely to have dif-ferent opportunity costs than their larger counterparts.The private sector could have several motivations forgetting further involved with PD PPPs, starting froma humanitarian desire to do the right thing, opportu-nities for good public ‘image’ and the benefits thatcome from people in the company feeling good aboutwhat they are doing. However, their involvement needsa good business case, as private companies must ulti-mately satisfy their investors. One of the challenges forPD PPPs is to encourage the private sector to articu-late what it will take to get them involved and to ex-plore innovative ways to work together.

One promising area of opportunity is innovativelicensing agreements with the private sector. This isespecially the case in instances where a private drugcompany has already started the development of aparticular product for which there may be both a com-mercial and a public health market, but where the

1 See annex 9i (Ghosh G. Emerging lessons in preparing for up-take of new vaccines).

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development risks outweigh the potential commercialbenefits to the company. PD PPPs are already benefit-ing from licensing high-potential products in such away as to ensure technical support in conjunction withthe product while reserving the benefits from poten-tial commercial applications for the private company.The recent deal between the International Partnershipfor Microbicides and Tibotec (affiliated with theJohnson & Johnson companies),1 is just one exampleof the types of deals PD PPPs for both infectiousdiseases and contraceptives have been able to reach.2

The biggest opportunity, however, is to build mar-kets where companies can expect a reasonable returnfrom their investment (e.g., through pull mechanismsand/or tiered pricing structures).

Open questions■ What is the right balance for PD PPPs between get-

ting the product development done and ensuringupstream and downstream gaps are filled?

■ What will help ensure that links between the PDPPPs and different sources of research in their fieldare strengthened? What are the best opportunitiesto strengthen links with research in disease-endemiccountries?

■ How could the development of research centres ofexcellence aligned with specific diseases be encour-aged?

■ Could incentives for facilitating action be put in placeto make it attractive for PhD students and academ-ics to push research to the point where it could beadopted by product developers?

■ Can more be done to increase awareness amongtechnology transfer offices of potential routes intomeeting global health, as well as commercial,opportunities?

■ How can issues of clinical trial, regulatory and ethi-cal review capacity be handled to address the needsof the PD PPP field?

■ What will it take to capture the attention of seniormanagement within the private sector and thus in-crease their involvement with and support of PDPPPs?

■ How best to increase speed and focus of publicsector organizations on critical path investmentsthat will facilitate successful development andintroduction of drugs, devices and vaccines? Can

PD PPPs articulate their needs and priorities collec-tively?

Role of portfolio managementMany meeting participants familiar with product de-velopment repeatedly emphasized the length and theriskiness of the process, with attrition of candidate prod-ucts expected at every stage along the research-devel-opment-access (R–D–A) continuum.3 Portfoliomanagement evolved in the private sector as a vitalprocess by which to limit risk, manage the flow of prod-ucts to market and minimize the cost of the drugdevelopment process.4 Portfolio management has twokey components:

• Diversification to reduce the reliance on a smallnumber of candidates with similar characteristicsand to ensure that the flow of products throughthe pipeline is smooth (i.e. enough products atdifferent stages of development).

• Rigorous processes to ensure candidates that donot meet the specifications are weeded out.

Since most product candidates will fail somewherealong the development pipeline, management of mul-tiple candidates helps to insulate funders from the risksinherent in health product development. The successof portfolio management is also highly dependant onthe quality of the leads fed into the pipeline, reinforc-ing the importance of effective translation from researchto development for PD PPPs. The availability of theright human resources and skills to ensure the processis run effectively is just as important for the PD PPPsas it is for the private sector.


1 Under the arrangement, Tibotec provides a royalty-free licenceto IPM to develop, manufacture and distribute TMC120 as amicrobicide in resource-poor countries. Tibotec has alreadydeveloped a TMC120-containing gel, which is currently inphase I clinical testing. IPM will assume responsibility fordevelopment of this compound. Under the agreement, Tibotecwill bear the cost of the compound through phase II testingand will remain active as a scientific advisor. IPM Press Release,29 March 2004.

2 See Kettler H, White K. 2003. Valuing Industry Contributionsto Public-Private Partnerships for Health Product Development,IPPPH, and other examples in the full version of this report.

3 See annex 9f (Nwaka S, Widdus R. The current research-to-development ‘hand-off’ process for product concept/candidateproducts and possible improvements in it).

4 See annex 9d (Schmid E. Portfolio management in the phar-maceutical industry).


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Level of portfolio managementA number of times during the workshop, discussionsfocused on the different levels at which portfolio man-agement could be conducted within the PD PPP field.Portfolio management could in theory be done at sev-eral levels by different players:

• Across the various diseases of poverty (neglecteddiseases) and across PD PPPs, by funders actingin coordination.

• Across a disease area, by a PD PPP.• Across the array of products being developed by

a particular PD PPP.

One of the challenges of operating portfolio manage-ment across the various neglected diseases and acrossPD PPPs would be how to implement the process effi-ciently to ensure timely and effective decision-making,which would be respected by all parties involved. Simi-larly it is unlikely that a single PD PPP would everhold sway across all development in a particular dis-ease area. However, some PD PPPs today chose toprioritize and select candidate products for develop-ment in light of those products already under devel-opment in their field; thus helping to reduce thedevelopment risk within a particular disease/productarea.1 Other PD PPPs are applying the principles ofportfolio management to the array of products theyare developing or have direct influence over.

The general conclusion of the discussions was thatfunders need to be in a position to support the portfo-lio management process and its outcomes but that PDPPPs are best placed to run the portfolio managementprocess. Many individual donors do not have the depthof technical and scientific knowledge needed to choosewinners and losers from among dozens of competingproposals. Most PD PPPs have explicit policies affect-ing portfolio turnover, with ‘go-no-go’ decisions takenby world-class scientific advisory boards and PD PPPtechnical staff. Thus the PD PPPs provide a way forfunders to ‘outsource’ these decisions to technicalexperts.

Scale for portfolio managementMany PD PPPs are still in the early stage of develop-ing their portfolios, falling well below the flow of prod-

ucts that would statistically be required to ensure ‘suc-cess’. From the work so far and the discussions duringthe meeting it is not clear what threshold for mini-mum scale or optimal functioning is required for port-folio management to be most effective. There wasconcern that to achieve scale there may be incentivesto include leads of lesser technical merit or reluctanceto kill projects in the pipeline for lack of better alterna-tives, thus reducing the overall potential for success.However, there was recognition that a rigorous proc-ess, with criteria agreed prospectively, can help improvethe objectivity and quality of decision-making, one ofthe cornerstones of the PD PPP model.

To understand effective portfolio management witha smaller number of candidates (as seems a necessity inthe vaccine field for practicability), it may be valuableto look at what the biotech field is doing in this area.In the case of some of the vaccine PD PPPs (MVI andIAVI), which have a portfolio of candidates against thesame disease target, there may be less opportunity tolearn from industry (the norm in industry is to havemultiple candidates against different targets). The ben-efits from a portfolio with multiple candidates focusedon the same disease target come more from the les-sons and knowledge transfer across the portfolio.

It is also worth noting that in many cases, while aPD PPP may determine which candidates are the mostpromising to meet a particular need, this does notalways mean the PD PPP will be directly responsiblefor the development of the selected candidate. Depend-ing on the context in which they operate and the avail-ability of suitable partners a PD PPP may outsourceeither in part or completely the development of theprioritized candidate product(s).

Target product profilesEstablishing agreed target product profiles (TPPs) is acommon tool used in portfolio management to facili-tate communication and expectation-setting along thedevelopment pipeline and to help to ensure that allrelevant parties have input (manufacturing, end users,etc.).

In general, TPPs include ideal and minimum crite-ria across a range of dimensions that reflect the cross-functional nature of product development. The criteriago beyond scientific potential to include usability,manufacturability, costs, time to market and market

1 See annex 9b (Sander A, Widdus R. The emerging landscape ofpublic-private partnerships for product development).

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potential. By defining success prospectively, and earlyin the process, progression or ‘kill’ decisions are stream-lined at a later stage. PD PPPs (in consultation withtheir disease-control counterparts) are ideally posi-tioned to play a role in developing target productprofiles for their diseases. TPPs can be used to solicitsubmissions in open calls for candidates or as a screen-ing tool for looking at in-licensing opportunities.

Managing the development of the profile and en-suring input from all the relevant stakeholders arealmost as important as developing the profile; a goodprocess is the best way to ensure a good profile. Theprocess of portfolio management and TPPs are wellestablished in many big pharmaceutical companiesoffering another potential area where industry couldhelp with resources or know-how.

Valuing products in a PD PPP environmentIn the private sector, products enter the pipeline at allstages of development. Capital markets and financialtools facilitate determination of a ‘value’ for productsand thus allow seamless comparison of in-house can-didates and external opportunities. Across the PD PPPs,portfolios of products have evolved very differently,coming from basic research, previously abandonedprivate sector candidates or existing products beingconsidered for a new use. Ascribing monetary value tothese products is not particularly valuable given therelative lack of a commercial market for products inthe PD PPP world. Given that the common goal ofPPPs is public health impact, it seems desirable that anapproach be developed to express the potential ben-efit of the anticipated products, taking into accountfactors such as:

• Cost and likelihood of successful development.• Target population and the fraction likely to be

reached.• Cost of ensuring ‘access’.

Funders and portfolio managementPD PPPs have a further challenge when executing port-folio management given the direct involvement of manyof the current funders of PD PPPs. A PD PPP thatwants to kill a project not only has to say “No” toresearchers but also sometimes to funders. In manycases, funders are not currently aligned with a portfo-lio of products but fund individual products or

projects.1 Many organizations providing funding to-day and in the future are not going to be familiar withdrug development, the long time frames and the highlevel of failure during development (a 95 per cent fail-ure rate is the norm2,3) putting PD PPPs in the role ofeducator and manager of expectations.

The general conclusion during the discussions wasthat funders should probably let PD PPPs manage thescience advice and the portfolio process.

Open questions■ Are there best practices for successful portfolio man-

agement in big pharmaceutical companies and thebiotech industry that would be applicable for PDPPPs, including those developing vaccines?

■ Are PD PPPs big enough to achieve the benefits ofeffective portfolio management? At what scale isportfolio management most effective?

■ Are funders willing to align themselves with a port-folio of product candidates rather than specificprojects?

■ Do PD PPPs require specific resources and capa-bilities to support portfolio management (e.g., port-folio models for vaccine candidates)?

Preparing for access: availability and adoptionNo drug, vaccine or device will be effective even if it isaffordable and of high quality if it does not reach thosefor whom it is intended. Ensuring access, availabilityand wide adoption is as much of a challenge as thedevelopment of the technologies themselves. Publichealth experience has shown that uptake of new tech-nologies is not always automatic (e.g., hepatitis B andantiretroviral drugs).

The term ‘access’ is often used to describe a varietyof different issues associated with the development ofproducts targeting the diseases of the poor, rangingfrom public policy to end-user product acceptability.While there is no commonly agreed definition for thepurpose of these discussions, two broad categories ofissues will be considered under the umbrella of access:availability and adoption.


1 See annex 9b (op. cit.).2 See annex 9a (Towse A, Mestre-Ferrandiz J, Renowden O.

Estimates of the medium-term financial resource needs for de-velopment of pharmaceuticals to combat ‘neglected diseases’).

3 See annex 9l (op. cit.).


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The work to ensure access needs to be started inparallel with the product development process to en-sure that the demand, public policy, financing and in-frastructure are all in place when a product issuccessfully developed.1 There was a general feeling thatPD PPPs need to embrace these issues but that theymay not necessarily be the best group to address all ofthem directly. However, PD PPPs may be able to playa role in defining the conditions required to support/ensure access.2 Critical steps in preparing for access(beyond the fundamental tasks of appropriate designfor disease-endemic countries and user acceptability)include the development of:

• Ensuring availability requires:— Appropriate regulatory approval and licens-

ing infrastructure— Manufacturing capability and sufficient ca-

pacity— Logistics and delivery networks in-country.

• Ensuring adoption requires:— End-user awareness about the product and

its benefits— Effective pricing and financing mechanisms

to ensure affordability— Supportive social and policy environment

(and the research to generate this).

Planning for availability and adoption will take signifi-cant investment, which is often neglected. For exam-ple, in the case of vaccines accurate uptake curves basedon product profiles and projected prices are requiredfive years before licensure to ensure capital investmentin properly sized factories to prevent tragic delays inavailability.3

At a macro level the leadership in DECs needs tobecome champions of health issues for long-term suc-cessful adoption of these products. Countries wherethe most progress is being made in tackling diseases ofpoverty have significant leadership from the top (e.g.,introduction of vaccines in Mozambique and the roll-out of new anti-malarial treatments in Zambia).

Open questions■ What role can current funders play in mobilizing

required resources to ensure delivery systems are inplace?

■ Who is best placed to build the evidence to influ-ence policy as these new technologies are developed?What evidence will be required?

■ How involved should PD PPPs be in the tasks asso-ciated with preparing for access? Who should be tak-ing the lead? If the private/governmental sector isnot fulfilling their responsibilities, who can holdthem accountable?

■ How can the attention of the leaders in disease-en-demic countries be captured?

FinancingAs one of the chief executive officers of a PD PPP whoattended the workshop put it “Our job is balancingtime and resources to do whatever is necessary to bringa product to market.” Whether done privately or inthe public domain drug development is expensive.When we are also talking about enabling access anddelivery for these drugs in developing countries wherethe mechanisms and policy are not yet in place, ex-pected costs rise even higher.

PD PPP needsA steady flow of funds or a significant amount of moneyin the bank is important to operate the daily activitiesof the PD PPPs and give them credibility. One of themost important tasks for PD PPPs is attracting humanresources to do the work. Unlike a start-up biotech aPD PPP cannot offer the necessary significant finan-cial incentives like talent stock options, making the sta-bility of funding very important. Having a strong bankbalance also helps ensure PD PPPs are taken seriouslywhen they negotiate with potential collaborators fromindustry. Companies that work with PD PPPs want toknow that if they start projects there will be financingto complete them.

One of the challenges faced by PD PPPs is that un-like a venture capital firm which invests in a biotechfor an agreed expected return, many of today’s fundershave not defined what they are looking for when in-vesting (e.g., absolute public health impact versus im-pact for the poorest social groups). A venture capitalfirm investing in a start-up biotech would also want a

1 See annex 9i (op.cit.).2 PD PPPs may also be able to work with access PPPs in fields

where they have been established.3 See annex 9k (Sadoff J. The Cost of Trials and Manufacturing

Process Development for Vaccines).

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good understating of the likely scale and timing of thepotential funds required; such clarity is not yet avail-able to funders of PD PPPs.

There was some discussion about the timing withwhich funds are disbursed to PD PPPs and the meritsof incremental year-by-year funding versus lump-sumcommitments that represent several years of funding.There was recognition that the larger lump sums bringincreased flexibility and credibility but that in practicalterms incremental funding was much more likely. Itmany cases the incremental approach is not very sys-tematic and comes in dribs and drabs from differentgrants and different funding processes. As the size andcomplexity of the financial commitments being madeby the PD PPPs increases, so too will the importanceof understanding the achievements/metrics requiredfor receiving additional support.

Current situationBased on estimates of funds committed by early 2003,and cost estimates for the portfolio of products under-way, the financing shortfall through 2007 for majorPD PPPs appears to be at least US$ 1.2 billion andpossibly over US$ 2.2 billion, depending on assump-tions.1 There was strong agreement about the severityof the funding gap, if not its exact size, and concernsthat the current base of funders may not be sufficientto sustain the existing array of early candidates and PPPsas they mature.

Today’s best estimates of the funding gap are basedlargely on estimates of development costs by phase ofdevelopment and expected failure rates for differentphases of development based on historical experience.In some, possibly most, situations the cost of deliver-ing the drugs could significantly exceed the productdevelopment costs. During the meeting a strong de-sire was expressed to expand this work to provide aneven clearer picture of the funding gap. Areas that couldbenefit from further clarification and inclusion in suchan analysis include:

• Attrition rates by phase of development,2 particu-larly for newer vaccines.

• Cost of development by stage (see annex 9a).

• Investment in capacity required (e.g., clinical tri-als, manufacturing facilities, etc.).

• Preparation for access (e.g., research to influencepolicy, delivery systems, etc.).

• Timing of the required funds.• Variation in the above factors across drugs,

vaccines, diagnostics and other products.

While in-kind contributions are recognized as an im-portant resource to the field that is likely to continue,quantifying their value is particularly hard given theunpredictable and sometimes intangible nature of thesecontributions.

Broadening the funding baseToday the majority of funding for the PD PPPs comesfrom bilateral organizations and philanthropic foun-dations focused on development and public health. Insome cases PD PPPs are still supported by a single, orvery preponderant funding source. The Bill & MelindaGates Foundation is the sole or major funder in FIND,MVI and HHVI. The sheer weight of future invest-ment required makes it essential for the field to gener-ate support from beyond these traditional funders,which have many competing demands on their re-sources. On top of this there is growing concern thatthe growth of the field is stretching the human re-sources of both existing funders and the PPPs with theamount of time spent on educating and lobbying forfunding. In addition many of these funders are work-ing to meet the needs of getting existing technologyto people today.

Broadening the funding base beyond traditional‘development’ funders will require a focused advocacyeffort for both the PD PPP model and investment inproduct development. Neither traditional funders norpotential funders have historically invested in this typeof product development and may not be able, at thispoint, to grasp the real significance of candidate fail-ures or the magnitude of the investment required. Formany there will be the question of the trade-off be-tween investing in getting existing products to peopletoday and investing in R&D for new products. Theincreasing use by PD PPPs of more business-case styleanalysis that starts to look at return on investment (bothpublic health and monetary) will help funders assessthese trade-offs. The more sophisticated and practisedthe PD PPPs become at these analyses, the better they


1 See annex 9a (op. cit.).2 Including differences between small-molecule drug and vac-

cine development.


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will be positioned to obtain financing from any source.While PD PPPs are not the only vehicle for productdevelopment, the model appears to be very well adaptedto generating in-kind contributions and support fromboth the private and the public sectors. Analysis byimpartial commentators concluded that the PPP ap-proach, while needing some refinements, is currentlythe main hope for progress.1

The good news is that there are still many globalplayers who are not actively supporting investments inproduct development (e.g., not all members of the G8).However, as discussed earlier, any strategies to increasesupport will only be successful with clear, simple mes-sages about the benefits and public health outcomesthe PD PPPs aim to deliver and why the model is ad-vantageous. For some of the smaller governments andfunders, which do not have the capacity to assess eachPD PPP investment opportunity, efficient mechanismsto get them involved will be important. Within theprivate sector there could also be opportunities to getsome of the multinational companies involved.

Innovative strategiesOther ways to address the funding gap include explor-ing other financing mechanisms to attract new fundsand looking for potential cost-saving strategies.

FinancingThe World Bank’s ‘Out of the Box’ working group2

has, as part of its remit, been looking at opportunitiesto leverage the capital markets to attract new fundersor optimize existing financial flows.3 Some of themechanisms allow funds promised in the future to bebrought forward in time (tax exempt debt andsecuritization); others could bring new capital (projectfinance and put options4). In general, while thesemechanisms may be applicable in a small number ofsituations (e.g., project financing to help enable in-vestment in manufacturing sites), they are unlikely toattract significant amounts of new capital to productdevelopment per se.

‘Pull’ mechanisms, including guaranteed purchase,could also benefit the PD PPP field. These mechanismsreduce risk to the developers by providing assurancesabout the future market for the products under devel-opment. Recent work by the Pull Mechanisms Work-ing Group5 has shown that these mechanisms are legally

and practically feasible and enforceable, which will in-crease their potential as a tool for the market. A pointmade by several groups at the meeting was that ‘pull’mechanisms alone will not be sufficient to tip the bal-ance and open the doors to private investment in thesemarkets.

There was also discussion about the potential toencourage more private sector involvement by reintro-ducing the profit motive. While this is not a newstrategy in itself, some of the drug manufacturer rep-resentatives highlighted concerns about possiblepolitical and negative public relations ramifications ofprofiting from diseases affecting the poor.

Cost reductionWith such a large amount of funding required, theobvious question of what opportunities exist to reducethe overall requirements must be explored. One of thedrivers of cost in the process of developing and gain-ing approval for a product is the regulatory environ-ment. There could be opportunities even within thecurrent regulatory framework to reduce the burdenon phase III trials and perhaps shift some of the workinto a phase IV study so that the costs are only in-curred if the product is successful.

With some of the later-stage, larger investments,there may also be opportunities for cost savings fromsharing resources or investments across PD PPPs, forexample development of clinical trials or manufactur-ing capacity.6 Other strategies could involve shiftinginvestments to lower-cost countries. However, therewas some concern that benefits might not be that sig-nificant; for example, one comparison of manufactur-

1 See annex 9l (op. cit.).2 Assembled by James Wolfensohn, President of the World Bank,

the group consists of senior leaders from industry and the publicsector, with particular focus on representation by finance pro-fessionals specializing in health care.

3 See annex 9c (Batson A, Shah R, Gingerich C, Rosenquist JN.PPPs and product development: Innovative financing opportu-nities and the need for a ‘business case’ approach).

4 A put option is a contract that gives the holder a right to sell acertain asset to the writer of the option at a specified price upto a specified date.

5 See annex 9i (Ghosh G. Emerging lessons in preparing for up-take of new vaccines).

6 Shared manufacturing facilities are not a possibility for vaccinesas current regulations essentially preclude multiple use facto-ries for large scale production.

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ing plant costs bewteen India and New Jersey, USA,suggested less than a 20% saving.1

Open questions■ What is the true funding gap? How much is required

and when?■ Who are other potential funders and what con-

straints/goals influence what they can fund?■ Is there more to be done to garner support from

the countries for which these products are destined?■ What role can existing funders play to help attract

additional funders?■ What is the right funding balance between PD PPPs

and other product development models?■ How to ensure balanced funding for research, trans-

lation, product development and uptake?

Judging successMany of the PD PPPs have established a set of internalmetrics to monitor their own performance. However,there does not appear to be a set of commonly under-stood metrics across the field. Two sets of metrics areimportant: operating metrics to measure internal per-formance (R&D and value added of PD PPP model);and output metrics to quantify potential public healthimpacts.

Operating measures could go beyond funds raisedand disbursed, and typical R&D metrics to highlightthe progress made by PD PPPs on value-added activi-ties. Some of the additional categories could include:2

• Building unique capabilities and platforms toattract and select the most promising projects.

• Improving their partners’ research capabilities.• Mobilizing funds in line with portfolio and or-

ganizational developments.• Enhancing knowledge and knowledge dissemi-

nation among research partners and the broaderpublic health actors involved in turning new prod-ucts into health impact.

• Progress towards the target (e.g., relative to aroad map).

Clear metrics for the field could benefit the PD PPPsin communicating their performance beyond the cur-rent audience. In addition, the cost of assessment andmonitoring for both donors and PD PPPs will becomesubstantial without common metrics. For funders in

particular, there is a strong desire to have output metricsfor the field that allow them to compare investment inPD PPPs with other types of investment. Well-definedand widely utilized metrics will not only serve thefunders but if action is taken based upon them, thiswill help to focus PD PPPs and reinforce the manage-ment rigour associated with the model.

Open questions■ What operational metrics are applied by PD PPPs

today? For whom? What works?■ What are the best practices from private industry?

Could PD PPPs use them?■ How can the value added of PD PPPs be measured

or tracked?■ Is there a way to quantify both social demand and

scientific maturity to enable comparison across thisfield and other public health investments?

Role of coordinationPD PPPs and the organizations funding them nowconstitute an increasingly large group. There appearto be potential opportunities for increased coordina-tion either amongst the funders or the PD PPPs

During the workshop many of the participants ex-pressed the view that coordination would be essentialfor broadening the funding base for the field. Whetherit is the funders or the PD PPPs, working together todevelop and deliver a simple set of messages about thePD PPP field will be more effective than a multitudeof individual efforts, which may be perceived as com-peting with one another.

An area that was of particular interest to the PDPPPs was a coordinated effort to address some of thesystemwide issues that all PD PPPs now face or willface, but which are too large for an individual PD PPPto tackle alone. Some issues were highlighted, such asregulatory harmonization and simplification, clinicaltrial and ethical review capacity and investment in de-livery infrastructure in disease-endemic countries.


1 Global Alliance for Vaccines and Immunization 2002. Accel-erated introduction of new priority vaccines in developing coun-tries. Prepared for GAVI, the World Bank, and the Bill &Melinda Gates Foundation by McKinsey & Company. 76 pp.

2 See annex 9e (Pfitzer M. Demonstrating value: Performancemetrics for health product development public-private partner-ships).

However, additional areas would most probably ben-efit too.

The meeting also discussed the potential benefits ofinvestment in shared resources across the PD PPPs inareas such as data management, intellectual propertyand regulatory skills. Amongst the PD PPPs, a smallgroup of the better-established organizations are con-nected to varying degrees with information beingshared between executives and, increasingly, their staffmembers. PD PPPs themselves will need to drive anyfurther coordination or even collaboration amongstthem. In general, there were some reservations abouthow much coordination on core operational activitieswould be beneficial. There was some concern from thePD PPPs that additional umbrellas organizations couldcreate additional burdens to getting their work done.

Open questions■ How can donors work together to help address some

of the systemic challenges facing the field (e.g., regu-latory harmonization, public health policies, etc.)?

■ What are the best ways for the field to coordinatework on advocacy for the model?

■ Should funders coordinate to reduce transactioncosts for PPPs and themselves (e.g., independentassessment of PD PPPs, common frameworks forproposals, etc)?

■ Would investment in shared resources for the PDPPPs be beneficial or desirable?

■ Is there value to having a body that represents thePD PPPs collectively?

Meeting takeaways■ PD PPPs are at present the best approach to devel-

opment of products to combat diseases of poverty.■ Product development (customer needs and techni-

cal development) should remain the core focus ofthe PD PPPs; other roles will be determined by thecontext in which they operate.

■ Both similarities and differences across PD PPPsneeds to be recognized.

■ Increased involvement of the disease-endemic coun-tries along the R–D–A continuum is critical to long-term, sustainable product development and adoptionof successful products.

■ Currently a funding gap for product developmentin neglected diseases exists; exact funding needs arestill not fully known.

■ Development of some common operating perform-ance metrics and measures of likely public healthimpact would be beneficial to PD PPPs and funders.

■ Additional sources and mechanisms for fundingproduct development will need to be mobilized;both ‘push’ and ‘pull’ mechanisms will be required.

■ Mobilizing new sources of funding will require acoordinated effort by current funders and PD PPPs.


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Areas for future attentionRoy Widdus and Katherine White

Development of common performance measuresThe need for the development and implementation ofsome commonly recognized, comparable measures bywhich to assess the performance and progress of thePD PPPs was highlighted at the workshop itself, at thedonor consultation associated with the workshop andby many of those involved in the post-workshop con-sultation.

Recognizing that each of the PD PPPs has a differ-ent set of objectives and that these will evolve overtime, there was still strong feeling that the benefits ofrecognized quantitative and qualitative measures ofperformance would be significant for the PD PPPsthemselves, current and future funders of PD PPPs, aswell as their potential partners.

Desirable performance measures mentioned duringthe meeting included:

• Estimates of the potential public health impactand cost-utility of new products

• Quantitative productivity goals• Measures of PD PPP ‘added value’ including the

effectiveness of their portfolio management ap-proaches for public health outcomes.

Those funding PD PPPs today and in the future willalways have their own strategies and preferences forareas of investment (e.g., specific diseases, specific stagesof development, etc.). However, they all need to beable to evaluate the performance of their investments.A common set of measures will help ensure an objec-tive evaluation of how well an organization is perform-ing against specific goals and relative to other similartypes of organization. Likewise for PD PPPs, the op-portunity to develop a track record may also facilitatelonger-term financial commitments from funders asinvestments are made based not just on achievement

A R E A S F O R F U T U R E A T T E N T I O N

As the global commitment to address the burden ofcommunicable diseases associated with poverty in-

creases, so too does the awareness of the need for newtreatments and interventions to address these diseases.To date, the PD PPPs have shown themselves to bethe most promising vehicle by which to develop thesemuch-needed tools. The momentum that has devel-oped behind the current array of PD PPPs in the pastfive years is impressive, but there is more to be done ifthey are to achieve their full potential and provide thebest return on investment.

During the IPPPH workshop in April 2004 anumber of areas requiring further attention was iden-tified. Addressing these areas will help ensure the con-tinued progress of the PD PPPs. While the participantscame to no specific consensus conclusions about therelative priority of these activities during the workshop,its organizers have solicited further input from theoverall meeting co-chairs, the session co-chairs, cur-rent funders of the PD PPPs, the PD PPP CEOs andparticipants from African countries to develop someconsensus about the priority areas to be addressed.

The following section represents a synthesis of theinput from these groups combined with the discus-sions during the workshop.

Addressing the following challenges will most likelyenhance the probability for ultimate success of the PDPPPs:

• Development of common performance measures.• Coordination on clinical trial capacity develop-

ment.• Harnessing the potential of the disease endemic

countries.• Ensuring financial sustainability of the PD PPPs.• Communication and coordination.• Fully recruiting potential industry contributions.

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of milestones but also improvements in performance.The availability of public information and the devel-opment of a performance track record will also helpindustry partners, researchers and other stakeholders.Strong indicators will provide valuable data with whichthey can make the case for getting involved with aspecific PD PPP.

Estimates of potential public health impact of newproducts start within the burden of the disease tar-geted. However, they also take into account the prob-ability of success in product development per se, thetime to success and the subsequent time to wide appli-cation. They need to incorporate some estimate of thefraction of the theoretical target population that wouldactually be reached given the likely delivery systems,and the efficacy of the intervention. Combined withthe costs of product development and the costs ofapplication, such cost-utility measures would provideinvestors additional information to help inform deci-sions. Admittedly, such estimates incorporate projectionsthat are often uncertain but the effects of these on therobustness of conclusions can be determined by sensi-tivity analyses using a range of plausible predictions.

Such analyses of potential public health impact havebeen used by the National Institute of Allergy and In-fectious Diseases, for vaccines1,2 and could be easilyextended to other products.

Productivity goals do not necessarily need to incor-porate or assume guarantees of success in deliveringnew products. Where there is higher lack of certaintyabout scientific success (e.g., some ‘first-in-class’ vac-cine development efforts) productivity goals can beframed in terms of process measures (e.g., moving xcandidates from development stage b to developmentstage e). Quantitative productivity goals will enable PDPPPs the better to calculate and negotiate for the fund-ing they need to pursue their mission. Without a clearsense of what will be attempted, funding will be moredifficult to negotiate and evaluate.

Some meeting participants informally expressed res-ervations about the feasibility and use of common per-formance measures; they argued that the activities ofeach PD PPP were so different scientifically that nocommon measures could be found. Some were alsoapprehensive about the use of such measures for com-parison.

Marc Pfitzer3 discussed the ‘value’ that PD PPPs

provide for funders. This value actually lies at levelsother than the strictly scientific aspect of productdevelopment, where most of the variation between dif-ferent disease/product targets actually occurs. Suchvalue is represented in the quality of the scientificadvice brought to bear on decisions, the quality ofproject oversight and coordination across multiple play-ers, in the rigorous execution of project managementapproaches and in cost controls. PD PPPs need to con-sider their value-added contributions. If PD PPPs them-selves define the way in which their approach adds value,they will be contributing to the creation of commonperformance measures.

This may require extensive consultation to achieveagreement on meaningful approaches, but eventuallyshould help the ventures as well as their funders.

Related to added value is the relatively unquantifiedarea of portfolio management approaches for publichealth goals. As pointed out by Towse and colleagues,4

data and techniques for commercial portfolio manage-ment are mostly based on drug candidate attrition rates.Further work specifically for vaccine candidates wouldbenefit a range of PD PPPs addressing vaccines.

PD PPPs apprehensive about use of common per-formance measures should recognize that comparisonsare already being made now by measures that are notidentified explicitly. They will be better able to maketheir case if funders are using specific criteria for com-parisons.

Successful establishment and development of suchmetrics will take time and require the buy-in and longterm commitment of both the PD PPPs and theircurrent funders. The challenge for funders (and possi-bly management consultants or other impartial actors)is to define common performance measures that canbe used legitimately across different PD PPPs. Carewill also need to be taken to ensure that common per-formance measures are used appropriately, and thatlegitimate reasons for differences, e.g., differences in

1 Institute of Medicine, 1986. New Vaccine Development: Estab-lishing Priorities. Volume 1: Diseases of Importance in the USA.458 pp.; Volume 2: Diseases of Importance in DevelopingCountries. 432 pp. National Academies Press, Washington, DC.

2 Institute of Medicine, 1999. Vaccines for the 21st Century: Atool for decision making. 476 pp. National Academies Press,Washington, DC.

3 See annex 9e (op. cit.).4 See annex 9a (op. cit.).

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the level of scientific challenge resulting from disease/product choice, are taken into account.

Coordination on clinical trial capacity developmentAs many of the PD PPPs make progress and bringcandidates successfully into the later stages of devel-opment, the need for clinical trial capacity in DECshas become increasingly urgent. Phase III clinical trials are one of the most critical and expensive stagesof the development process (Di Massi et al. estimates30 per cent of successful drug products’ developmentcosts are incurred during phase III trials1), and this isprobably higher for vaccines.

Today, despite the many groups working to developclinical trial sites and the predicted demand for suchsites, there is still insufficient capacity and overall ca-pability in disease-endemic countries to meet existingdemand. This shortage of capacity will lead to unduecompetition for sites and costly delays to the clinicaldevelopment of these much-needed products unless itis addressed.

Increased coordination among funding agencies andproduct developers for ‘neglected diseases’ will helpensure funds are invested efficiently and in such a wayas to ensure the capacity can be sustained. Such coor-dination may involve groups working together acrossmultiple dimensions including the development oftraining programmes, sequencing and timing of trials,development of sites and/or establishment of multi-trial sites. From discussions with the African partici-pants they may be well placed to take the lead incoordinating across the PD PPPs (see discussion below).

If, wherever possible, PD PPPs adopted commontrials data management systems, then training, trialsimplementation and analysis would be facilitated.

Without close collaboration between the agenciescurrently developing sites, the PD PPPs and resourcesin the disease-endemic countries, it is highly unlikelythat the urgently needed trial capacity will be availablein time.

Harnessing the potential of disease-endemiccountriesDuring the meeting and in follow-up discussions, therewas strong agreement about the importance of legiti-mate involvement of the various constituents from thedisease-endemic countries. While there are many ex-


amples within PD PPPs of DEC scientists and institu-tions playing critical roles, there still are additional op-portunities for increased involvement and needs in thesecountries, e.g., regulatory capacity strengthening re-lated to rapid uptake. Some opportunities may be im-mediate, but leveraging the full potential that the DECshave to offer will require investment in new capacity.The African participants highlighted three areas ofopportunity (and these are likely to be explored fur-ther by them in a workshop scheduled for August2004).

Clinical trial capacity developmentWhile no specific resources are available in Africa to-day to assist with the general development of clinicaltrial sites, many of the activities required to providesuch service could, with some targeted training andsystem development, be handled by personnel trainedand living in Africa.

R&D on products from traditional African medicines (TAM)Throughout Africa there is widespread use of tradi-tional medicinal plants as health measures by traditionalhealth practitioners.2 While not developed underrecognized regulatory processes, the numerous plantspecies with potential medicinal used in TAMs couldbe a valuable source of product ideas and leads. Net-working institutions in the field and linking to phar-maceutical development expertise would be useful.

African Scientific and Technical Review CommitteeToday product developers make trial applicationsthrough bodies in Europe and the United States. As aresult IRB members are trained in line with Europeanand US ethics and standards. While these standardsare important, so too are experience and credibilitywith the African communities. Within Africa there arecurrently enough individuals with sufficient experienceof both cultures to enable the establishment of anAfrican Scientific and Technical Review Committeewhich could help improve the smooth running of tri-

1 Di Massi JA, Hansen RW, Grabowski HG. The price of inno-vation: new estimates of drug development costs. Journal ofHealth Economics, 22(2003) 151–185.

2 See annex 11 (Kimanani E, Akanmori B, Gamaniel K, InyangU, Kilama J, Kitua A, Leke R, Pallangyo K. Consolidation ofthe Private Partnership For Product Development: Africa’s Role).


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Enhanced communication and coordination are neededboth across different product development efforts andalso along the R–D–A continuum.

While additional coordination should improve over-all efficiency and prospects for success, it should beseen as a means to an end, not a goal in its own right.Proposed information exchange and coordinationactivities should be considered carefully so as not toimpose unnecessary burdens on already busy individu-als and ventures.

PD PPPs should consider where there is advantagein:

• Information sharing, e.g., on deal making and/or intellectual property management.

• Coordinated action, e.g., possibly on commonsystems for clinical trials data management.

• Collective advocacy, e.g., for attention to prod-uct development to achieve the MillenniumDevelopment Goals.

• Collective action for resolution of common prob-lems, e.g., strengthening of regulatory capacityin disease endemic countries.

• Development of methods (especially for vaccines)of portfolio management based on likely publichealth benefits.

Funders should continue dialogue on:

• Their desire for common performance metrics• Opportunities to coordinate funding• Strategies to expand the pool of funding.

Players along the R–D–A continuum for particulardiseases should consider what communications andcoordination vehicles would be useful:

• To ensure that necessary information for policydecisions (e.g., on public health utility) is devel-oped in a timely fashion (not sequentially/sub-sequently to product development itself)

• To best ensure anticipatory action (e.g., estimat-ing demand, ensuring financing and strengthen-ing delivery systems for rapid uptake) is plannedand undertaken in a timely fashion.

One facet of coordination along the R–D–A continuumthat particularly deserves additional attention is thetranslation of concepts relevant to combating‘neglected diseases’ from basic research to the statusof candidate products. This ‘translational research’ is

als in Africa. The ‘critical mass’ available at a regionallevel could help train and develop capacity includingthat for regulatory approval in the individual majorcountries of the region.

If the full potential of the DECs is brought to bearon the challenges faced by the PD PPPs, there is amuch higher likelihood that these countries will feeltruly involved. They will thus take greater ownershipof the end products that are developed and will con-tribute both in-kind and financially to their develop-ment and rapid utilization.

Ensuring financial sustainability of the PD PPPsDespite significant success in raising and mobilizingfunds the PD PPPs are still under-resourced. Whilethe exact size and timing of future funding requiredby the PD PPPs is difficult to ascertain precisely, therewas strong agreement about the severity of the fund-ing gap and concerns that the current base of fundersis not sufficient to sustain the existing field.

Maintaining the current level of funding and attract-ing additional support beyond the traditional ‘devel-opment’ funders will require better understanding ofthe size and timing of the current funding gap and aclear case for the benefits of investment in productdevelopment and the PD PPPs. For some of the smallergovernments and potential funders, finding an efficientway to get them involved will also be critical as they donot have the capacity to individually assess all PD PPPinvestment opportunities.

Both the industry executives and current funders ofthe PD PPPs will need to work together if they are todevelop effectively and deliver clearly the requiredmessages about the potential value of investing in thePD PPPs.

Communication and coordination amongplayers in the research–development–access(R–D–A) continuumIt became apparent during the IPPPH’s London work-shop that some level of contact among different play-ers in the R–D–A continuum exists, e.g., occasionalcontacts between PD PPPs. However, it is unrealisticto believe that the current level of communication andcoordination is optimal. Indeed, the meeting was thefirst time that the PD PPP ‘executives’ and their majorfunders had met to share information and viewpoints.

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of concern to both basic research funders who want tosee results in terms of health benefits, not only scien-tific knowledge, and to PD PPPs who need to be as-sured of an adequate flow of scientifically validcandidate products into their portfolios.

Although not cited by any PD PPP as their majorcurrent obstacle, it is a persistent concern, particularlyfor fields that have been relatively more neglected (e.g.,tuberculosis and uniquely tropical diseases likeTrypanosomiasis). Hence it deserves attention now toenhance the prospects of return on basic research in-vestment and long-term PD PPPP success. A study ofcurrent efforts in translational research and workshopsto enhance coordination between basic research andPD PPPs (or some other means to achieve this goal) iswarranted.

Fully recruiting potential industry contributionMany participants in the IPPPH’s London meetingexpressed the view that – overall – the experience and

expertise of pharmaceutical companies, particularly thelarger ones, could and should be more fully recruitedto the ‘enterprise’ of product development for diseasesassociated with poverty. Contributions from industrycould assist at various levels: the individual project level;overall portfolio PD PPP management; and in funders’assessments of individual PPP functioning.

Decisions about different sorts of engagement willbe taken at the individual company level, and often ona case-by-case basis in response to specific requests.Therefore, it is difficult to devise a general strategy forenhancing the engagement of pharmaceutical compa-nies with PD PPPs and their funders. Suggestions aremade in the following section (Moving forward).

Notwithstanding the situation described above, thepotential for instituting exchange schemes betweenpublic/governmental sector, pharmaceutical compa-nies, and the not-for-profit sector should be exploredas a means of improving understanding and knowl-edge transfer.


Moving forwardRoy Widdus

Coordination among PD PPPsAs of publication, the Initiative on Public-Private Part-nerships for Health and its parent organization, theGlobal Forum for Health Research, are assessing itsfuture role. Information on coordination among PDPPPs will be posted on the IPPPH website and canalso be obtained from the major PD PPPs.

For further information, visit the IPPPH website oremail the Secretariat at [email protected].

Coordination among disease-endemic countryresearchers and policy-makers regarding capacitystrengtheningSubsequent to the London workshop, African partici-pants convened a workshop on 30 August to 1 Septem-ber 2004 in Nairobi, Kenya to discuss theircontributions to product development for diseases en-demic in sub-Saharan Africa. It is planned to post thereport of the meeting on the IPPPH and TDR websiteswith contact details for sources of further information.A plan for activities under the umbrella of the AfricanHealth Research Forum is under development.

Coordination along the research-development-access continuumCoordination among players and funders along theR–D–A continuum is probably organized most easilyon a disease-oriented basis. Hence, the IPPPH Secre-tariat will be exploring with other parties the level ofinterest in periodic meetings of relevant players. IPPPHwill, therefore, consult with the general coordinationsecretariats for various diseases, including those for theStop TB Partnership, the Roll Back Malaria Partner-ship and the HIV/AIDS and Communicable DiseasesDepartments of the World Health Organization. For

M O V I N G F O R W A R D

The workshop convened by IPPPH in April 2004 rep-resents the first time representatives of all major not-

for-profit ventures for ‘neglected disease’ productdevelopment and their principal funders had everassembled to discuss issues of common interest inaddressing diseases associated with poverty.

While the field is diverse, the Meeting summary andthe emerging themes in Areas for future attentionidentified a range of issues where further discussionamong various players will enhance the prospects forsuccess. The best mechanisms for facilitating these fur-ther discussions are also in the process of definition.

Donor coordinationThe principal PD PPP funders which had participatedin planning the workshop (the Bill & Melinda GatesFoundation, the UK Department for InternationalDevelopment, the Rockefeller Foundation and theWellcome Trust) convened after the workshop a smallconsultation among current PD PPP funders to dis-cuss issues of shared concern. Conclusions of that meet-ing are provided in the Annexes in the full meetingreport.1

As of the time of publication, this Donor Consulta-tion Group is working to define an agenda of work toaddress their concerns.

To contact the group, write to Dr Charles Gardner,Associate Director, Health Equity, The RockefellerFoundation, at <[email protected]> or KatherineWhite at <[email protected]>.

1 See annex 10 (Donor Consultation on Policy and Programmingfor PD PPPs, 16 April 2004, The Wellcome Trust, London, UK).

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further information, see the IPPPH website or con-tact the Secretariat via <[email protected]>.

Recruiting potential industry contributionsAs noted above, pharmaceutical companies will mostprobably make decisions on engagement in differentaspects of developing products for disease associatedwith poverty at individual company level, or even acase-by-case basis, as their in-house R&D activities andpolicies/philosophies vary.

Given this situation, proposing an overall monolithicapproach to more fully recruiting industry expertisemay not be as useful as pursuing their fuller involve-ment in the various forums noted above, particularlythe proposed disease-specific discussions that will bringtogether different players along the research-develop-ment-access continuum.

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Post-workshop consultationon Meeting summary and Areas for future attention


All PD PPPs were given the opportunity to respond to drafts of the Meeting summary and Areas for futureattention before their finalization. Significant contributions to or comments on the Meeting summary and/or

Areas for future attention were received from the following meeting participants:

Patricia Danzon, The Wharton School, University of Pennsylvania, USA (Session Co-chair)

Charles Gardner, The Rockefeller Foundation, USA (Co-organizer)

Michael Harper, Consortium for Industrial Collaboration in Contraceptive Research/ContraceptiveResearch and Development Program (CICCR/CONRAD)

Jane Haycock, Department for International Development, United Kingdom (Co-organizer)

Hannah E. Kettler, Bill & Melinda Gates Foundation, USA (Co-organizer)

Ebi Kimanani, International Biomedical Research in Africa (IBRIA), Kenya [On behalf of the African meetingparticipants, namely: Rose Leke (Cameroon), Bartholomew Akanmori (Ghana), Uford Inyang (Nigeria),Andrew Kitua (Tanzania), Kisali Pallangyo (Tanzania), and John Kilama (Uganda)]

Andrew Y. Kitua, National Institute for Medical Research (NIMR), Tanzania

Adel Mahmoud, Merck Vaccines, USA (Meeting Co-chair)

Sigrun Møgedal, NORAD, Norway (Meeting Co-chair)

Melinda Moree, Malaria Vaccine Initiative, USA

Gwynne Oosterbaan, Global Alliance for Tuberculosis Drug Development (TB Alliance), USA

Sue Perl, Consultant to The Rockefeller Foundation, United Kingdom (Co-organizer)

Adrian Towse, Office of Health Economics, UK

Annexes

ANNEX 1

AgendaWorkshop on ‘Combating Diseases Associated with Poverty: Financing Strategies for

Product Development and the Potential Role of Public-Private Partnerships’15–16 April 2004

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A N N E X 1 . A G E N D A

DAY ONE THURSDAY 15 APRIL 2004

8.30 am–9.00 am Registration for badges (Reception Hall)SESSION I Purpose: To introduce the issues to be addressed in the workshop and particularly, in the keynote address, to identify the

expertise that is essential for product development, to identify who possesses these skills, and to provide an overview ofhow product development (PD) public-private partnerships (PPPs) recruit these in the interests of global public health.

9.00 am–9.10 am Welcome■ Mark J. Walport, Director, Wellcome TrustIntroduction of Meeting Co–chairs:■ Adel Mahmoud, Merck Vaccines (Merck & Co., Inc.), USA■ Sigrun Møgedal, Norad, Norway

9.10 am–9.20 am Aims of the workshop■ Roy Widdus, Initiative on Public-Private Partnerships for Health, Geneva, Switzerland

9.20 am–9.30 am Overview of programme■ Co-chairs

9.30 am–10.30 am Linking private sector expertise in product development with public sector goals to combat global healthproblems■ Gail H. Cassell, Ph.D., Eli Lilly and Co., USAQuestions and discussion

10.30 AM–11.00 AM COFFEE/TEA BREAK (FRANKS ROOM)

SESSION II Purpose: The session will clarify the benefits of pursuing a portfolio of candidate products, why it is appropriate to devel-opment of products to combat ‘neglected’ diseases, how the various not-for-profit PD ventures differ in scope and ap-proach, and how it is possible to measure their added value.

11.00 am–12.30 pm Chair:■ Gill Samuels, Pfizer Global Research and Development, UKPanel: Portfolio management in pharmaceutical companies and PD PPPs – based on background papers, withauthors on the panel responding to questions and with general discussion.■ Portfolio management in the pharmaceutical industry■ The emerging landscape of pubic-private partnerships for product development■ Demonstrating value: Performance metrics for health product development public-private partnershipsQuestions and discussion

12.30 PM–1.30 PM LUNCH (FRANKS ROOM)

SESSION III Purpose: To examine the specific role of PD PPPs and that of other necessary other players in the chain from ‘upstream’basic research through clinical trials to ‘downstream’ uptake and widespread product use.

1.30 pm–3.30 pm Co-chairs:■ John La Montagne, National Institutes of Health, USA■ Andrew Kitua, National Institute for Medical Research, Tanzania


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Panel: The role of PD PPPs and the environment necessary for their success – based on background papers, withauthors on the panel responding to questions and with general discussion.■ The emerging landscape of public-private partnerships for product development■ The current research-to-development ‘hand-off’ process for product concepts/candidate products and possible im-provements in it■ Ethical review capacity: Country needs, role and responsibility of partners and researchers■ Current status of clinical trials capacity in Africa■ Emerging lessons in preparing for uptake of new vaccinesQuestions and discussion

3.30 PM–4.00 PM COFFEE/TEA BREAK (FRANKS ROOM)

SESSION IV Purpose: To examine the funding needed for product development, the needs of PD PPPs themselves, plus the possiblealternatives to such ventures and their costs

4.00 pm–6.00 pm Chair:■ Patricia Danzon, University of Pennsylvania, USAWhat is the current financial situation for PD PPPs using the portfolio management approach? – based on abackground paper.■ Adrian Towse, Office of Health Economics, UKPanel: Financial aspects of product development for neglected diseases – based on above presentation andbackground papers, with authors on the panel responding to questions and with general discussion.■ Revising current predictions of PD PPP needs■ Requirements for vaccine product and field site development at a licensure standard■ What are the alternative approaches for ‘neglected’ product development and their costs?Questions and discussionEND OF DAY ONE

6.30 PM–RECEPTION-DINNER

The Wellcome Trust■ Guest Speaker: Gordon Conway, President, The Rockefeller Foundation

DAY TWO FRIDAY 16 APRIL 2004

8.45 am–9.00 am Summary of conclusions from Day OneCo-chairs

SESSION V Purpose: To assess the possibilities for financing for product development from non-traditional sources9.00 am–10.30 am Chair:

■ Jane Haycock, DFID, United KingdomPossible innovative approaches to funding product development for neglected health problems? – basedon above presentation and background papers, with authors on the panel responding to questions and with generaldiscussion.■ Innovative financing approaches for ‘neglected’ product development■ The possibility of tapping major financial flows to disease-endemic countries■ The need for a ‘business case’ approachQuestions and discussion

10.30 AM–11.00 AM COFFEE/TEA BREAK (FRANKS ROOM)

SESSION VI General discussion: What are the remaining questions?11.00 am–12.45 pm Meeting Co-chairs

■ Adel Mahmoud, Merck Vaccines (Merck & Co., Inc.), USA■ Sigrun Møgedal, Norad, Norway

12.45 pm–1.00 pm Discussion for all participants1.00 pm Establishment of Follow-up Monitoring Group

CLOSURE

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A N N E X 2 . L I S T O F P A R T I C I P A N T S

ANNEX 2

List of participants

Bartholomew Dicky Akanmori, Associate Professor andHead of Department, Noguchi Memorial Institute forMedical Research (NMIMR), University of Ghana, BoxLG 581, Legon, Accra, Ghana (Also: Chair, EuropeanDeveloping Countries Clinical Trials Partnership)Tel.: 233 21 501178/501179; fax: 233 21 502182;e-mail: [email protected]

Garry Aslanyan, Senior Health Advisor, Canadian Interna-tional Development Agency (CIDA), 200 Promenadedu Portage, Gatineau, Québec, CanadaTel.: 1 819 997 4871; fax: 1 819 934 0632;e-mail: [email protected]

Martin Bates, Project Leader, Diseases of the DevelopingWorld, GlaxoSmithKline, 980 Great West Road,Brentford, Middlesex TW8 9GS, UKTel.: 44 208 047 4744; fax: 44 208 047 0670;e-mail: [email protected]

Amie Batson, Senior Health Specialist, World Bank, MSNG7-701, 1818 H Street, NW, Washington DC, 20433,USATel.: 1 202 458 8300; fax: 1 202 522 3489;e-mail: [email protected]

Seth Berkley, President and Chief Executive Officer,International AIDS Vaccine Initiative, 110 WilliamStreet, 27th Floor, New York, NY 10038, USATel.: 1 212 847 1100/1102; fax: 1 212 847 1102;e-mail: [email protected] – [email protected]

Ted Bianco, Director of Technology Transfer, WellcomeTrust, 210 Euston Road, London NW1 2BE, UKTel.: 44 207 611 7300; fax: 44 207 611 8857;e-mail: [email protected] –[email protected]

Ian C. Boulton, Director, Global Commercial Strategy –Diseases of the Developing World, GlaxoSmithKline,980 Great West Road, Brentford, Middlesex TW8 9GS,UKTel.: 44 118 940 4711; fax: 44 118 940 0670;e-mail: [email protected]

Assia Brandrup-Lukanow, Director, Division of Health,Education, Social Protection, Deutsche Gesellschaft fürTechnische Zusammenarbeit (GTZ) Gmbh, Postfach5180, Dag-Hammarskjold-Weg 1-5, 65726 Eschbom,GermanyTel.: 49 61 96 79 80 1272; fax: 49 61 96 79 1366;e-mail: [email protected]

Ian Broadwater, Policy Analyst, Office of DevelopmentStudies, United Nations Development Programme(UNDP), 336 E. 45th St., Uganda House, 4th Floor,New York, NY 10017, USATel.: 1 212 906 3689; fax: 1 212 906 5657;e-mail: [email protected]

Ruairi Brugha, Consultant, Development CooperationIreland, London School of Hygiene and TropicalMedicine, Keppel Street, London WC1E 7HT, UKTel.: 44 207 927 2072; fax: 44 207 637 5391;e-mail: [email protected]

David Carr, Policy Officer, Wellcome Trust, 210 EustonRoad, London NW1 2BE, UKTel.: 44 207 611 8220; fax: 44 207 611 8742;e-mail: [email protected]

Dennis Carroll, Senior Infectious Diseases Advisor, USAgency for International Development (USAID),Bureau for Global Health, 1300 Pennsylvania Avenue,Washington DC 20523, USATel.: 1 202 712 5009; fax: 1 202 216 3702;e-mail: [email protected]

Gail Cassell, Vice President, Scientific Affairs and Distin-guished Lilly Research Scholar for Infectious Diseases,Eli Lilly and Company, Lilly Corporate Center, DC1050, Indianapolis, IN 46285, USATel.: 1 317 277 7374/277 8416; fax; 1 317 433 0066;e-mail: [email protected]

Herb Clemens, Chief Financial Officer, Foundation forInnovative Diagnostics (FIND), 71 Avenue LouisCasai, PO Box 93, 1216 Cointrin/Geneva, SwitzerlandTel.: 41 22 710 05 93/90; fax: 41 22 710 05 99; e-mail: [email protected]


5 0

Charles Clift, Secretary, Commission on IntellectualProperty Rights, Innovation and Public Health, WorldHealth Organization (WHO), 20 Avenue Appia, 1211Geneva 27, SwitzerlandTel.: 41 22 791 3168; fax: 41 22 791 4852;e-mail: [email protected]

Gordon Conway, President, Rockefeller Foundation, 420Fifth Avenue, New York, NY 10018, USATel.: 1 212 852 8400; fax: 1 212 852 8277;e-mail: [email protected] –[email protected]

Gillian Margaret Morrow Corken, CPO Country HeadBrazil, Quintiles Brasil Ltda, Av Francisco Matarazzon° 1400 – 13° Andar, Ed Milano, BrazilTel.: 55 11 3868 0568; fax: 55 11 3868 0580;e-mail: [email protected]

Susan Corning, Director, Global Health Philanthropy andInvestment Forum (GHPIF), Ivy Wood, WestropGreen, Cold Ash, Newbury, Berkshire RG18 9NW, UKTel.: 44 163 520 2886; fax: 44 870 125 3809;e-mail: [email protected]

Patricia Danzon, Celia MOH Professor, WhartonHealthcare Systems Department, 3641 Locust Walk,Colonial Penn Center, Room 207, Philadelphia, PA19104, USATel.: 1 215 898 5722; fax: 1 215 573 7025;e-mail: [email protected](Session chair)

Catherine Davies, Scientific Programme Manager,Wellcome Trust, 210 Euston Road, London NW1 2BE,UKTel.: 44 207 611 8692; fax: 44 207 611 7288;e-mail: [email protected]

Léna Edelman, Institut Pasteur, 28 rue Docteur Roux,75015 Paris, FranceTel.: 33 1 45 68 82 11; fax: 33 1 53 69 01 98;e-mail: [email protected]

Daniel T. Eksteen, Business Manager, Medical ResearchCouncil, Francie Van Zijl Drive, Parowvallei, CapeTown, 7505 Tygerberg, South AfricaTel.: 27 21 938 0551; fax: 27 21 938 0823;e-mail: [email protected]

Christopher Elias, President, Program for AppropriateTechnology in Health (PATH), 1455 NW Leary Way,Seattle, WA 98107-5136, USATel.: 1 206 788 2492; fax: 1 206 788 2007;e-mail: [email protected]

Justine Frain, Vice President, GlaxoSmithKline, 980 GreatWest Road, Brentford TW8 9GS, UKTel.: 44 208 047 5519; fax: 44 208 047 0684;e-mail: [email protected]

Maria Freire, Chief Executive Officer, Global Alliance forTB Drug Development, 80 Broad Street, 31st Floor,New York, NY 10004, USATel.: 1 212 227 7540 (ext. 222); fax: 1 212 227 7540;e-mail: [email protected]

Charles A. Gardner, Associate Director, Health Equity,Rockefeller Foundation, 420 Fifth Avenue, New York,NY 10018-2702, USATel.: 1 212 852 8313; fax: 1 212 852 8279;e-mail: [email protected]

Cathy Garner, Chief Executive Officer, Centre for theManagement of IP in Health R&D (MIHR), OxfordCentre for Innovation, Mill Street, Oxford OX2 0JX,UKTel.: 44 186 581 2041; fax: 44 186 572 6965;e-mail: [email protected]

Kim Gauvin, External Relations Officer, WHO, 20 AvenueAppia, 1211 Geneva 27, SwitzerlandTel.: 41 22 791 4919; e-mail: [email protected]

Gargee Ghosh, Program Manager, Global Health PolicyResearch Network, Center for Global Development,1776 Massachusetts Avenue, NW, #301, WashingtonDC 20036, USATel.: 1 202 416 0741; fax: 1 202 416 0755;e-mail: [email protected]

Chris Gingerich, Consultant to the Bill & Melinda GatesFoundation and the World Bank, Oakwood SymphonyPlace, 1117 Marquette Avenue Apt # 1709,Minneapolis, MN 55403, USATel.: 1 310 339 1432; fax: 1 815 550 9516;e-mail: [email protected]

Scott B. Halstead, Interim Director, Pediatric DengueVaccine Initiative, 5824 Edson Lane, Rockville, MD20852, USATel.: 1 301 984 8704; fax: 1 301 984 4423;e-mail: [email protected]

Michael Harper, Professor and Director, Consortium forIndustrial Collaboration in Contraceptive Research(CICCR/CONRAD), Contraceptive Research andDevelopment Program (CONRAD), 1611 North KentStreet, Suite 806, Arlington, VA 22209, USATel.: 1 703 524 4744; fax: 1 703 524 4770;e-mail: [email protected]

Jane Haycock, Health Adviser, Department for Interna-tional Development (DFID), 1 Palace Street, LondonSW1E 5HE, UKTel.: 44 207 023 1610; fax: 44 207 023 0428;e-mail: [email protected](Session chair)

5 1


David Hayward, Head, Finance and Administration,Global Forum for Health Research, 20 Avenue Appia,1211 Geneva 27, SwitzerlandTel.: 41 22 791 1604; fax: 41 22 791 4394;e-mail: [email protected]

Chris Hentschel, Chief Executive Officer, Medicines forMalaria Venture (MMV), ICC Building, 20 Route dePré-Bois, 1215 Geneva 15, Switzerland

Tel.: 41 22 799 4060; fax: 41 22 799 4061;e-mail: [email protected] – [email protected]

Ahvie Herskowitz, Chief Operating Officer, Institute forOneWorld Health, 580 California Street, Suite 900,San Francisco, CA 94104, USATel.: 1 415 421 4700; fax: 1 415 421 4747;e-mail: [email protected]

Tharald Hetland, Senior Adviser, Department of PublicHealth, Ministry of Health, PO Box 8011 Dep, 0030Oslo, NorwayTel.: 47 22 24 86 42; fax: 47 22 24 86 56;e-mail: [email protected]

Arnd Hoeveler, Head of Unit “Combating the majorcommunicable diseases linked to poverty”, EuropeanCommission – Research Director General, SDME 7/25, 1049 Brussels, BelgiumTel.: 32 2 295 68 01; e-mail: [email protected]

Eivind Hovden, Adviser, Research Council of Norway, POBox 2700 St. Hanshaugen, 0131 Oslo, NorwayTel.: 47 22 03 70 41; fax: 47 22 03 70 01;e-mail: [email protected]

Uford Samson Inyang, Director General/Chief ExecutiveOfficer, National Institute for Pharmaceutical Researchand Development, Idu Industrial Area, PMB 21 Garki,Abuja, NigeriaTel.: 234 9 670 5167/670 0834; fax: 234 9 523 1043;e-mail: [email protected]

Søren Jepsen, Executive Director, European MalariaVaccine Initiative, c/o Statens Serum Institut,Artillerivej 5, 2300 Copenhagen K, DenmarkTel.: 45 32 68 31 88; fax: 45 32 68 32 28;e-mail: [email protected]

Amina Jindani, Consultant, 2 Grande Serpentine, Parc desAigles, 60270 Gouvieux, FranceTel.: 33 3 44 57 02 19; e-mail: [email protected]

Trevor Jones, Director General, Association of the BritishPharmaceutical Industry, 12 Whitehall, London SW1A2DY, UKTel.: 44 207 747 1424; fax: 44 207 747 1416;e-mail: [email protected]

Hannah E. Kettler, Program Officer, Global HealthStrategies, Bill & Melinda Gates Foundation, PO Box23350, Seattle, WA 98102, USATel.: 1 206 709 3482; fax: 1 206 709 3170;e-mail: [email protected]

Gerald T. Keusch, Provost and Dean for Global Health,Boston University, 715 Albany Street, Boston, MA02118, USATel.: 1 617 638 4687; fax: 1 617 638 4476;e-mail: [email protected]

John Kilama, President, Global Bioscience DevelopmentInstitute, Inc. (GBDI), 702 West Street, Suite 205,Wilmington, DE 19801, USATel.: 1 302 656 6439; fax: 1 302 656 6442;e-mail: [email protected]

Ebi Kimanani, Principal Program Developer, InternationalBiomedical Research Institute, 25 Circle Beaconsfield,Quebec, H9W 5B6, CanadaTel.: 1 514 697 5902; fax: 1 514 697 6597;e-mail: [email protected]

Andrew Y. Kitua, Director General, National Institute forMedical Research (NIMR), Ocean Road, PO Box9653, Dar es Salaam, TanzaniaTel.: 255 22 213 1864/212 1376-9; fax: 255 22 2121380; e-mail: [email protected] – [email protected](Session co-chair)

John La Montagne, Deputy Director, National Institute ofAllergy and Infectious Disease, National Institutes ofHealth, 31 Center Drive, Bethesda, MD, USATel.: 1 301 496 9677; fax: 1 301 496 4409;e-mail: [email protected](Session co-chair)

Richard Laing, Medical Officer, WHO, 20 Avenue Appia,1211 Geneva 27, SwitzerlandTel.: 41 22 791 4533; fax: 41 22 791 4167;e-mail: [email protected]

Jacques Laruelle, Senior Programme Officer (PublicHealth), Directorate General for Development Coop-eration, Rue Brederod 6-1, 1000 Brussels, BelgiumTel.: 32 2 519 06 60; fax: 32 2 519 05 70;e-mail: [email protected]

Rose G.F. Leke, President, Board of Directors, Institute ofMedical Research and Studies of Medicinal Plants(IMPM), Cameroon, Faculty of Medicine and Biomedi-cal Sciences, University of Yaounde 1, Yaounde,CameroonTel.: 237 222 5955; fax: 237 223 7429;e-mail: [email protected] – [email protected]


5 2

Joerg F. Maas, Executive Director, German Foundationfor World Population (DSW), Goettinger Chausee 115,30459 Hannover, GermanyTel.: 49 511 943730; fax: 49 511 2345051;e-mail: [email protected]

Daniel Maeusezahl, Special Adviser for Health andDevelopment, Swiss Agency for Development andCooperation, Freiburgstrasse 130, 3003 Berne,SwitzerlandTel.: 41 31 322 36 23; fax: 41 31 323 17 64;e-mail: [email protected]

Bruce Mahin, Treasurer and Board Member, Drugs forNeglected Diseases Initiative (DNDi), 1 Place St.Gervais, 1201 Geneva, SwitzerlandTel.: 33 1 53 28 10 80/33 6 15 64 06 86;e-mail: [email protected]

Adel Mahmoud, President, Merck Vaccines (Merck & Co.,Inc.), One Merck Drive (WS3A-07), WhitehouseStation, NJ 08889, USATel.: 1 908 423 3235; fax: 1 908 735 1232;e-mail: [email protected](Meeting co-chair)

Stephen A. Matlin, Executive Director, Global Forum forHealth Research, 20 Avenue Appia, 1211 Geneva 27,SwitzerlandTel.: 41 22 791 3418; fax: 41 22 791 4394;e-mail: [email protected]

Marissa A. Miller, Senior Advisor for Public HealthEmergency Preparedness, US Department of Healthand Human Services, 200 Independence Ave., Room624D, NW, Washington DC 20201, USATel.: 1 202 690 6013; e-mail: [email protected]

Sigrun Møgedal, Senior Adviser, Norwegian Agency forDevelopment Cooperation (NORAD), Ruseløkkven26, PB 8034 Dep, 0030 Oslo, NorwayTel.: 47 95055112; fax: 47 22242031;e-mail: [email protected](Meeting co-chair)

Mary Moran, Director, R&D Policy Group, LondonSchool of Economics, LSE Health and Social CareDepartment, Cowdray House, Houghton St., LondonWC2A 2AE, UKTel.: 44 779 143 8783; e-mail: [email protected]

Melinda Moree, Director, Malaria Vaccine Initiative, 1455NW Leary Way, Seattle, WA, USATel.: 1 206 788 2346; fax: 1 206 285 6619;e-mail: [email protected]

Angeline Nanni, Director of Vaccine Finance and Supply,GAVI’s Pneumococcal ADIP, Johns Hopkins UniversityBloomberg School of Public Health, 615 N. WolfeStreet, Baltimore, MD 21205, USATel.: 1 443 287 0835; fax: 1 410 614 1419;e-mail: [email protected]

Ole F. Olesen, Scientific Officer, Poverty-related diseases,European Commission – Directorate-General forResearch, De Meeûs Square 8, 1050 Brussels, BelgiumTel.: 32 2 295 39 99; fax: 32 2 295 53 65;e-mail: [email protected]

John Wyn Owen, Secretary, Nuffield Trust, 59 NewCavendish Street, London W19 7LP, UKTel.: 44 207 631 8456; fax: 44 207 631 8451;e-mail: [email protected]

Ariel Pablos-Mendez, Acting Director, Health Equity,Rockefeller Foundation, 420 Fifth Avenue, New York,NY 10018-2702, USATel.: 1 212 852 8348; fax: 1 212 852 8279;e-mail: [email protected]

Kisali Pallangyo, Professor, Department of Medicine,Muhimbili University College of Health Sciences,University of Dar es Salaam, PO Box 65066, Dar esSalaam, TanzaniaTel.: 255 222 151596; e-mail: [email protected]

Sue Perl, Consultant, Rockefeller Foundation, 13 CrescentLane, London SW4 9PT, UKTel.: 44 207 622 9541; fax: 44 207 622 9541;e-mail: [email protected]

Marc W. Pfitzer, Managing Director, Foundation StrategyGroup, PO Box 5702, Blvd Georges Favon 6, 1204Geneva, SwitzerlandTel.: 41 22 807 2482; fax: 41 22 807 2401;e-mail: [email protected]

Peter Potter-Lesage, Chief Financial Officer, Medicines forMalaria Venture (MMV), ICC, 20 Route de Pré-Bois,PO Box 1826, 1215 Geneva 15, SwitzerlandTel.: 41 22 799 4068; fax: 41 22 799 4061;e-mail: [email protected]

Sohaila Rastan, Director of Science Funding, WellcomeTrust, 183 Euston Road, London NW1 2BE, UKTel.: 44 207 611 8569; fax: 44 207 611 8528; e-mail:[email protected]

Olwen Renowden, Economist, Office of Health Econom-ics, 12 Whitehall, London SW1A 2DY, UKTel.: 44 207 930 9203 (ext. 1482);e-mail: [email protected]

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Robert Ridley, Director, Special Programme for Researchand Training in Tropical Diseases (TDR), WHO, 20Avenue Appia, 1211 Geneva 27, SwitzerlandTel.: 41 22 791 3802/3906; fax: 41 22 791 4854;e-mail: [email protected]

Patricia Atkinson Roberts, Senior CommercializationOfficer, Program for Appropriate Technology in Health(PATH), 1455 NW Leary Way, Seattle, WA 98103,USATel.: 1 206 788 2345; fax: 1 206 285 6619;e-mail: [email protected]

Zeda F. Rosenberg, Chief Executive Officer, InternationalPartnership for Microbicides, 1010 Wayne Avenue,Suite 510, Silver Spring, MD 20910, USATel.: 1 301 608 2221; fax: 1 301 608 2241;e-mail: [email protected] –[email protected]

Jane Rowley, Consultant, International AIDS VaccineInitiative, 135 Gloucester Terrace, London W2 6DX,UKTel.: 44 207 706 1213; fax: 44 845 334 1735/207894 6520; e-mail: [email protected]

Jerald C. Sadoff, President and Chief Executive Officer,Aeras Global TB Vaccine Foundation, 7500 OldGeorgetown Road, Suite 800, Bethesda, MD 20814,USATel.: 1 301 547 2900; fax: 1 301 547 2901;e-mail: [email protected]

Gill Samuels, CBE, Executive Director, Science Policy andScientific Affairs, Europe, Pfizer Global Research andDevelopment, Sandwich Laboratories, Ramsgate Road,Sandwich, Kent CT13 9NJ, UKTel.: 44 130 464 8258; fax: 44 130 465 2144;e-mail: [email protected](Session chair)

Alison Sander, Consultant, 74 Buckingham Street,Cambridge, MA 02138, USATel.: 1 617 868 1582; e-mail: [email protected]

Esther Schmid, Research Strategist, Pfizer Global R&D,Ramsgate Road, Sandwich, Kent CT13 9NJ, UKTel.: 44 130 464 3855;e-mail: [email protected]

Nina R. Schwalbe, Director, Network Public HealthPrograms, Open Society Institute, 400 West 59thStreet, New York, NY, USATel.: 1 212 548 0324; fax: 1 212 548 4610;e-mail: [email protected]

Valerie Snewin, Policy Officer, Wellcome Trust, 210Euston Road, London NW1 2BE, UKTel.: 44 207 611 7311; fax: 44 207 611 8742;e-mail: [email protected]

Roberto Solari, Chief Executive Officer, MRC Technol-ogy, 20 Park Crescent, London W1B 1AL, UKTel.: 44 207 291 5301; fax: 44 207 323 1331;e-mail: [email protected]

Paul Spray, Head of Central Research Department,Department for International Development (DFID), 1Palace Street, London SW1E 5HE, UKTel.: 44 207 023 0361; fax: 44 207 023 0105;e-mail: [email protected]

Wendy Taylor, Executive Director, BIO Ventures forGlobal Health, 1225 Eye Street, NW, Suite 400,Washington DC, 20005, USATel.: 1 202 962 9216; fax: 1 202 962 9201;e-mail: [email protected]

Martyn ten Ham, Senior Advisor for International Affairs,Ministry of Health, Welfare and Sports, Parnassusplein5, The Hague, The NetherlandsTel.: 31 70 340 7970; fax: 31 70 340 7187;e-mail: [email protected]

Sandy Thomas, Director, Nuffield Council on Bioethics,28 Bedford Square, London WC1B 3JS, UKTel.: 44 207 681 9619; fax: 44 207 637 1712;e-mail: [email protected]

Adrian Towse, Director, Office of Health Economics, 12Whitehall, London SW1A 2DY, UKTel.: 44 207 747 1407; fax: 44 207 747 1419;e-mail: [email protected]

Tomris Türmen, Representative of the Director-General,World Health Organization, 20 Avenue Appia, 1211Geneva 27, SwitzerlandTel.: 41 22 791 2757; fax: 41 22 791 4852;e-mail: [email protected]

Katalijne van Diest, Programme Coordinator, EuropeanDeveloping Countries Clinical Trials Partnership(EDCTP), PO Box 93015, 2509 AA, The Hague, TheNetherlandsTel.: 31 70 344 0891; 31 70 344 0899;e-mail: [email protected]

Harry Van Schooten, Senior Health Advisor, Ministry ofForeign Affairs, The Hague, The NetherlandsTel.: 31 70 3484467; fax: 31 70 3485366;e-mail: [email protected]

Mark Walport, Director, Wellcome Trust, 183 EustonRoad, London NW1 2BE, UKTel.: 44 207 611 8422; fax: 44 207 611 8735;e-mail: [email protected]



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Jonathan Weber, Dean, St Mary’s Campus, JefferissProfessor for GU Medicine & Communicable Diseases,G70, Imperial College London, Norfolk Place, LondonW2 1PG, UKTel.: 44 207 594 3901; fax: 44 207 594 3643;e-mail: [email protected] –[email protected]

John Wecker, Director, Rotavirus Vaccine Program, 1455NW Leary Way, Seattle, WA 98107, USATel.: 1 206 285 3500 Ext. 2455; fax: 1 206 285 6619;e-mail: [email protected]

Katherine White, Independent Consultant, 13 AirlieGardens, London W8 7AL, UKTel.: 44 790 392 6467; fax: 44 207 221 1732;e-mail: [email protected]

Wendy Woods, Vice President and Director, The BostonConsulting Group, Inc., Exchange Place, 31st Floor,Boston, MA 02109, USATel.: 1 617 973 4323; fax: 1 617 973 1339;e-mail: [email protected]

Elizabeth Ziemba, President, SHARED, Inc., OneHarvard Street, Suite 303, Brookline, MA, USATel.: 1 617 429 2900; fax: 1 617 739 5929;e-mail: [email protected]

IPPPH SecretariatPamela Atiase, Administrative Assistant, IPPPH, Global

Forum for Health Research, International CenterCointrin (ICC), Block G, 3rd Floor, 20 Route de Pré-Bois, PO Box 1826, 1215 Geneva 15, SwitzerlandTel.: 41 22 799 4086; fax: 41 22 799 4089;e-mail: [email protected]

Karin Holm, Senior Programme Officer, IPPPH, GlobalForum for Health Research, International CenterCointrin (ICC), Block G, 3rd Floor, 20 Route de Pré-Bois, PO Box 1826, 1215 Geneva 15, SwitzerlandTel.: 41 22 799 4081; fax: 41 22 799 4089;e-mail: [email protected]

Roy Widdus, Project Manager, IPPPH, Global Forum forHealth Research, International Center Cointrin (ICC),Block G, 3rd Floor, 20 Route de Pré-Bois, PO Box1826, 1215 Geneva 15, SwitzerlandTel.: 41 22 799 4088/4086; fax: 41 22 799 4089;e-mail: [email protected]

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ANNEX 3A

Background on the product development public-privatepartnerships under consideration

the pharmaceutical industry. Many PD PPPs planningto utilize a portfolio approach are at an early stage ofdevelopment.

The strategic starting point for other PD PPPs is aparticular candidate product (or a very small numberof these). IPPPH refers to these partnerships as project-based PD PPPs.2 Portfolios are obviously built up ofindividual projects, but some projects are pursued in-dependently (see Appendix B).

The upcoming workshop concentrates on those PDPPPs strategically focused on a portfolio of candidateproducts.

NB. IPPPH recognizes that these distinctions aresomewhat subjective, but the multiple candidate/portfolio approach seems to be emerging as afavoured approach that guards against the wellknown statistical risks of failure inherent in theindividual candidate approach.

IPPPH also recognizes that the informationgathering and analysis conducted for this meetingdid not necessarily cover all the portfolio-based PDPPPs that probably should be included. Apologiesare offered where necessary and those omitted areinvited to supply the information that will permit

A N N E X 3 A . B A C K G R O U N D O N T H E P R O D U C T D E V E L O P M E N T P U B L I C - P R I V A T E P A R T N E R S H I P S U N D E R C O N S I D E R A T I O N

In the last decade, there has been a significant expan-sion of so-called ‘public-private partnerships’ (PPPs)

addressing the health problems of low- and middle-income countries (LMICs).1 The Initiative on Public-Private Partnerships for Health (IPPPH) has identifiedalmost 100 such partnerships which include significantinvolvement of pharmaceutical or other health prod-uct companies. These can be grouped according to theirprincipal purpose as follows:

• Generating basic knowledge/research• Product development (PD)• Improvement of access to health products (‘ac-

cess’ PPPs)• Global coordination mechanisms including fund-

ing vehicles• Strengthening of health services• Public education and advocacy• Regulation, quality assurance and standards

Figure 1 below shows the rise over a period of 30 yearsin the overall field and specifically for PD PPPs, ‘ac-cess’ PPPs and global coordinating mechanisms.

In Appendix A, IPPPH lists partnerships in particu-lar categories. Some have ancillary as well as principalfunctions. (See also: www.ippph.org)

Some product development partnerships (PDPPPs) are historical. Among those currently operat-ing, a rough distinction based on general strategy canbe made which helps in keeping the upcoming work-shop manageable and focused on broad strategic is-sues.

Some PD PPPs, as a deliberate strategy, opt to fos-ter the simultaneous development of a number of can-didate products and chose these by surveying theirchosen field. In its most rigorous implementation thisportfolio management approach mimics that used in

1 A widely accepted and consistently used definition of public-private partnerships for health remains elusive. The term issometimes used (perhaps inappropriately) to cover the increasein private sector delivery of health services (the rules for whichare solely government controlled) and also (more appropri-ately) for action for health in LMICs by non-health sector busi-nesses (see Widdus, R. Public-private partnerships needthoughtful consideration. Bulletin of the World Health Organi-zation 2003, 81(4) 235).

2 Project-based PD PPPs also vary considerably. Some focus onessentially proven technologies (e.g., Meningitis A VaccineProject). Others in the early stages of product development –like the early candidates in portfolios – have a high statisticalchance of failing.


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them to be included in future attempts to createcomprehensive categories of such ventures.

Appendix C contains abstracts on each of the PD PPPsconsidered to fostering a range/portfolio of candidateproducts (for more details, see Partnership Databaseat: www.ippph.org). A description of BIO Ventures forGlobal Health is included (Appendix C), as this wasemerging as the meeting was planned. It is not, how-ever, included in the analyses conducted for the meet-ing (e.g., Towse et al, Annex 9a; Sander and Widdus,Annex 9b) as it was not fully operational at that time.

Appendix D contains some examples of project-based PD PPPs.

The background papers by Sander and Widdus (An-nex 9b) and Towse et al (Annex 9a) give details of thevariations among the PD PPPs under consideration.

Roy WiddusProject Manager

Initiative on Public-Private Partnerships for HealthGeneva, Switzerland

APPENDIX A

Public-Private Partnerships for health in low- andmiddle-income countries by principal functionGenerating basic knowledge/researchSingle Nucleotide Polymorphisms Consortium Ltd

(SNP)

Product developmentAction TB Programme (ATBP) (Historical)Aeras Global Tuberculosis Vaccine Foundation (Aeras)Artesunate Suppository for Emergency Treatment of

Severe Malaria (Artesunate)BIO Ventures for Global Health (BVGH)Consortium for Industrial Collaboration in Contracep-

tive Research (CICCR)Contraceptive Research and Development (CONRAD)Dengue Vaccine Project (DVP)Drugs for Neglected Diseases initiative (DNDi)European Malaria Vaccine Initiative (EMVI)Foundation for Innovative New Diagnostics (FIND)Gates Foundation/University of North Carolina

Partnership for the Development of New Drugs(GFUNC)

Figure 1. PPPs by type of approach between 1974 and 2003

Source: IPPPH Partnerships Database: www.ippph.org

4

3.5

3

2.5

2

1.5

1

0.5

0

Num

ber o

f PPP

s

1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2004Years

IMPROVING ACCESS

5

4

3

2

1

0

Num

ber o

f PPP

s

1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2004Years

PRODUCT DEVELOPMENT

3

2.5

2

1.5

1

0.5

0

Num

ber o

f PPP

s

1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2004Years

GLOBAL COORDINATING MECHANISM

16

14

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8

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4

2

0

Num

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f PPP

s

1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2004Years

OVERALL PPPs

5 7

Global Alliance for TB Drug Development (TB Alli-ance)

Global Microbicide Project (GMP)Human Hookworm Vaccine Initiative (HHVI)Infectious Disease Research Institute (IDRI)Institute for OneWorld Health (IOWH)Intercompany Collaboration on AIDS Drug Develop-

ment (ICCADD) (Historical)International AIDS Vaccine Initiative (IAVI)International Partnership for Microbicides (IPM)Japanese Pharmaceutical, Ministry of Health, WHO

Malaria Drug Partnership (JPMW)LAPDAP Antimalarial Drug Development (LAPDAP)Lassa Fever Initiative (LFI)Malaria Vaccine Initiative (MVI)Medicines for Malaria Venture (MMV)Meningitis C Vaccine Development and Supply in the

UK (Historical)Meningitis Vaccine Project at WHO/PATH (MVP at

PATH)Microbicides Development Programme (MDP)Norplant, Development of (ND) (Historical)Pediatric Dengue Vaccine Initiative (PDVI)Pneumococcal Vaccine Accelerated Development and

Introduction Plan (PneumoADIP)Syringes – Autodestruct, Development of (Historical)TropivalTuberculosis Diagnostic Initiative (TBDI) (Historical)Vaccine Vial Monitors (VVM), Development of (His-

torical)

Improvement of access to health productsAccelerating Access Initiative to HIV Care (AAI)African Programme for Onchocerciasis Control

(APOC)Children’s Vaccine Programme at PATH (CVP at

PATH)Concept Foundation (FC)Diflucan Partnership Program (Diflucan)Eli Lilly Multi-Drug Resistant Tuberculosis Partner-

ship (MDR-TB)GlaxoSmithKline African Malaria Partnership (GSK-

AMP)Global Alliance for the Elimination of Lymphatic

Filariasis (GAELF)Global Alliance to Eliminate Leprosy (GAEL)

Global Guinea Worm Eradication Program (GWEP)Global Polio Eradication Initiative (GPEI)International Trachoma Initiative (ITI)Malarone Donation Program (Malarone) (Historical)Maternal and Neonatal Tetanus, Global Elimination

of (MNT)Mectizan Donation Program (Mectizan)Mother-to-Child-Transmission-Plus Initiative (MTCT-

Plus)MSF Campaign for Access to Essential MedicinesNetMark PLUS, a Regional Partnership for Sustain-

able Malaria Prevention (NetMark PLUS)Onchocerciasis Control Programme in West Africa

(OCP) (Historical)Oral Rehydration Salts (ORS) Commercialization in

Bolivia (Historical)Praziquantel Manufacturing Project (Historical)UNAIDS Anti-Retroviral Drug Access Programme

(UNAIDS-Industry) (Historical)UNFPA Contraceptives Access Project (UNFPA/In-

dustry)Viramune® Donation Programme (VDP)WHO Programme to Eliminate Sleeping Sickness

(WPESS)WHO/Novartis Coartem® (Coartem)

Global coordinating mechanisms including funding vehiclesChildren’s Vaccine Initiative (CVI) (Historical)Global Alliance for Improved Nutrition (GAIN)Global Alliance for Vaccines and Immunization (GAVI)Micronutrient Initiative (MI)Roll Back Malaria Global Partnership (RBM)Safe Injection Global Network (SIGN)Stop TB Partnership (Stop TB)The Global Fund to Fight AIDS, Tuberculosis and

Malaria (The Global Fund)Vaccine Fund (VF)Vision 2020 (V2020)Vitamin A Global Initiative (VITA)

Strengthening of health servicesAfrican Comprehensive HIV/AIDS Partnerships

(ACHAP)Alliance for Health Policy and Systems Research

(AHPSR)Global Campaign for Microbicides (GCM)



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Global Elimination of Trachoma, Alliance for the (GET2020)

International Partnership Against Aids in Africa(IPAAA)

Multilateral Initiative on Malaria (MIM)Secure the Future (SF)Step Forward Program (SFP)Strategies for Enhancing Access to Medicines (SEAM)

at Management Sciences for Health (MSH)

Public education and advocacyAlliance for Microbicide Development (AMD)Corporate Council on Africa (CCA)Global Business Coalition on HIV & AIDS (BGC)Global Public-Private Partnership for Hand Washing

with Soap (GPHW)Health InterNetwork (HIN)Hope for African Children Initiative (HACI)International Programme on Chemical Safety (IPCS)Vitamin A Global Initiative (VITA)

Regulation, quality assurance and standardsInternational Conference on Harmonisation of

Technical Requirements for Registration of Pharma-ceuticals for Human Use (ICH)

Global Reporting Initiative (GRI)Pharmaceutical Security Institute (PSI)WHO-Pharmaceutical Industry Associations-NGO

Anti-Counterfeit Drug Initiative (ACDI)

APPENDIX B

Product development public private partnershipsMulti-candidate/portfolio-based PD PPPs for neglecteddiseasesAeras Global Tuberculosis Vaccine Foundation (Aeras)BIO Ventures for Global Health (BVGH)Drugs for Neglected Diseases initiative (DNDi)European Malaria Vaccine Initiative (EMVI)Foundation for Innovative New Diagnostics (FIND)Global Alliance for TB Drug Development (TB Alli-

ance)Global Microbicide Project (GMP) (more data being

sought)Human Hookworm Vaccine Initiative (HHVI)Institute for OneWorld Health (IOWH)International AIDS Vaccine Initiative (IAVI)

International Partnership for Microbicides (IPM)Malaria Vaccine Initiative (MVI)Medicines for Malaria Venture (MMV)Microbicides Development Programme (MDP)Pediatric Dengue Vaccine Initiative (PDVI)Pneumococcal Vaccine Accelerated Development and

Introduction Plan (Pneumo-ADIP)Rotavirus Vaccine Accelerated Development and In-

troduction Plan (Rotavirus-ADIP)South African AIDIS Vaccine Initiative (SAAVI)

Examples of project-based PD PPPs for neglected diseasesArtesunate Suppository for Emergency Treatment of

Severe Malaria (Artesunate)Dengue Vaccine Project (DVP)Gates Foundation/University of North Carolina Part-

nership for the Development of New Drugs(GFUNC)

Infectious Disease Research Institute (IDRI) (moredata being sought)

Japanese Pharmaceutical, Ministry of Health, WHOMalaria Drug Partnership (JPMW) (more data be-ing sought)

LAPDAP Antimalarial Drug Development (LAPDAP)Meningitis Vaccine Project at WHO/PATH (MVP at

PATH)Lassa Fever Initiative (LFI) (In early development,

therefore uncertain)

NB. Each of the projects in portfolios also represents anindividual project-based PD-PPP.

PD PPPs for other health problemsConsortium for Industrial Collaboration in Contracep-

tive Research (CICCR)Contraceptive Research and Development Program

(CONRAD)

Historical PD PPPs for neglected diseasesAction TB Programme (ATBP)Meningitis C Vaccine Development and Supply in the

UK (MCVD)Norplant, Development of (ND)Syringes – Autodestruct, Development ofTuberculosis Diagnostic Initiative (TBDI)Vaccine Vial Monitors, Development of (VVM)

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APPENDIX C

PD PPPs planning to foster a range of candidateproductsAeras Global TB Vaccine Foundation (Aeras)The Aeras Global TB Vaccine Foundation (formerlyknown as the Sequella Global Tuberculosis Founda-tion) was founded in 1997 to help develop new con-cepts and tools to control the global TB epidemic. In1999 the Foundation received a five-year, US$25 mil-lion grant from the Bill & Melinda Gates Foundationto fund the TB Vaccine Collaboration. The organiza-tion now focuses exclusively on developing newvaccines against tuberculosis and ensuring that theyare distributed to all who need them. Major fundingcomes from the Bill & Melinda Gates Foundation.Aeras is the only organization solely dedicated to de-veloping a better way to vaccinate against TB. Work-ing in collaboration with individual scientists, academicinstitutions, industry and government agencies in theUnited States and Europe, as well as South Africa andother developing countries, Aeras aims to bring sev-eral of the leading TB vaccine candidates to Phase I, IIand III clinical testing over the next decade and tolicense and manufacture at least one new TB vaccinefor worldwide distribution within 10 years.

BIO Ventures for Global Health (BVGH)BIO Ventures for Global Health (BVGH), launchedin June, 2004, was formed to accelerate the develop-ment, distribution and accessibility of biotechnologyproducts that address the world’s most devastating andneglected diseases. Spun out the Biotechnology Indus-try Organization (BIO) with initial support from theBill & Melinda Gates Foundation and RockefellerFoundation, BVGH is taking a market-based approachto attract biotech innovators to tackle these globalhealth challenges. The organization is premised onthree beliefs:

• Biotech innovators have the tools, developmentexpertise and product focus to develop much-needed products for these populations;

• These companies can and will take on these chal-lenges if the market incentives are right; and

• Sufficient market incentives must be in place toattract quality innovators.

Over the next year, BVGH is embarking on two com-plementary and highly leveraged activities that encour-age the private sector to invest their own resourcestoward global health R&D. First, BVGH is develop-ing a series of product specific business cases to iden-tify viable market opportunities where they exist andmap regulatory, licensing and distribution strategiesto get successful products to those that need them.Second, BVGH will build industry and donor supportfor advanced markets or other incentive mechanismsnecessary to supplement insufficient markets. BVGHpublishes the quarterly BVGH Report and maintainswww.bvgh.org as a resource for all innovators inter-ested in global health product development.

Drugs for Neglected Diseases initiative (DNDi)Launched on 3 July 2003, DNDi is a new not-for-profit drug research organization, with a secretariatbased in Geneva, Switzerland. This new PPP is the firstof its kind to focus exclusively on some of the world’smost neglected diseases: human African trypanosomia-sis (sleeping sickness), leishmaniasis and Chagas dis-ease. DNDi will engage in targeted drug R&D for themost neglected diseases. It plans to spend aroundUS$250 million over the next 12 years to develop sixor seven new drugs. It will also encourage the creationof global networks of research facilities and will helpstrengthen their research capabilities.

European Malaria Vaccine Initiative (EMVI)EMVI is an international programme of the EuropeanCommission and Member States of the EuropeanUnion (EU)established in 1998 at the Centre for In-ternational Health, University of Bergen, Norway. Ithas secretariats in Copenhagen, Denmark and Paris,France. EMVI’s mission is to contribute to the globalefforts to control malaria by providing a mechanismfor accelerated development and clinical trials of ma-laria vaccines in both Europe and developing coun-tries, and by promoting affordability and accessibilityof malaria vaccines in developing countries. EMVI pro-vides a mechanism to:

• facilitate concerted interaction between a Euro-pean Commission core activity and EU MemberStates’ investments

• accelerate the process of bringing promising re-search results, i.e. experimental malaria vaccines,



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via limited industrial production to clinical evalu-ation in European volunteers and subsequentlyto clinical evaluation in developing countries inclose collaboration with trials networks in ma-laria endemic areas.

In a joint effort announced in June 2001, EMVI hasjoined forces with the Malaria Vaccine Initiative (MVI)and USAID’s Malaria Vaccine Development Program(USAIDMVDP) via a memorandum of understand-ing, in order to plan how to break through technicaland financial barriers to vaccine development. They willalso share information useful for the design of clinicaltrials and malaria vaccine development. A memoran-dum of intent has since been signed with WHO.

Foundation for Innovative New Diagnostics (FIND)The Foundation for Innovative New Diagnostics(FIND) was launched on 22 May 2003 at the WorldHealth Assembly in Geneva. This is a new, independ-ent, non-profit foundation based in Geneva, which willwork in close collaboration with WHO, the SpecialProgramme for Research and Training in Tropical Dis-eases (TDR), academia, the diagnostics industry andother organizations. FIND is building on the successof a former TDR programme, the tuberculosis diag-nostics initiative (see TBDI profile at www.ippph.org -Partnerships Database). With additional funding fromthe Bill & Melinda Gates Foundation, FIND will beable quickly to turn methods into products, untestedproducts into fully evaluated products, and promisingtests into tools with demonstrated impact and feasibil-ity. FIND will apply the latest biotechnology innova-tions to develop and validate high-quality, yet affordablediagnostic tests, through the R&D pipeline, for dis-eases of the developing world. Ultimately, FIND aimsto create a model for public action that resolves thecurrent failure of market forces. The Gates Founda-tion has committed up to US$30 million over the nextfive years to the initiative. FIND will focus initially onTB diagnostics, in order to replace the current cum-bersome sputum test for TB with a faster, more practi-cal test to detect the disease, including drug resistantforms, and eventually move onto other infectious dis-eases.

Global Alliance for TB Drug Development (TB Alliance)The Global Alliance for TB Drug Development is aninternational PPP accelerating the discovery and de-velopment of faster-acting and affordable drugs to fighttuberculosis. The TB Alliance builds and manages aportfolio of promising compounds with partners world-wide and invests in platform technologies that improvethe environment for TB drug development. By pro-viding staged funding, expert scientific and manage-ment guidance, and clear pre-defined milestones, theTB Alliance can ensure the rapid development of com-pounds. The TB Alliance pursues intellectual propertyrights to ensure that new drugs are affordable to andadopted by those most in need. The promise of TBcontrol efforts will only be met fully when health-careworkers are given the best tools that modern sciencecan deliver.

Global Microbicide Project (GMP)In 2000, CONRAD established the GMP to help de-velop new microbicidal agents that specifically addressthe needs and perspectives of women. The main ob-jective of this project is to develop vaginal methodsthat would protect women against sexually transmit-ted infections (STIs), including HIV/AIDS. The GMPcan provide funds for both pilot and major projects.Although there is no requirement for cost sharing byan industrial partner, it is strongly encouraged. Atpresent, GMP funding comes solely from the Bill &Melinda Gates Foundation in the form of a US$25million grant to expedite microbicide development.

Human Hookworm Vaccine Initiative (HHVI)The Albert B. Sabin Vaccine Institute (SVI) is a UnitedStates non-profit educational and research organiza-tion dedicated to saving lives by stimulating the devel-opment of new vaccines, and increasing domestic andglobal immunization rates. Its programmes advancedevelopment of new vaccines and improved ways toproduce and administer them. Founded in 1993, SVIis committed to continuing the work of polio vaccinedeveloper Dr Albert Sabin, who envisioned the enor-mous potential of vaccines to prevent deadly diseases.The Institute currently operates from three sites: thenational headquarters in New Canaan, Connecticut;the international programmes/public affairs office inWashington DC; and the HHVI headquarters in

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Rockville, Maryland. The Institute is developing a vac-cine to prevent an infection that afflicts almost 1 bil-lion individuals, and is the leading cause of anaemiaand malnutrition in the developing world. The HHVI,with the generous assistance of the Bill & Melinda GatesFoundation, sponsors vaccine research and develop-ment, under an US$18 million commitment started inApril 2000. Research is conducted by vaccinologist,Dr Peter Hotez, a Senior Fellow at the Sabin Instituteand the Professor and Chair of the Department ofMicrobiology and Tropical Medicine at The GeorgeWashington University. The research laboratories arelocated at The George Washington University Medi-cal Center. Other aspects of vaccine development arebeing outsourced to several academic and industrialorganizations.

Institute for OneWorld Health (IOWH)The Institute for OneWorld Health (IOWH) is a tax-exempt non-profit pharmaceutical company launchedin 2000 and based in San Francisco, California. Itsmission is to develop safe, effective and affordable newmedicines for diseases affecting people in the develop-ing world, for which therapies either do not exist orare inadequate. Staffed with pharmaceutical scientistswith international drug development and regulatoryexpertise, IOWH identifies promising drug and vac-cine candidates and executes preclinical development,with the goal of regulatory approval of therapies in themost affected countries. Throughout the developmentprocess, from discovery to clinical trial to regulatoryapproval and manufacturing, IOWH collaboratesclosely with a range of global health players, includingWHO, major research universities, the Walter ReedArmy Institute of Research, the National Institutes ofHealth and the various pharmaceutical companies.IOWH seeks public sector funds to pursue projects thatcould be promising for the developing world but whichmay not attract private investment funds. Once newdrugs are approved for use by regulatory agencies,manufacturing and distribution are outsourced to qual-ity corporations in the developing world to maintainIOWH’s focus on drug development. It is anticipatedthat differential pricing will be applied to all of IOWH’sdrugs, to ensure affordability.

International AIDS Vaccine Initiative (IAVI)IAVI is a United States tax-exempt, not-for-profit sci-entific organization established in 1996 to ensure thedevelopment of safe, effective and accessible preventa-tive HIV vaccines for use throughout the world. IAVIis a collaborating centre of UNAIDS and works withboth public and private sector organizations in pursu-ing its mission. IAVI’s work focuses on four areas: cre-ating global demand for AIDS vaccines throughadvocacy and education; accelerating scientific progress;encouraging industrial involvement in AIDS vaccinedevelopment; and assuring global access. IAVI fundsand sponsors fast-tracked product development andclinical testing of promising AIDS vaccine candidatesdeveloped for the countries most affected by the dis-ease. IAVI’s major financial supporters include the Bill& Melinda Gates Foundation; the Rockefeller, Sloanand Starr foundations; the World Bank; Becton,Dickinson & Co.; the Canadian International Devel-opment Agency (CIDA); and the governments of theNetherlands, United Kingdom, United States, Ireland,Denmark, Norway and Sweden. IAVI has now securedcommitments totalling US$310 million, towards a goalof US$655 million by 2008.

International Partnership for Microbicides (IPM)The International Partnership for Microbicides (IPM)is a PPP formed in 2002 to accelerate the discovery,development and accessibility of microbicides to pre-vent transmission of HIV, especially among women inlow-resource settings. Through review andprioritization, the IPM provides resources and exper-tise for targeted, milestone-driven projects in its coreareas of product development and access. IPM is sup-porting development initiatives across the microbicidepipeline, especially agents with new modes of action,and investing in efforts to provide the field with sharedtechnologies (e.g., novel long-acting formulations) andresources (e.g., expanded clinical research capacity.)IPM is also identifying and supporting policy and pro-grammatic initiatives that will facilitate rapid approvaland introduction once effectiveness has been demon-strated; initial work is in the areas of financing, regula-tory affairs and country preparedness. Finally, IPMworks to raise awareness and resources for microbicidedevelopment. A recent analysis conducted by expertsat the London School of Hygiene and Tropical Medi-



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cine, based on real data from 73 low-income coun-tries, concluded that a 60% efficacious microbicide,used by 20% of people easily reached through existinghealth services, in one-half of the occasions when con-doms are not used, would avert 2.5 million new infec-tions over three years in women, children and men.

Malaria Vaccine Initiative (MVI)Based in Rockville, Maryland and Seattle, Washing-ton, MVI was started with seed funding of US$50million from the Bill & Melinda Gates Foundation inJune 1999. MVI is administered by Program for Ap-propriate Technology in Health (PATH), aUnitedStates tax-exempt, not-for-profit organization. MVI’smission is to accelerate the development of malariavaccines and ensure their availability in the developingworld. Funds are directed to vaccine development part-nerships with industry, biotechnology firms, govern-ment agencies and academia. Each project may supportprocess development, production and/or clinical tri-als in malaria-endemic regions. Technical advisorygroups and PATH’s board guide MVI. Partners in-clude malaria experts around the world, governmentagencies, academia, public and private research insti-tutions, and vaccine producers. Business development,communication, and policy activities support the vac-cine development partnerships and seek to improve theenvironment for malaria vaccine development and in-troduction.

Medicines for Malaria Venture (MMV)The Medicines for Malaria Venture (MMV) was cre-ated in 1999 as a Geneva-based not-for-profit organi-zation under Swiss law, to discover, develop and delivernew antimalarial drugs that are effective and afford-able. MMV receives funding and support from thefollowing organizations: the Bill & Melinda GatesFoundation; ExxonMobil Corporation; Global Forumfor Health Research; International Federation of Phar-maceutical Manufacturers Associations (IFPMA);WHO; the Rockefeller Foundation; the World Bank;Roll Back Malaria global partnership; TDR; the UnitedKingdom’s Department for International Development(DFID), Swiss Agency for Development and Coop-eration, the Netherlands Minister for DevelopmentCooperation and the Wellcome Trust. MMV also re-ceives contributions in-kind, such as management ex-

pertise, access to chemical libraries, high throughputscreening and data handling from pharmaceutical com-panies, biotech firms, universities and research insti-tutes. MMV’s goal is to identify one new drug everyfive years with the first one by 2010. In order to reachits goal, MMV has built up the largest antimalarial drugresearch and development portfolio in history, whichcurrently consists of 21 projects in different develop-mental stages. Within its 11 discovery and 10 devel-opment projects, MMV has eight completely newtherapeutic targets in the pipeline. The clinical devel-opment projects are gaining momentum and severalof preclinical projects are set to move into clinical stud-ies in 2004. Its desired full operating annual budget isUS$30 million.

Microbicides Development Programme (MDP)MDP is a partnership to accelerate the evaluation anddevelopment of vaginal microbicides for the preven-tion of HIV transmission. Established in 2001, theprogramme is funded by DFID and administered bythe Medical Research Council Clinical Trials Unit andImperial College London. The central goal of the part-nership is to complete a phase III effectiveness trial ofcandidate microbicides in multiple sites in sub-Saha-ran Africa. Currently, feasibility studies to estimate in-cidence and assess condom usage are currently beingconducted in Tanzania, Zambia, Uganda and three sitesin South Africa. Furthermore, MDP aims to developnew products to enter safety studies in the United King-dom and Africa; to conduct social science research intothe acceptability and possible barriers concerning theuptake of the products; and to facilitate marketing andaccess to a successful microbicide.

Pediatric Dengue Vaccine Initiative (PDVI)The Pediatric Dengue Vaccine Initiative (PDVI) rep-resents a public-private effort to raise awareness of theneed for and accelerate the development of a denguevaccine that is appropriate, safe and accessible to poorchildren in endemic countries. Dengue is a mosquito-borne viral disease that affects tropical regions aroundthe world. Every year, in addition to tens of millionsof cases of severe dengue fever, an average of 500,000people, mostly children, are hospitalized with denguehaemorrhagic fever with high case fatality rates. Nospecific, effective treatment is available and vector-con-

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trol strategies have been insufficient to counter thepandemic. This led the Rockefeller Foundation andthe International Vaccine Institute to convene a meet-ing in 2001 to focus on the challenges and opportuni-ties for the development of a paediatric dengue vaccine.The meeting, and related working-group processes,have energized the field and built unprecedented mo-mentum to bring about a coordinated global effort.This coincides with a 2002 resolution by the WorldHealth Assembly that stresses the negative impact ofdengue on health and development.

Pneumococcal Vaccines Accelerated Development andIntroduction Plan (PneumoADIP)The Pneumococcal Vaccines Accelerated Developmentand Introduction Plan, PneumoADIP, is an independ-ent group located at the Johns Hopkins School ofPublic Health and funded by GAVI. Its mission is toimprove child health by accelerating the evaluation ofand access to new life-saving pneumococcal vaccinesfor the world’s poorest children. PneumoADIP aimsto shorten the time lag between the use of a new vac-cine in rich countries and its use in poor countries byworking to achieve a sustainable, affordable supply ofquality vaccines by reducing the uncertainty of demandfor the vaccine in the world’s poorest countries.

Rotavirus Vaccine Programme (RotaADIP)In 2003, with funding from GAVI and the VaccineFund, PATH established the Rotavirus Vaccine Pro-gramme. RotaADIP is a limited liability company ofPATH. Its mission is to reduce child morbidity andmortality from diarrhoeal disease by accelerating theavailability of rotavirus vaccines appropriate for use indeveloping countries.

South African AIDS Vaccine Initiative (SAAVI)In 1999, it was decided that South Africa should developits own HIV/AIDS vaccine. This led to the formation ofthe South African AIDS Vaccine Initiative (SAAVI), anational body coordinating the research, developmentand testing of HIV/AIDS vaccines in South Africa withthe aim of producing an affordable, effective and lo-cally relevant preventative HIV/AIDS vaccine. SAAVIreceives funding from the South African government,Eskom and international organizations. SAAVI is basedat the South African Medical Research Council.

APPENDIX D

Examples of PD PPPs based on specificcandidate productsInfectious Disease Research Institute (IDRI)A joint industry research programme of the IDRI,which is a United States, tax-exempt, not-for-profitscientific organization supported by public funds. In1994 IDRI established a collaborative partnership withCorixa Corporation, an R&D-based biotechnology andvaccine company. The goal of the partnership is tooptimize the development of vaccines, therapeutics anddiagnostics against leishmaniasis and diagnostics againstdiseases of developing countries. In March 2000, IDRIreceived a US$15 million grant from the Bill & MelindaGates Foundation to fund their ongoing effort to de-velop a vaccine to prevent and treat leishmaniasis. Thisprogramme is being carried out in collaboration withCorixa, and supported in part by funding from theNational Institutes of Health . In January 2003, IDRIand Corixa announced initiation of a US-based phaseI clinical trial of a candidate vaccine against leishma-niasis.

Lapdap Antimalarial Product Development (LAPDAP)A joint research agreement was signed in March 2001between WHO through its United Nations Develop-ment Programme (UNDP)/World Bank/WHOSpecial Programme for Research and Training in Tropi-cal Diseases (WHO/TDR) and GlaxoSmithKline todevelop a new effective oral treatment for uncompli-cated malaria, primarily for use in sub-Saharan Africa,at preferential prices for public health programmes. Theaim is to develop chlorproguanil-dapsone (Lapdap™)for regulatory submission as a safe alternative to chlo-roquine and sulfadoxine-pyrimenthamine (SP) fortreatment of malaria caused by the Plasmodiafalciparum malaria parasite in Africa. To date, clinicalphase III trials on LAPDAP have been conducted inGabon, Kenya, Malawi, Nigeria and Tanzania. Fund-ing is provided by WHO/TDR, GSK and DFID. Thefile was submitted to the British Medicines andHealthcare Products Regulatory Agency (MHRA) inNovember 2002. A marketing authorization was is-sued by the MHRA in July 2003. The dossier has beensubmitted to many African national authorities, andmarketing approval has been granted in some coun-



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tries. Lapdap™ has been launched commercially in sev-eral countries.

Gates Foundation/University of North Carolina Partnershipfor the Development of New Drugs (GFUNC)GFUNC was established in 2000 with a US$15.1 mil-lion five-year grant. The overall goal of this partner-ship is to develop potent, safe, orally active andeconomical new drugs to treat African trypanosomia-sis and leishmaniasis. This partnership has brought to-gether experts, researchers and clinicians from aroundthe world, with academia, governments internationalorganizations, private institutions and industry all in-volved in the field of clinical development and drugdiscovery therapies to fight these diseases that are kill-ing and infecting millions of people in African-endemiccountries.

Meningitis Vaccine Project at WHO/PATH (MVP)MVP is a partnership between WHO and the Programfor Appropriate Technology in Health (PATH) cre-ated with the technical advice of the United States’Centers for Disease Control and Prevention, to elimi-nate epidemic meningitis in sub-Saharan Africa. Theproject aims to develop a viable serogroup A menin-gococcal conjugate vaccine within five years byleveraging the strengths of the public and private sectorsto commission the development of a vaccine that wouldnot otherwise be commercially feasible. The project isa ten-year programme, with initial funding of US$70million from the Bill & Melinda Gates Foundation inMay 2001, which will ensure the delivery of this vac-cine through mass and routine immunization pro-grammes for children and adults in affected countries.Key partners include vaccine companies and interna-tional and national groups working to prevent and re-spond to meningococcal meningitis epidemics in Africa.

For other examples, please see the PartnershipsDatabase at www.ippph.org.

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ANNEX 3B

Background on the concept of the workshopProposed workshop: Combating diseases associated with poverty:

Financing strategies for product development and thepotential role of public-private partnerships

that can assist implementation, such as health servicesnongovernmental organizations (NGOs).

While some tools exist for combating many diseasesand other health problems associated with poverty,better tools (vaccines, drugs, diagnostics, topicalmicrobicides, contraceptives, etc.) are needed for al-most all and in particular HIV/AIDS, malaria andtuberculosis. In some cases there is little prospect ofmeeting the MDGs without new or better products.Developing and putting into use these new or improvedtools entails a complex, multi-step process of basic andtargeted research, product development including clini-cal efficacy trials in disease-endemic countries, manu-facturing process development, regulation, pilot/demonstration projects and procurement for routineutilization. In this ‘chain’, many actors and funderscan play a role. However, for products to combat healthproblems that predominantly or exclusively affect poorpeople around the world, there is little motivation forcommercial companies independently to apply theirexpertise in product development and manufacture.The risks and costs, including opportunity costs, out-weigh the low potential future revenues. There has beenmuch discussion over the last few years of so-called‘push’ interventions (to reduce the costs and risks toindustry) and ‘pull’ interventions (to ensure a greatermarket), but relatively little substantive action hasemerged in the public policy arena. Welcome excep-tions to this generalization include some new WorldBank financing mechanisms, the Vaccine Fund (VF),associated with the Global Alliance for Vaccines andImmunization (GAVI), and the Global Fund to FightAIDS, Tuberculosis and Malaria (GFATM) which givesome hope of procurement and application of new andbetter products. The latter two however both need moreresources to meet demand from the poorer countries.

A N N E X 3 B . B A C K G R O U N D O N T H E C O N C E P T O F T H E W O R K S H O P

Summary

The Initiative on Public Private-Partnerships forHealth,1 a component of the Global Forum for

Health Research, is organizing a workshop to explorethe potential contributions of public-private partner-ships (PPPs) for product development (PD) to com-bating diseases associated with poverty. The meetingwill consider in particular the roles, relationships, ac-tivities, ‘added-value’ and financing needs of those PDPPPs specifically utilizing a ‘portfolio management ap-proach’. The workshop will also cover the context inwhich such ventures operate, namely between morefundamental research and new product utilization, andthe activities by various other players which are neces-sary to support their ultimate success.2

BackgroundA wide range of organizations in both public andprivate sectors have an interest in contributing to thereduction of diseases associated with poverty in devel-oping countries, which is a major component of theMillennium Development Goals (MDGs). Obviously,the responsibility to organize the delivery of healthservices falls ultimately to the respective governments,but in developing and supplying health productsneeded in poorer countries, many other players areinvolved. These organizations include funders such asmultilateral and bilateral aid agencies, private philan-thropic foundations, scientific agencies and organiza-tions (including pharmaceutical companies), and others

1 The Initiative on Public-Private Partnerships for Health(IPPPH) was established in 2000, under the Geneva-basedGlobal Forum for Health Research, to monitor, analyze andsupport ventures in public-private collaboration to reduce glo-bal health inequities associated with poverty.

2 This proposal was initially distributed in the latter half of 2003.


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Over the last decade, and particularly in the last threeto four years, there has, however, been significantgrowth in the number of groups attempting to de-velop tools to combat the diseases and other healthproblems associated with poverty, through so-called‘public-private partnerships’ engaging commercialpharmaceutical companies.

This phenomenon arises from increasing recogni-tion that the expertise to turn scientific research intouseful health products (drugs, vaccines, diagnostics,contraceptives, microbicides, impregnated bed-nets,etc.) resides overwhelmingly in commercial, privatesector industry, but that products to combat the healthproblems that predominantly afflict the poor are notcommercially attractive, compared to those that wouldbe used by more affluent populations.

PPPs are inter alia a way of engaging commercialexpertise through lowering the risk and costs to in-dustry. However, in addition to paid contributions, theprivate sector often contributes additional in-kind re-sources (see IPPPH, 2002).1 Hence, the total cost maybe less than ‘full-price’ contracting for all activities, evenassuming that companies would divert human andother resources even if cash only for R&D was on of-fer, without other factors that PPPs bring to the col-laboration.

Public-private partnerships do not simply pass onresources to industry but also become engaged in or-chestrating the linkages necessary to channel basic re-search concepts through to improved health for thepoor. In this role they can shorten the time requiredto apply investments in basic research to health. Theyalso engage in advocacy to raise awareness of healthneeds among poor populations and in so doing, mobi-lize moral support and new resources to this goal.

These PPPs usually attempt to keep a range of prod-ucts at different stages of development moving downthe ‘development’ pipeline’. This so-called ‘portfoliomanagement approach’ (PMA) is adapted from busi-ness methods in the pharmaceutical industry. It is de-rived to maximize statistically the likelihood of ultimatesuccess, given probable candidate product failures thatare predictable, statistically if not individually. The PMA

has cross-project learning synergies and particular im-plications for financing requirements. The financingneeds of portfolio management are fundamentally dif-ferent to the project-by-project funding approach usu-ally practised for more basic research.

A limited range of funders, including bilateral de-velopment agencies and foundations (such as the Bill& Melinda Gates Foundation and the RockefellerFoundation), has invested significantly in product de-velopment PPPs in the health sector – believing theyoffer a new approach. Other potential funders havechosen not to make such a commitment, at least atthis point. It is not clear whether they have just de-layed considering such funding or have so far unan-swered questions regarding the role that PD PPPs canplay, the rationale for them or their operations. Otherfunders may indeed play a role mostly in financing re-search that feed the PPP pipelines or financing pro-curement, and thus ensuring the ultimate utilizationof their new products. In all cases there would be con-siderable benefit in better understanding the potentialroles and links necessary to ensure an efficient transferof promising candidate concepts/products down thedevelopment chain, preferably with some assurance ofmechanisms and funding for eventual uptake

A number of PD PPPs have now accumulated a fewyears’ experience. It is, therefore, a reasonable timefor an interim assessment of the approach, its costs,possible alternatives and overall lessons learned to date.Options for further innovative financing need to beconsidered in addition to the traditional sources. Ad-ditional topics that also need addressing are:

• What else needs to be in place for PD PPPs ascurrently conceived to do their task effectively?How can links in the chain from research to usebe optimized?

• What tools are available to measure progress intargeted research and product development?

• What are the benefits of assured financing foruptake to interest in product development?

The workshop proposed by IPPPH is an opportunityto deepen and broaden understanding of this funda-mentally new approach and to assess its prospects, costsand implications. It will necessarily include representa-tives of selected PD PPPs to explain their approaches.However, it is not intended to be a means through

1 Kettler H, White K. Valuing Industry Contributions to Public-Private Partnerships for Health Product Development. Geneva:IPPPH, 2003.

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which individual organizations will pursue their ownparticular fund-raising objectives.

The workshop is relevant to all organizations desir-ing to contribute to reducing the global burden of dis-ease associated with poverty, in that better tools tocombat such health problems are needed to assist inachieving most of the MDGs. Organizations thatshould be represented include:

• Bilateral and multilateral aid agencies whetherfunding R&D for health products or health serv-ices delivery

• Philanthropic foundations supporting basic re-search, product development or disease controlprogrammes

• Technical agencies funding research, productdevelopment and/or public health programmes

• Health policy-makers from developing countries• Pharmaceutical companies and PPPs engaged in

product development.

The option is available for funders to convene a satel-lite meeting to consider separately their responses tothe recent creation of a number of PPPs (includingespecially those involved in product development) andthe issues raised in the workshop.

The desired outcomes of the IPPPH workshop are:

• A broader and deeper understanding among par-ticipants of the mode of operations of PPPs forthe development of products to combat devel-oping countries’ neglected health problems andtheir potential roles

• Achievement of consensus (to the extent possi-ble) on actions needed to maximize their poten-tial to contribute to the alleviation of diseasesassociated with poverty

• Identification of questions or issues needing fur-ther clarification

• Establishment of a Follow-up Monitoring Groupto assess the impact of the workshop and pro-pose desirable next steps.

Draft objectives, proposed outputs, proposed partici-pants and a preliminary agenda are provided in thefollowing pages and comments on these would bewelcomed.

The objectives of the workshop• To provide background on the emergence and

operations of PD PPPs for ‘neglected’ health prob-lems:— How did we derive the PD PPP model for

development of pharmaceuticals needed to com-bat diseases associated with poverty?

— How and why did the portfolio managementapproach evolve in industry to maximize statis-tically chances of success?

— Why is it appropriate to not-for-profit PD PPPs?— How is it different to traditional funding for

research projects, e.g. in academia?• To consider how PD PPPs and other players

operate and interact in the ‘chain’ by which sci-entific knowledge is developed and applied forglobal health:

— How can the transition at the research/productconcept to product development interface bebest expedited, specifically in cases where candi-date products have low commercial attractive-ness?

— What else needs to be in place for PD PPPs todo their tasks effectively?

— Beyond portfolio management, what value doPD PPPs add along the product developmentchain?

— What ‘metrics’ can be used for measuringprogress in research and product development?

— How can we best anticipate and ensure the rapiduptake of suitable new products to routine use?

• To assess if innovative financing options for ‘ne-glected products’ exist

• To assess the current financial situation of PD PPPsthat use the PMA, given their need for a ‘criticalmass’ of products in the pipeline for best econo-mies of scale, likelihood of success and cross-projectlearning

• To reassess original predictions of financial require-ments of PD PPPs and predict their future financialneeds

• To evaluate what are the relative costs of investingin alternative approaches to ensuring the develop-ment of products needed to combat diseases associ-ated with poverty (i.e. other than the PD PPPs usingthe PMA)

• To consider what PPPs, various funders, private

A N N E X 3 B . B A C K G R O U N D O N T H E C O N C E P T O F T H E W O R K S H O P


6 8

sector organizations and others should do based oninformation presented and discussions at the work-shop.

Outputs of the workshop and follow-up process• Establishment of a small Follow-up Monitoring

Group (of about six persons drawn from constitu-encies represented at the meeting) to assess actionstaken as a result of conclusions reached at the work-shop and periodically to guide the IPPPH Secre-tariat on desirable next steps

• A report of the workshop presentations and discus-sions, including background papers, disseminatedwidely within three months of the workshop

• Approximately 12 months after the workshop, anexternal evaluation of actions probably resultingfrom the workshop and a summary report on desir-able next steps based on the external evaluation andconsultations with the Follow-up MonitoringGroup.

Potential participants• Funders of research, product development and pub-

lic health programmes (i.e. disease control and healthservices delivery):— Foundations— Bilateral development agencies— Government research funding agencies— Multilateral agencies— Developing country governments

• Representatives of pharmaceutical and ‘biotech’companies and venture capital investors

• Representatives of existing ‘partnerships’ for devel-opment of products needed primarily in developingcountries: from among GATBDD, IAVI, IPM,MMV, MVI, Institute for OneWorld Health, Aeras,FIND and DNDi/MSF, possibly others

• Selected representatives from low-income countries,in which the target health problems are endemic

• Other selected participants.

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ANNEX 4

Purpose of the meeting: Opening RemarksRoy Widdus (Initiative on Public-Private Partnerships

for Health, Geneva, Switzerland)

1. How can we most usefully define and conceptual-ize the ‘field’?• Public health history has repeatedly taught the

lesson that the uptake of appropriate, new prod-ucts does not occur automatically.— Have we learned this lesson? Gargee Ghosh’s

paper (see Background paper 9i.) suggestssome hope in the area of vaccines but effortsin planning new drug introduction are rare

• If the ultimate goal of product development ispublic health impact we must identify and some-one must address potential delays in ‘access’

• Many of the PPPs at the workshop are commit-ted to work on ‘access’ but perhaps we shouldalso be looking for other organizations to play abigger role in ensuring access – particularly as itis usually considered a public sector responsibil-ity

• If the goal is the highest public health return oninvestment (PH-ROI), then we must create acommonly agreed and used way of expressingPH-ROI that expresses potential public healthbenefit incorporating as well the cost to developand deliver the products.

Correctly conceptualizing the problem – as being thepursuit of public health impact – is essential to solvingit; otherwise we just shift the bottleneck, simply creat-ing a bigger backlog of underused products.

2. How to improve understanding, communicationand coordination among implementers and funders?• With products to combat diseases that are not

commercially attractive, we have a multitude ofplayers engaged at many different stages. To besuccessful in a reasonable time we must ensurethat they work more in unison:

A N N E X 4 . P U R P O S E O F T H E M E E T I N G : O P E N I N G R E M A R K S

• There has been a dramatic increase in attention to‘neglected diseases’ in the last five years:— This has occurred on many varied fronts rather

than being the result of a systematic effort— Health in developing countries has gone up the

political agenda, as symbolized by the widely ac-cepted Millennium Development Goals (MDGs)and the creation of Global Fund (GFATM)

— 50% of the MDGs are related to health directlyor indirectly (see Annex 5).

• Prospects for achieving the 2015 targets for theMDGs without new tools to combat diseases asso-ciated with poverty are fairly bleak:— Most resources and discussion about achieving

the MDGs focus on applying existing tools— Available tools must be applied, but for the ma-

jor diseases the array of existing tools is inad-equate and, for the most neglected diseases, thesituation is even worse.

• This meeting pulls together most of the key actorsrelevant to combating neglected diseases more ef-fectively through improving the tools available:— It is, as far as we know, the first time that such a

stellar array of talent has been gathered in oneplace on the specific topic of product develop-ment for neglected diseases

— It can also be unique if we all take off our usualfundraising, donor or industry ‘hats’ and focuson the exchange of information

— This workshop is an exercise in melding differ-ent cultures and different ways of doing busi-ness (but we are not looking for ‘a one-size fitsall’ model).

This is a special opportunity to consider collectivelythree topics that are important to future progress:


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— Along the research-development-access con-tinuum

— Across those engaged in similar activities— Among disease-specific and broader health

system activities.• Shared terminology is desirable but at least un-

derstanding each other’s usage is a start• We learnt in the preparations for the meeting that

individual PPPs see their activities as unique andoften take a while to get used to ways of describ-ing what they do that are not the ones they arefamiliar with

• Better communication and ‘hand-offs’ will be anongoing challenge, so how do we achieve andsustain coordination on these over time?

3. How to make future decisions based on better in-formation?

• Better estimates of the financing needed are partof this process

• What are the other important things that shouldbe tracked?

• What are the important things to analyse further?• How do we define the trade-offs across all the

possible ways to invest available resources?• How do ‘we’ get these things done to high qual-

ity in an impartial manner?

There are many discrete issues that will need to be con-sidered before we can get to consensus on these threeoverarching questions.

The issues can be grouped as those relating to thebroader field and those that relate to the individualproduct development partnership.

We have laid some issues out in the listing that is anattachment in the printed copy of these opening re-marks and the “Questions by Sessions” (see Annex 7).

This meeting will hopefully start consideration ofthese issues – but we should be realistic. Above all thereis no sense among the organizers that we can prescribea perfect model.

It is perhaps more important to decide how to con-tinue the information exchange and analysis than tobelieve that all questions can be decided at this meet-ing. So we have three key challenges to keep in mindfor the closing session:

• How do we define and conceptualize the field?As ending at new product licensure or at publichealth impact? And if ‘access’ is included, what isan appropriate role for PD PPPs in ensuring weget the fullest PH-ROI in developing new toolsfor preventing, diagnosing or treating neglecteddiseases (PH ROI is the surrogate for the ‘pull’of a market)?

• How do we improve communication, exchangeof experience and coordination?

• What needs tracking and analysing?

AttachmentSome of the issues identified in preparationsfor the workshopAt the level of the overall field of products to combat‘neglected diseases’• How should the field be conceptualized? The ana-

lytical frame can be limited to product developmentper se. However, highlighting what is necessary toachieve ‘access’ enables parallel attention to prob-lems that may otherwise create bottlenecks and se-riously impede achieving potential public healthimpact. This attention may best be from others withmore direct ‘downstream’ responsibilities, ratherthan the PD PPPs themselves. But it must occur.

• Can and should the field be ‘managed’ systemati-cally? Gaps in needed product development activi-ties and overlapping PD PPP missions are a causefor concern.

• If ‘management of the field’ is to be attemptedshould this be by funders or by coordination amongimplementers, e.g., PD PPPs, or a combination ofboth?

• How can better coordination among funders andimplementers be achieved:— Along the research-development-access con-

tinuum— Across funders or implementers engaged at

particular steps along the continuum— Among disease-specific and overall health system

players?• How can funders obtain impartial advice when faced

with proposals for financing expensive investments(e.g., major clinical trials) on which proponentsdisagree widely (e.g., HIV/AIDS vaccines, micro-bicides)?

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• Given the potential value to many actors of meth-ods to compare the potential public health benefitsof different anticipated products, and the investmentnecessary to achieve them, how best to support theirdevelopment and impartial application?

At the level of individual PD PPPsDisease/product-focus selection fundamentally deter-mines scientific challenge and the context for address-ing ‘access’. Thus, this choice influences the probabilityof success, likely necessary investment, and also po-tential public health impact. Hence at the level of indi-vidual PD PPPs the questions are:

• Does there exist a situation analysis of barriers toproduct development and access that is comprehen-sive (along the research-development-accesscontinuum) of high quality, and broadly agreed,identifying the ‘needs’ for this disease/productfocus?

• How well does the ‘niche’ adopted by the PD PPPmatch the ‘needs’ identified in the situation analy-sis?

A N N E X 4 . P U R P O S E O F T H E M E E T I N G : O P E N I N G R E M A R K S

• How realistic is the breadth and challenge of thedisease/product focus in relation to the proposedoperational of style and size. Is it likely to reach acritical mass necessary for efficient operations?

• How well do the choices regarding independent orhosted status, sector roles and collaborators, andoperational style (management oversight, portfoliodevelopment and management) recruit necessarycontributions from potential partners, includingthose from business/‘pharma’ (expertise and in-kindcontributions for product development) and thepublic sector (expedited regulatory processes, timelypublic health guidelines, efficient distribution sys-tem)?

• Does the PD PPP have a clear concept of its ‘addedvalue’ and is it measuring/reporting this, as well asthe progress of the science?

• Does it have evidence of in-kind contributions (andtheir value) to show the added value of a PPP ap-proach for its disease/product focus?

• Is there evidence of rigorous application of ‘bestpractices’ in portfolio management and accessingthe highest-quality scientific advice?

ANNEX 5

UN Millennium Development Goals

THE GOALS IMPLEMENTATION

1 Eradicate extreme ■ Reduce by half the proportion of people living on less than a dollar a daypoverty and hunger ■ Reduce by half the proportion of people who suffer from hunger

2 Achieve universal ■ Ensure that all boys and girls complete a full course of primary schoolingprimary education

3 Promote gender equality ■ Eliminate gender disparity in primary and secondary education preferably by 2005, and at all levelsand empower women by 2015

4 Reduce child mortality ■ Reduce by two thirds the mortality rate among children under five

5 Improve maternal health ■ Reduce by three quarters the maternal mortality ratio

6 Combat HIV/AIDS, malaria ■ Halt and begin to reverse the spread of HIV/AIDSand other diseases ■ Halt and begin to reverse the incidence of malaria and other major diseases

7 Ensure environmental ■ Integrate the principles of sustainable development into country policies and programmes;sustainability reverse loss of environmental resources

■ Reduce by half the proportion of people without sustainable access to safe drinking water■ Achieve significant improvement in lives of at least 100 million slum dwellers, by 2020

8 Develop a global ■ Develop further an open trading and financial system that is rule-based, predictable andpartnership for non-discriminatory. Includes a commitment to good governance, development and povertydevelopment reduction – nationally and internationally

■ Address the least developed countries’ special needs. This includes tariff- and quota-free access for theirexports; enhanced debt relief for heavily indebted poor countries; cancellation of official bilateral debt;and more generous official development assistance for countries committed to poverty reduction

■ Address the special needs of landlocked and small island developing States■ Deal comprehensively with developing countries’ debt problems through national and international

measures to make debt sustainable in the long term■ In cooperation with the developing countries, develop decent and productive work for youth■ In cooperation with pharmaceutical companies, provide access to affordable essential drugs in developing

countries■ In cooperation with the private sector, make available the benefits of new technologies – especially

information and communications technologies


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7 3

ANNEX 6

Keynote addressLinking private sector expertise in product development with

public sector goals to combat global health problemsGail H. Cassell, Ph.D. (Vice President for Scientific Affairs and Distinguished Lilly Research Scholar for

Infectious Diseases, Eli Lilly and Company, Indianapolis, IN, USA)

Statistically observed attrition rates and industrystandards for the duration of pipeline steps can be used,with estimated costs, to suggest the desired pipelinecomposition and its cost implications. An example fornew anti-malarials was presented.

The pharmaceutical industry in general however isobserving lower success rates in development of newmolecular entities (NMEs) over at least the last dec-ade. The Economist magazine had noted an overallfall in NMEs approved annually between 1991 and2003 by approximately 50% despite a two-fold rise inglobal research and development expenditures.2 Lillyitself had managed to maintain research productivitybut the situation was a challenge.

Despite the general industry desire to increase pro-ductivity, and to also see products emerge to meet theneeds of the poor, no part of the product develop-ment chain was dispensable, even in ‘public healthemergencies’. Lowering safety standards in develop-ment of certain classes of new product (such as thosefor developing countries) would be at odds with basichuman rights. The quality issue for existing productsused in many developing countries was however a causefor serious concern since a high proportion of locallymanufactured and imported products failed to meetrequired standards.

Developing drugs to confront diseases associatedwith poverty represented a challenge to all the partieswishing this to occur as no single player has the re-sources or incentives to manage the entire process. Notsurprisingly (since markets were unattractive) there wasa disconnect between development of NMEs target-ing diseases associated with poverty and the healthburdens these diseases represented worldwide. Evenamong the diseases typically associated with poverty,some (such as Trypanosomiasis, Chagas Disease, Schis-

A summary prepared by the Secretariat of theInitiative on Public-Private Partnerships for Health

In reality, bringing a new drug from concept to thepatient is exceedingly complex,1 but the multitude of

steps is necessary because of attrition among candi-dates, and the requirements of assuring safety for con-sumers.

Industry invests in iterative chemical synthesis,target selection, high throughput screening, animaltesting, pharmacokinetic analysis, toxicology and op-timization of efficacy/pharmacokinetics. It also investssignificantly in developing production and quality as-surance methods, as well as clinical studies (Phase I,II, and III), application for regulatory approval (formarketing). Post registration Phase IV studies also areoften conducted in addition to surveillance of adversereactions.

At any particular point in time a range of candidateproducts will be at various stages in the overall pipe-line for each major product class. As of the Londonmeeting antibacterials in clinical development, amongvarious companies comprised (at least) 11 candidatesin Phase I (or unknown clinical phase), seven candi-dates in Phase II, and nine candidates in Phase III. Inthe preceding two years, seven products in this cat-egory had been launched. The pattern was similar foranti-virals, however, with fewer new products launched.For anti-malarials, even including products being co-developed with one of the product development part-nerships the number of candidates was significantlyfewer. Anti-tuberculosis candidate were somewhatmore numerous, but mostly at the pre-clinical stages.

1 Nwaka S, Ridley R. 2004. Virtual drug discovery and devel-opment for neglected diseases through public-private partner-ships. Nature Reviews Drug Discovery, 2:919–928.

2 The Economist Technology Quarterly, March 2004, pp.38.



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tosomiasis, Leishmaniasis, Lymphatic filariasis, andothers) showed disproportionate impact in high mor-tality developing countries.

Development of new and improved ‘tools’ to com-bat diseases associated with poverty represented a situ-ation where collaboration was the only rationalapproach:

• Public authorities and/or philanthropic groups mayhave the resources but they lack the infrastructureto carry out the development process;

• Academic researchers may have promising biomedi-cal leads but they lack the development testing andmanufacturing expertise to bring drugs to patients;and

• Private drug companies may have the development,testing and manufacturing expertise but they lackthe necessary financial incentives where the publichealth needs of the developing world are concerned.

Many new product development partnerships wereshowing promise in product development. These in-cluded the Global Alliance for Tuberculosis in DrugDevelopment, on whose Board Dr Cassell served.Furthermore, other collaborations involving pharma-ceutical companies were underway ramping up manu-facturing capabilities, educating health care providersat the community level, providing products, ensuringtheir delivery and tracking outcomes. One collabora-tion in which Lilly itself was involved was the transferof manufacturing technology for two drugs againstmulti-drug resistant tuberculosis (MDRTB) to low-cost producers in developing countries where MDRTBwas an increasing problem.

Another approach to enabling public and privatesectors to join forces for public health purposes was toexpand the networks traditionally used to solve prob-lems. Untapped pools of talent undoubtedly existed inless well-known academic institutions contract researchlaboratories, in advanced and even the least developedcountries, in other fields related to biomedical researchand among those retired. Lilly had fostered one such

collaborative problem solving model using the Internetto reach further InnoCentive.1 Over 150 scientific chal-lenges had been posed via this system resulting in50,000 respondents from over 100 countries. Awardsto the best solution had been made in 46 cases (withfull protection of the innovators intellectual property).This novel collaborative approach to problem solvinghad been utilized by a range of problem setting com-panies in pharmaceuticals, basic and special chemicals,petrochemicals, food flavours, fragrances, agribusiness,biotechnology and consumer products.

Dr Cassell viewed the future of public-private col-laboration very optimistically:

• Public-Private Partnerships (PPPs) represent themost promising solution so far to the ‘disconnectproblem’, between resources, goals and skills neededfor development of new products to combat dis-eases associated with poverty;

• By infusing public and philanthropic money intothe process, PPPs restore some of the financial in-centives to private firms (corporate social responsi-bility should close the rest of the gap);

• PPPs also succeed by replicating the portfolio-man-agement approach to traditional drug development,and targeting it on neglected diseases;

• PPPs ‘translate’ the work of basic academic researchinto serious drug candidates, and manage thedevelopment, testing and approval process;

• The dollars of well-intentioned government anddonors will be used more effectively than in the past;

• We have learned not to neglect any part of the proc-ess – including the stages of drug development butalso the “deployment” of new therapies;

• The bottom line is that the players each know theirplaces: what they’re good at and what they’re notso good at;

• The challenge now is to figure out better ways tobring the best of the public and private sectorstogether and even enhance the current PPPs.

1 InnoCentive website: www.innocentive.com

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ANNEX 7

Questions by SessionsPeter Hall

Hierarchy for individual PD PPPs• How to identify need, define niche and conceptual-

ize portfolio?• How to operationalize and manage portfolio?• How to link upstream/midstream/downstream is-

sues?• How to determine success?• How to determine and meet financing needs?• How to determine value for money?

See Figure 1 overleaf.

Session I. The rationale for PPPs:Determining need and niche

• How and why have existing PPPs been established?• Before establishing a PPP, has there been a system-

atic analysis of: potential impact on burden of dis-ease; the public health impact on specific countriesor population groups; ongoing or planned devel-opment activities in the field; availability of exper-tise; and the potential value-added? Is this stillneeded in certain areas of activity?

• How have PPPs identified an appropriate niche?What is the product/disease focus?

• How have existing PD PPPs determined what is areasonable scope?

• Where there has been a good review of need, hasthis been adequately related to ongoing activities be-ing undertaken by others in order to identify niche?

• How has the objective of linking private sector ex-pertise to public sector goals been achieved?

• Can/should PPPs be characterized/grouped/en-couraged to communicate according to the field inwhich they are working, the types of products theyare developing or their approaches to meeting need?Do we need to consider vaccine development as fun-damentally different to drug development?

Overarching questions• Overall, are the goals and objectives of existing PD

PPPs based on meeting major public health needsand achieving access to products for the poor in de-veloping countries? Are all major needs covered?

• How did founders and/or funders of particular PPPsdetermine the ‘need’ and the PD PPP’s ‘niche’ toaddress that need? (Was there a broad consensusdevelopment process to get wide buy-in?)

• Are there overlapping PPP missions? Is this healthycompetition or wasteful duplication?

• Are there public health needs that are not beingaddressed?

• Could/should a more systematic approach to iden-tifying and addressing ‘needs’ (for improved diseasecontrol tools) be developed? If so, who should drivethis process?

• Can a common terminology be developed to de-scribe the strategic, operational and financial mod-els of different PPPs?

• Can a methodology be developed to allow compari-son of strategic approaches, operational mechanisms,financial needs and ability to meet public healthneeds between PPPs?

• If the ultimate goal of product development is pub-lic health benefit, how well are different PPPs do-ing in quantitatively estimating their likely publichealth impact (as opposed to the burden of diseasethey address)?

• What are the funding requirements to ensure thatappropriate products for neglected diseases are de-veloped and become accessible at an affordable costto those that require them? How can we improvethese estimates?

A N N E X 7 . Q U E S T I O N S B Y S E S S I O N S


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Figure 1. Successfully meeting needs

Success

Identifying and addressing downstream issues in a timely manner

Maintaining a quality portfolio(best possible review;

optimal timelines;most appropriate partners;

ensuring funding;ability to discontinue product)

Developing a ‘quality’ portfolio

Meet need

Funders

Review bodies

Identify needs

Need

Define niche andconceptualize portfolio

Operationalize andmanage portfolio

Addressdownstream

issues

Undertakediscovery, preclinical,

phase I, II, IIIstudies

Session II. Determining and managing the portfolio• Have existing PPPs articulated well defined prod-

uct profiles/characteristics that they are workingtowards?

• How do PPPs select products within their portfo-lio, particularly those at different stages of develop-ment? Are they the best possible scientific leads? Didexisting PPPs begin with an assessment of the fieldto allow conceptualization of a portfolio or did theystart with those candidate products that were avail-able to them?

• Does the PPP have access to, or ability to leverage,the best platforms, knowledge and expertise? Whatare the obstacles to accessing the most promisingprospects?

• Does the PPP have sufficient financial resources tofulfil its determined niche?

• Do the PPPs feel that there is a critical mass of in-house staff necessary for efficient operations and, ifso, what is it?

• How does a PPP define priorities and relative budgetallocations within its portfolio?

• To what extent is this influenced by the PPP’s part-ners/funders?

• How does a PPP determine the quality of its port-folio? Is this done by evaluating product leads withinthe portfolio or by evaluation of the field?

• Do they know what fraction of all promising candi-dates are in their portfolio?

• What is the governance structure of the PPP?• Is there a clear business plan? Are the defined goals

achievable?• How are partners identified? If a good scientific pro-

posal is developed how does the PPP ensure thatthere are appropriate partners? Does the proposalspecify what inputs are expected from each partner?Are roles and responsibilities clearly defined? Arethere tensions between public and private sectorpartners?

• Have PPPs developed via a planned partnershipbased on defined roles and expertise needs or bycontracting for services with the private sector asrequired?

• How do PPPs manage their project activities?• To what extent are private sector business practices

used?• Is there a difference in management between PPPs

that are independent entities and those that arehosted by other public sector bodies?

• How does the PPP balance operational quality withpositioning for their own visibility?

• Is advocacy needed in the PPPs’ field of operation?If so, with whom and at what stage?

• What financial management mechanisms have been

7 7

instituted? Does the Board have an audit commit-tee?

• Are the management, operational and financialmechanisms of PPPs transparent?

• Do existing PPPs fully use their staff and partnerresource capacity/capability? Is there scope for shar-ing resources between PPPs in the same field orthose facing similar downstream issues?

• How do PPPs define and monitor success? Haveunequivocal, scientifically based milestones been es-tablished at the outset within realistic timelines?

• Is success determined solely by achieving milestonesin the development of a specific product or also byreviewing the status of similar products being de-veloped by others? Has it stimulated others to workin this area or are there better products now underdevelopment? Does a portfolio approach make iteasier to discontinue specific products?

• What review procedures have been established? Arethe PPP’s activities reviewed in-house or by a panelof independent experts? If the latter, how frequentlydo they meet and what is their remit? Does the re-view committee include private sector expertise? Dodonors serve on review bodies?

• When and how is the balance of activities determinedand assessed? Are there rigorous and robust mecha-nisms to maintain a balanced portfolio? Have crite-ria been developed to assist in determining whendevelopment of a product should be stopped? Is thePPP willing to stop product development if signifi-cant difficulties have arisen or better products arelikely to be available from others in a similar timeframe?

• Is there a difference in review mechanisms betweenPPPs that control everything in-house and those thatwork through a group of partners?

Session III. Planning from discovery research tointroduction

Upstream• Are sufficient promising candidate products avail-

able for the PD PPP to create a meaningful port-folio? If this is a limitation, how serious a problemis it? What does the PPP currently do to overcomethe problem?

• Does the PPP have routine contacts with the basicresearch community related to its disease? How?

• Does the PPP currently play a role in fostering veryearly research on possible product concepts/candi-dates? How could it be helped to achieve better ac-cess to early product concepts by links with bothacademic and pharma partners?

• Is there a need to strengthen R&D capacity in de-veloping countries so the PPP has more partners indisease-endemic countries (DECs)? Is this currentlyregarded as a PPP responsibility?

• Do PPPs consider that they are developing prod-ucts for the poor in developing country environ-ments or do they start by considering the scienceand assume that the downstream issues (includingsuitability for DEC use) can be resolved later?

• Are developing country stakeholders involved fromthe outset? (Everybody will say, “Yes”, but the ques-tion should also be asked: “Is research capacitystrengthening one of your primary goals or is it apotentially useful by-product to the way you work?”)

• How do PD PPPs currently handle proposals thatare too early for them to fund or involve unprovenapproaches?

Midstream• What role does the PPP plan (or need) to take in

clinical trial capacity strengthening, including de-veloping ethical review bodies and ensuring GCPin trial implementation?

• What collaboration is possible between PPPs tomaximize use of clinical trial sites or other develop-ment expertise?

• Who should fund and take the lead in strengthen-ing:— ethical review capacity?— clinical trials capacity (to pivotal licensing stand-

ards)?• Do any mechanisms currently exist to coordinate

funder support for these capacity strengthening ef-forts? If not, who could take the lead in developingmore coordination?

• Are public sector partners adequately engaged – atthis stage – to expedite:— ethical review for trials initiation?— regulatory approval?— demand estimation?— policy formulation?— uptake?

A N N E X 7 . Q U E S T I O N S B Y S E S S I O N S


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Downstream• Do PPPs evaluate downstream requirements, e.g.,

manufacturing capability, product stability and stor-age requirements, product cost, product registra-tion, demand creation, donor/governmentpurchase, health system service delivery capabilities,etc.? If so, how?

• Do PPPs include these downstream requirementsin their business plans? If not, why not?

• As phase III trials begin, are parallel activities plannedand budgeted for demand creation, financing andintroduction? Do they begin to address service de-livery mechanisms where they either do not exist ordo not function adequately for the type of productunder development?

• Has the PPP identified downstream stakeholders aspartners or members of review bodies? If so, at whatstage are they involved?

• How does the PPP address final product cost andtransfer of technology? Where a PPP is built on in-ventions from a patent holder (for example, a smallbio-pharma company), how are agreements madewith the IP holder on final product cost or the rightto seek other producers?

• What collaboration could/should be expected acrossPPPs to achieve downstream goals? Could any col-laborative mechanisms be considered?

• How do PPPs handle the situation where (publicsector) delivery systems are not functioning well andhence likely to reduce the public health benefit ofits outputs?

Session IV. Financing the PPP• What has the financial contribution of the private

sector to the PPPs’ activities been? Can in-kind sup-port be quantified?

• Does the PPP receive unearmarked funding? Hasdemonstration of good performance been the prin-cipal reason for continuation of such funding or hasit been aided by having a portfolio of products?

• Does the PPP have one or multiple donors? If mul-tiple, do the donors have different funding condi-tions and/or expectations?

• Was initial funding based on a single product or onthe development of a portfolio?

• What funding assumptions have been made in thebusiness plan? Are the financial projections adequateto achieve end goals? How far has the PPP succeededin meeting those projections, in terms of actual orpledged funding?

• Do multiple donors have different funding cycles/conditions? If so, how are these reconciled?

• Since most PPPs have different financing needs orapproaches to their needs, is there a way to achieve‘equivalence across PPPs’ for comparative review?How can estimated budgets for products at differ-ent stages of development be compared?

• How are financial needs linked to the perceived roleof the PPP?

• How do different operational models affect actual/perceived financial needs?

Value for money and related donor issues• To what extent do bilateral funders consider that

PPPs ‘misdirect’ funds to the commercial/privatesector?

• How do funders know that they are getting valuefor money? Do they have access to the outcomes ofthe PPPs’ review process as well as independentevaluations from the field? How do donors deter-mine their risk profiles? How do they know theircontribution is making a difference?

• Do funders include downstream issues in their‘value’ reviews?

• Even if it is acknowledged to be important to investin a given field, how does the funder know that itscontribution will make a difference?

• Do funders attempt to link funding to an identifiedlead that is likely to achieve its objective or will theyprovide unearmarked funding?

• Is there an optimal mechanism for funders to makeinvestments in order to achieve best value?

• Can funders be realistically expected to provide thenecessary funding to all ongoing PPPs or is there aneed for some form of systematic review across andwithin fields of activity? If so, who could/shoulddo this?

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ANNEX 8

Background papers’ key messages(by sessions)

SESSION II

Portfolio management in pharmaceuticalcompanies and PD PPPs

Portfolio management in thepharmaceutical industry(Esther Schmid, Pfizer, UK)• R&D is inherently risky and therefore many simul-

taneous discovery efforts are needed if a medicine isto be produced.

• Key performance indicators are used to build andactively manage a portfolio so that it has a highchance of success.

• Portfolio management limits risk, time to marketand costs.

The emerging landscape of public-privatepartnerships for product development(Alison Sander, Consultant, USA and Roy Widdus, IPPPH,Switzerland)• Portfolio management is critical because product

development is such a risky and lengthy process.Estimates of the time and cost required to developa drug in the private sector range from US$400–650 million and 8 to 15 years.

• Portfolio management has two components –diversification (reduced reliance on a small numberof candidates with similar characteristics) and ro-bust portfolio management processes (to ensure thatcandidates which do not meet the desired specifica-tions are actively weeded out).

• A key issue with neglected diseases is the level andperspective from which portfolio analysis is applied.One could view all 25 PD PPPs developing prod-ucts for neglected diseases as a single portfolio. Port-

SESSION I

Opening of the workshopRoy WiddusInitiative on Public-Private Partnerships for HealthGeneva, Switzerland

The workshop is a unique opportunity to considercollectively three important topics:

• How can we most usefully define and conceptual-ize the ‘field’ of improving tools for control of ne-glected diseases?— If the ultimate objective is public health impact,

‘access’ issues will need to be addressed; the PDPPPs may have to encourage action on theseissues if no one else is doing so adequately.

— How do we estimate future potential publichealth benefit?

• How can we improve communication and under-standing among implementers and funders?— Especially across the PD PPPs and along the

research-development-access continuum.• How can we make future decisions based on better

information?— Need to identify what to monitor and analyse

further.

The issues related to these three questions can begrouped as those that relate to the broader field, andthose that relate to the individual product develop-ment partnership.

It is perhaps more important to decide how to con-tinue the information exchange and analysis than tobelieve that all questions can be decided at this meet-ing.

A N N E X 8 . B A C K G R O U N D P A P E R S ’ K E Y M E S S A G E S


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folio management is also a tool that can be appliedto the product portfolios of individual PD PPPs.The key issue is what is being optimized.

Demonstrating value: Performance metricsfor health product development publicprivate partnerships(Mark Pfitzer, Foundation Strategy Group, Switzerland)• Comprehensive performance metrics go beyond

funds raised and disbursed, and demonstrate howprogress on value-added activities impacts R&D andoperational costs.

• PD PPPs exploit their legitimacy and knowledge,and reach advantages to create value in four waysby:— Building unique capabilities and platforms to at-

tract and select the most promising projects— Improving their partners’ research capabilities— Mobilizing funds in line with portfolio and or-

ganizational developments— Enhancing knowledge and knowledge dissemi-

nation among research partners and the broaderpublic health actors involved in turning newproducts into health impact.

• Performance dashboards metrics that highlight aPPP’s primary added-value activities will both en-courage donors and focus the PPPs on the activitiesthat will most contribute to their success.

SESSION III

The role of PD PPPs and the environmentnecessary for their success

The current research-to-development ‘hand-off’process for product concepts/candidate productsand possible improvements in it(Solomon Nwaka, MMV, and Roy Widdus, IPPPH,Switzerland)• Investment in basic research will only benefit pa-

tients if it is efficiently translated into early candi-date products; however, this process is currentlysub-optimal.

• Various approaches to improving this ‘translation’have been identified.

• New funding mechanisms, aimed at public, or pub-lic interest, institutions are warranted as part of a

comprehensive approach to improving tools to com-bat neglected diseases.

The emerging landscape of public-privatepartnerships for product development(Alison Sander, Consultant, USA and Roy Widdus, IPPPH,Switzerland)• While each PD PPP has a unique mission and set of

challenges, strategic and operational choices caninfluence both the cost to achieve a mission and thelikelihood of success. Our paper looks at a range of16 variables and extracts the factors that are thoughtmost likely to be critical for success.

• At the level of individual PD PPPs, success willprobably be a function of strategic fit between eightvariables:— the challenge identified— the readiness/complexity of the science— the willingness of donors to support the venture— the match with downstream needs— the quality of management— the robustness of the portfolio— the level of independent oversight— the quality of strategic partnering.

• In addition to these eight factors, it is importantthat each PD PPP manage the following three ele-ments :— Finding the right balance between a concern

about upstream science and downstream accessissues

— Managing the multiple interface points wherehand-offs are expected or where different con-tractors are involved

— Developing intellectual property and contractagreements that balance in the long term withthe flexibility required during the developmentphase.

• The ability to attract other sources of funding overthe long term will also depend on the view of theoverall PD PPP field. It is important that donorsand PD PPPs develop projections of the funds re-quired for product development, define interimmetrics of progress, work to attract other donors tothe field, and look for places where sharing plat-forms may bring efficiencies to the field.

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Ethical review capacity: Country needs, role andresponsibility of partners and researchers(Rose Leke, University of Yaoundé, Cameroon)• Ethics review committees: Weak, ineffective, inad-

equate training, no access to international guide-lines – interpretation, lack of standard operatingprocedures (SOPs).

• Informed consent – western perspective: Individual/personal rights in Africa: family, community. Trueinformed consent often questionable.

• Collaboration – partnerships— Collaborator-donor, who owns research— Rights of ‘receiver’: financial, publication, prop-

erty rights— Overheads blind the review process— Accountability.

• Advocate for sound ethical review practices in Africa.

What else needs to be in place for PD PPPs to dotheir tasks effectively: Clinical trials capacity(Ebi Kimanani, International Biomedical Research in Africa[IBRIA], Kenya)• Pipeline: Globally, there are over 300 products in

development for HIV, 45 for malaria and 22 fortuberculosis.

• Current capacity: A gap exists between the clinicaltesting capacity required to support this pipeline andwhat is available in sub-Saharan Africa.

• Way forward: Funding, scientific and regulatoryleadership are needed to build infrastructure, hu-man resources and essential systems to meet thisdemand.

Emerging lessons in preparing for uptake of newvaccines(Gargee Ghosh, Center for Global Development, USA)• Achieving health impact requires not only product

development but successful product introductionand widespread, sustainable uptake

• Successful product introduction requires planningthat starts while the product is in the developmentpipeline – PPPs need to start thinking about thistoday to avoid wasting precious time later

• Planning for introduction requires not only explicitfocus but also a new set of skills, analyses and ap-proaches that the global community will need todevelop.

The current research-to-development ‘hand-off’process for product concept/candidate products andpossible improvements in it(Solomon Nwaka, MMV, and Roy Widdus, IPPPH,Switzerland)More public sector attention needs to be paid to mecha-nisms and resources to assist in the translation ofscientific innovation into practical, product-directeddiscovery and development. Ideally public-private part-nership is also required for this upstream activity wherewe need to build capacity, with equal attention to pro-viding opportunities in developing as well as developedcountries

• Further evidence will be required downstream ofproduct registration to justify public sector purchaseof products and their incorporation into essentialdrug lists, national policies and guidelines. Prepara-tion for such studies will be required during the laterstages of product development and the transitionneeds to be carefully managed

• The overall process should be seen as one of pro-viding evidence to make public policy decisions, notof ‘promoting’ one product over another. The proc-ess of evidence generation needs to ensure an ap-propriate level of data ownership at the country leveland utilize and develop research capacities.

SESSION IV

Financial aspects of product development forneglected diseases

What is the current financial situation for PD PPPsusing the portfolio management approach?(Adrian Towse, Office of Health Economics, UK)• Responsibilities: A key question is whether portfo-

lio management responsibilities should lie with thedonor or with the PD PPPs

• Performance: It is difficult for donors to assess per-formance when some PD PPPs do not have quanti-fiable objectives

• Supply constraints: Portfolios need to be largeenough to deal with failure, but only take projectsjustified by scientific merit

• Cost estimates: Differences in cost estimates for clini-cal phases highlight the need for greater transpar-ency in PD PPPs projections



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• Capacity building: The need to estimate infrastruc-ture investment for conducting clinical trials is key

• The financing gap is large between the funding avail-able to PD PPPs and the finances needed to getproducts to market.

The costs of developing vaccines: Case study ofVaxGen’s candidate HIV vaccine(Donald P. Francis, Brisbane, CA, USA)• With the current for-profit paradigm of pharmaceu-

tical development, the power of modern science willnot be harnessed to prevent disease

• AIDSVAX, VaxGen’s candidate HIV vaccine, hasrequired over 20 years of development and cost ap-proximately US$200 million, but is far from com-plete

• The problem is not the lack of scientific/technicaltools available for vaccine development but ratherthe will to finance and use them

The cost of trials and manufacturing processdevelopment for vaccines(Jerry Sadoff, Aeras Global TB Vaccine Foundation, USA)• Field sites require building good clinical practice

infrastructure and availability of enough valuablecases of the disease being studied

• The best way to satisfy both these requirements isto perform longitudinal cohort studies in targetpopulations that are similar to vaccine studies interms of enrolment, follow-up, monitoring and datamanagement

• Accurate estimates of vaccine uptake curves basedon product profiles and projected prices are requiredfive years before vaccine licensure to ensure capitalinvestment in properly sized factories so as to pre-vent tragic delays in vaccine availability.

PD PPPs for diseases of poverty: Are there moreefficient alternatives? Are there limitations?(Robert G. Ridley, WHO/TDR, Switzerland)• Completely private sector and completely public

sector models exist for product development of dis-eases of poverty, but history indicates that, so far,PPPs have delivered new tools more effectively forthese diseases and at a relatively low cost. Synergiesof infrastructure and human expertise account forthis enhanced cost-efficiency

• Despite increased funding for diseases of poverty,resources are still extremely low, and activities arefragmented compared to the huge ‘economies ofscale’ of major pharmaceutical companies. The com-munity needs to ensure better agreement on targetproduct profiles and better coordination of effortwithout creating ‘monopolies’ whereby one groupeffectively controls all R&D activity

• The building of essential research, organizationaland managerial capacities, particularly in the devel-oping countries, is essential to the long-term, sus-tainable generation of relevant new and innovativeproducts to address diseases of poverty. Researchcapacity building and broad ‘stakeholdership’ involv-ing developing countries should be integral to ouractivities, and not just perceived as ‘nice to have’.

SESSION V

Possible innovative approaches to funding productdevelopment for neglected health problems

PPPs and product development: Innovativefinancing opportunities and the need for a ‘businesscase’ approach(Amy Batson, World Bank, USA; Raj Shah, Bill & MelindaGates Foundation, USA; Chris Gingerich, Consultant, Bill &Melinda Gates Foundation, USA; and J. Niels Rosenquist,Consultant, World Bank and GAVI)• Capital markets may provide access to new sources

of investor money, and may provide other tools tooptimize existing financial flows

• The ability to attract investor money is based onthe presumption of a guaranteed future market forthe product in question

• PD funding is not generally a priority for traditionalsources of major development financing

• There are, however, emerging opportunities amongnew multilateral funds and new programmes inmajor development financing institutions

• Business case-style analyses and funding proposalsfocus on communicating return on investment (fi-nancial and/or programmatic) to potential funders

• As PPPs become more competent at business case-style analyses, they will be better positioned to ob-tain financing from any source.

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Do guarantee purchase mechanisms serve as anincentive for product development?(Gargee Ghosh, Center for Global Development, USA)• Guarantee purchase mechanisms can be designed

to provide market assurances that help mitigate someof the critical risks inhibiting product developmenttoday

• The work of the Pull Mechanisms Working Groupshows that these mechanisms are legally and practi-cally feasible, and would have an effect on somefirms’ investment decisions

• These mechanisms need to be part of a comprehen-sive product development strategy – they are not(and should not be used as) a ‘silver-bullet solu-tion’.


ANNEX 9A

Estimates of the medium-term financial resource needsfor development of pharmaceuticals to combat

‘neglected diseases’Adrian Towse, Jorge Mestre-Ferrandiz, and Olwen Renowden (Office of Health Economics, UK)

funding available to PD PPPs and the finances theyare likely to need to get products to market. Donorsand PD PPPs need to improve their understanding ofthe likely size of the gap and how it might be filled.

We used three approaches to arrive at estimates ofthis gap:

1. Using PD PPP estimates of the cumulative fundingpledges they have received and a mix of sources forestimates of their cumulative resource requirements,we found that for four PD PPPs (TB Alliance,DNDi, MMV, IAVI) the gap is around US$1.2 bil-lion.

2. Calculating the development costs of existing PDPPP portfolios we estimated a shortfall of US$720mfor vaccines and US$730m for drugs, making atotal of US$1,450m. It should be borne in mind,however, that the PD PPPs are still building theirportfolios and the number could be higher;

3. Our third rule of thumb was to assume that each ofthe 14 PD PPPs included in our analysis broughtone product to market at an average out-of-pocketcost of US$160m (roughly in the middle of theUS$128m–192m range we found). This would in-volve costs of US$2.2 billion.

Using these three approaches we estimated the fund-ing gap at between US$1.2 billion for four PD PPPsto US$2.2bn for 14 products, depending on theassumptions made, which include:

• which PD PPPs are included;• size of portfolio;• attrition rates and costs; and• any offsetting contributions in-kind.

Executive summary

This paper has been prepared for a workshop organ-ized by the IPPPH on 15–16 April 2004. The focus

of the brief is to analyse the financing needs of a numberof portfolio-based PD PPPs. In particular we were askedto inform donors of the potential funding gap whichPD PPPs might face over the medium term if they areto achieve their stated product development objectives.

If donors are to achieve new licensed drugs andvaccines for neglected diseases, then they have to dealwith the low likely success rates of individual projects.The best way to do this is through a portfolio of in-vestments. The PD PPPs are better placed to managea portfolio of projects than individual donors. Thequestion then arises as to how much money the PDPPPs need to achieve their objectives in managing theseproject portfolios on behalf of donors.

The PD PPP estimates of discovery and develop-ment costs and project attrition rates show major dif-ferences in both the discovery/pre-clinical and theclinical phases. It is not clear why there is such varia-tion and there would be benefit in some shared under-standing between donors and PD PPPs as to the basisof project cost projections across different PD PPPs.In particular we note that:

• Statistical data on failure and attrition rates are verypoor for vaccines;

• Two important areas of cost need more examina-tion – manufacturing costs and investment in clini-cal trial infrastructure;

• There is a need for a much better understanding ofthe potential value of in-kind benefits from indus-try and others.

In spite of the difficulties of estimating potential costsit is clear to us that there is a large gap between the


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IntroductionContextThe product development public private partnerships(PD PPPs) were set up to help address a market failure– the lack of commercial incentive to undertake R&Dinto drugs, vaccines and diagnostics for diseases ofpoverty. The problem of failure is easiest to highlightin the cases of drugs and vaccines. Discovery and de-velopment costs run into hundreds of millions of USdollars. Yet patients in less developed countries andtheir governments do not have the money to pay pricesthat will enable these R&D costs to be recovered.

Donor money – public, philanthropic or fromnongovernmental organizations (NGOs) – is thereforeneeded to fund R&D into these diseases and/or toprovide incentives for the private sector to undertakethis work. Expertise in drug and vaccine developmentlies with industry. Hence the attraction of forming PDPPPs as not-for-profit bodies standing between thepublic and private sectors but including both asstakeholders, seeking to work with industry to developproducts to tackle key global health problems (Widduset al., 2001).

There are other mechanisms to provide incentivesto the private sector pharmaceutical industry, usuallycategorized into ‘push’ (reducing industry coststhrough grants, tax breaks, fast track approvals) and“pull” (creating effective demand, for example via glo-bal funds1 and advance price and purchase commit-ments). These are not mutually exclusive – most PPPsplan to license products to the private sector wherethere is sufficient commercial incentive for them to doso. Understanding the potential role of other ‘push’and ‘pull’ measures to involve the private sector is cru-cial to understanding future PD PPP financing require-ments (as we discuss later) and to improving theviability of PD PPPs as a mechanism to deliver newproducts (Kettler and Towse, 2002).

Because of the emphasis on product developmentand the high risks of failure associated with bringingproducts through the R&D process, most PD PPPsproceed with a number of projects, depending on theresources they have and the potential scientific valueof the projects. This implicit or explicit portfolio ap-proach is another important way in which PD PPPs

differ from many of the other projects and organiza-tions that donors fund. We return to this issue below.

Objectives/terms of referenceThis paper has been prepared for a workshop organ-ized by the IPPPH on 15–16 April 2004. The focus ofthe brief is to analyse the financing needs of a numberof portfolio-based PD PPPs. In particular we were askedto inform donors of the potential funding gap whichPD PPPs might face over the medium term if they areto achieve their stated product development objectives.The list of PD PPPs is in Table 1 below. The key ele-ments are to:

• outline the product development objectives of thePD PPPs. What is the PD PPP saying it wants to

Table 1. The IPPPH list of PPPs

Focus of financial analysis

DNDi Drugs for Neglected Diseases initiative

MMV Medicines for Malaria Venture

IAVI International AIDS Vaccine Initiative

TB Alliance Global Alliance for TB Drug Development/TB Alliance

Other portfolio based PD PPPs

Aeras Global TB Vaccine Foundation

IOWH Institute for OneWorld Health

MVI Malaria Vaccine Initiative

FIND Foundation for Innovative New Diagnostics

SAAVI South African AIDS Vaccine Initiative

EMVI European Malaria Vaccine Initiative

HHVI Human Hookworm Vaccine Initiative

IPM International Partnership for Microbicides

MDP Microbicide Development Programme

PDVI Pediatric Dengue Vaccine Initiative

PPPs not included in the study remit

Pneumo-ADIP Pneumococcal Vaccine Accelerated Development andIntroduction Plan

Rota-ADIP Rotavirus Vaccine Accelerated Development andIntroduction Plan

BVGH BIO Ventures for Global Health1 For example, GAVI / Vaccine Fund and GFATM.

A N N E X 9 A . E S T I M A T E S O F T H E M E D I U M - T E R M F I N A N C I A L R E S O U R C E N E E D S

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achieve and in what time frame (e.g. bring a vaccineto market by 2010)?

• identify the resources the PD PPP calculates it needsto deliver these objectives, including the assump-tions made about the contributions of others (e.g.,is there an assumption that industry or a govern-ment body such as USAID or the EDCTP will funda phase III trial?);

• analyse whether we think this calculation is reason-able to deliver those objectives, and if not how muchwill be required;

• set out the resources currently committed by do-nors to the PD PPPs; and

• conclude as to the potential ‘funding gap’ that do-nors may have to fund if the PD PPPs are to achievetheir product development objectives.

In the event, lack of data and time constraints haverestricted our ability to deliver these terms of refer-ence. Data problems encountered include distinguish-ing between product development costs and the costsof other PD PPP activities; relatively short-term finan-cial projections given the length of time it takes to bringa drug or vaccine through the development process;the relatively immature state of the project/productportfolios in a number of cases (most PD PPPs appearto have no portfolio projections and only two – MMVand DNDi – have an explicit model of portfolios withexpected success rates); and a lack of detail about as-sumptions made of expected in-kind or funding con-tributions from industry partners or other agencies.We must make it clear that this does not necessarilyreflect a lack of responsiveness on the part of the PDPPPs. They are, for the most part, simply not currentlygeared up to make long-term funding projections basedon a portfolio approach to achieving their productdevelopment objectives.

After discussion with IPPPH we revised our objec-tives in the light of the material available. The key as-pect of our work is to help donors understand how toassess whether the PD PPPs have the financial resourcesto build portfolios of projects that will enable them todeliver their objectives.1 We have therefore:

• focused on a subgroup of four PD PPPs for the fi-nancial analysis – MMV, IAVI, TB Alliance and

DNDi. Where possible, the portfolio expectationsand financial needs of the remaining PD PPPs arediscussed;

• analysed why portfolios are important for donorsand PD PPPs; and

• made recommendations to identify the issues do-nors may wish to address in respect of informationneeds for future decision-making to enable them toappraise progress and understand potential futurefunding requirements.

Method of workingIn researching this paper we undertook:

• in-person interviews (with IPPPH, MMV, MVI andEDCTP) and telephone interviews (with MMV,DNDi, TB Alliance and SAAVI);

• a questionnaire survey (with responses from MMV,MVI, DNDi, TB Alliance and SAAVI);

• use of IPPPH to collect information on PD PPPobjectives, finances and project/product portfolios.IPPPH surveyed the PD PPPs on our behalf;

• literature searches on drug and vaccine developmentcosts. We were also given drafts of relevant studiesprepared for the IPPPH workshop; and

• a review of earlier work we had undertaken lookingat drug and vaccine development costs for PD PPPs.

The information gathered by IPPPH was key and weused their summary table as the basis of further inves-tigations about the ‘current’ versus ‘desired’ portfo-lios of the PD PPPs. In telephone interviews, we askedthe PPPs to verify the portfolio content data collatedby IPPPH and we also solicited feedback on a numberof other issues including the extent to which differentactivities would be funded using their own resourcesas compared to those of other parties, and funding gapsfor product development through to 2007.

The relevance of a portfolio approachWhy a portfolio approach?The PD PPPs have been characterized as requiring aportfolio of projects because of the high attrition ratesin developing both drugs and vaccines. If the objec-tive is to get products licensed, then enough projectsneed to be in the pipeline to compensate for failures.

If some risk is to be diversified, however, the projectsthat make up the portfolio need to be sufficiently dif-

1 We are not in a position to comment on the scientific value ofportfolios or projects.

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ferent from one another in order that the probabilityof the portfolio delivering is greater than that of anyone of its component projects. Portfolio managementalso raises important issues about the relationship be-tween the donors and the PD PPPs and about the effi-ciency of managing a portfolio.

Diversifying riskThe greater the similarity between two projects (in sci-entific approach, for example), the more likely it is thatthey will either both succeed or both fail. The key toreducing risk is to combine projects that have differ-ent underlying characteristics. A distinction is usuallymade in the financial literature between systematic andunsystematic risk.1 Systematic risk is the element of riskthat is shared across projects and cannot be diversi-fied. In the context of PD PPPs this might include:

• the disease area the PD PPP is tackling: it may be aninherently difficult or less difficult area scientifically;

• the technology (drug or vaccine): this may also beinherently more or less challenging;

• scientific approaches taken in particular projects(e.g., choice of target);2

• management skills, including the ability to choosepartners and subcontractors and to progress or ter-minate projects. These will affect the ability of theorganization to deliver successfully.

Thus a PD PPP could diversify risk by working on morethan one technology and/or in more than one diseasearea. However, it may not be efficient for it to do so(see ‘Are there management efficiency gains?’ below).More importantly it is fundamental to understand thatthe real problem of managing risk is at the donor level.If the donor’s objective is to tackle HIV/AIDS,malaria and tuberculosis (TB) and other diseases ofpoverty, then it is not possible for the donor to achievethat by diversifying into other disease areas.3 The issuethen becomes one for the donor as to whether to fundone or more organizations to tackle each of thesediseases and whether to fund individual projects or aportfolio.

Implications for the relationship between the donorsand the PD PPPsWhether or not a PD PPP has a portfolio approach hassignificant implications for the relationship between the

PD PPP and its donors.4 The problem for the donorsis how to ensure that the PD PPPs – as the donors’agents – are doing the best job they can with the re-sources they have. If the PD PPPs have a portfolioapproach then it is possible for the donors to adopt amore ‘arm’s-length’ approach and look at whether thePD PPP is delivering the final outputs from the pipe-line in terms of licensed drugs/vaccines. It does notneed to get involved in the detail of how individualprojects are progressing within the portfolio, althoughit will want to be satisfied that effective management isin place and that there are processes to ensure the sci-entific quality of the portfolio. The analogy is with alarge investor in a major pharmaceutical company.However, some donors may be used to minimizingthe discretion they provide to recipients because theydo not have confidence in their judgement. For them,the portfolio approach may require a change in atti-tude.

If, however, the PD PPP does not have a portfoliogeared to achieve a specific flow of final outputs buthas a much smaller number of projects, it is harder fordonors to assess performance. In this case the analogyis with a venture capital investor. There is a high riskthat all of the projects will fail, but this does not neces-sarily mean that the PD PPP has chosen poorly ormanaged its projects badly. It does mean that the do-nor will have to manage its funding more actively. Thisis for two reasons:

• It is harder for the donor to understand whetherproject selection and management are working.

• There is a problem of asymmetric information: thePD PPP is much better informed than the donor

1 In financial portfolio management the objective is to reducethe expected variability of financial returns relative to the ex-pected mean return by diversifying unsystematic risk.

2 Strictly what matters is the covariance of returns. A PD PPPcould pick two alternative approaches whose success was mu-tually exclusive, i.e. they relied on opposite assumptions aboutthe causes or treatment of the disease. If one worked, the othercould not and vice versa. Choosing to undertake both of theseprojects would reduce risk. Of course both might still fail be-cause, for example, neither analysis of disease pathways wasaccurate.

3 They could, in principle, diversify into other ways of tacklingthese diseases. Presumably, however, prior analysis suggestedthat funding R&D was a cost-effective way of achieving valu-able global health gain.

4 The branch of economic theory that analyses relationships ofthis type is called principal–agent theory.



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about the likely prospects of the project. If it hasvery few other projects then it may be tempted topresent a more optimistic view of a project’s ulti-mate likely success than the underlying science andresults to date suggest.

Typically venture capital organizations overcome theseproblems through staged payments linked to successcriteria that can be independently verified. However,they also usually employ highly skilled staff to managetheir investments.

Are there management efficiency gains?Are disease- and/or technology-specific portfolios thebest way to proceed? It is probable that scientific ex-pertise has a strong disease- and/or technology-spe-cific element to it. Thus there are likely to be gains inefficiency from specialization. Most PD PPPs do spe-cialize in either drugs or vaccines or diagnostics, andare disease specific. Only DNDi and IOWH cover sev-eral disease areas. DNDi focuses not only onkinetoplastoid diseases (Chagas disease, leishmaniasisand sleeping sickness) where there are scientific links –but also on malaria. IOWH is also involved in thesediseases – plus diarrhoeal disease and intestinal worms.

There may also be spillover effects, i.e. benefits fromundertaking more than one research project within asingle organization. Studies (e.g. Henderson andCockburn, 1996) suggest that research can be moreproductive in total when projects are within one or-ganization than when they are split across organiza-tions.

Do PD PPPs need to have portfolios?It is important to understand that if the donors wantto achieve certain objectives (such as new, licenseddrugs/vaccines for neglected diseases) then they haveto deal with the probability of individual projects’ lowsuccess rates. They need to manage their risk relativeto the expected gains from successfully tackling theseglobal health problems. The best way to do this isthrough a portfolio of investments. The question iswhether the portfolio approach rests with the donoror with the PD PPPs. Arguably the PD PPPs are bet-ter placed to manage a portfolio of projects. Donors,with one or two exceptions, do not have the resourcesto manage individual projects or to deal appropriately

with high failure rates. Their culture may also not beappropriate. Project failures may tend to be misinter-preted as organizational failures and less than optimalfunding put in place as a result.1

Do the PD PPPs have portfolio approaches?Table 2 sets out the productivity objectives of the PDPPPs, while Table 3 summarizes their current portfo-lios in terms of the numbers of projects at each stageof development. In total there are 79 projects at vari-ous stages of development. It is clear that most of thePD PPPs have portfolios of projects and objectives thatrequire a portfolio approach. However, we would makethe following points:

• Some PD PPPs do not have quantifiable objectives.This will make it harder for donors to assess per-formance.

• Not all PD PPPs have had the time or resources toestablish a portfolio that will enable them to meettheir objectives.

• There is no point in establishing quantifiable objec-tives that are out of line with the funding requiredto achieve them. In particular, if the portfolio is toosmall relative to the objective because of a lack offunding, there will be pressure on the PD PPP tokeep unpromising projects going in the hope ofachieving their objectives. Having a portfolio thatis large enough to deal with project failure is cru-cial.

• Conversely there is no point in pushing PD PPPs tohold a portfolio that is larger than justified by thescientific merit of the projects available. This willsimply result in larger failure rates later in the devel-opment process.

Overall we conclude that portfolio approaches shouldbe used at the PD PPP level and that donors shouldseek to align funding with objectives; for example, if alarge portfolio is not realizable then quantifiable ob-jectives should be adjusted downwards accordingly.

1 For example, project failure in a portfolio management con-text may lead to resources being switched over to back theremaining projects. In a non-portfolio management organiza-tion, project failure may be taken as a sign that the whole areaor the organization is high risk and so lead to disinvestment.

8 9

Table 2. PD PPP productivity objectives

PPP Productivity goal (preferably quantitative)

Aeras One TB vaccine within 10 years

DNDi Six to seven new registered drugs by 2015

EMVI To bridge the conceptual and operational gapsbetween the bench product (i.e. candidate molecules)and further validation, limited production and clinicaltesting

FIND To accelerate development, evaluation and appropriateuse of affordable diagnostic tools (TB diagnostics)

HHVI Reach phase II clinical trials by 2010

IAVI Eight to 12 novel vaccine candidates into clinical trials,and advance the best two or three to final-stagetesting (phase III) by 2007

IOWH • To obtain regulatory approval for Paromomycin inIndia by 2005 for visceral leishmaniasis

• Chagas disease K777

• To develop one drug or vaccine against bacterial-induced diarrhoea

• Malaria

IPM To accelerate the discovery, development andaccessibility of safe and effective microbicides

MDP To complete phase I trials of one or more microbicidecandidates by 2005 and phase III by 2008

MMV One new drug every five years, with the first one by2010

MVI To accelerate the development and accessibility of safeand effective malaria vaccines

PDVI Reach phase III efficacy studies by 2006

SAAVI To develop an affordable and effective HIV vaccine assoon as possible

TB Alliance To scale up the pipeline to deliver improvements in TBtherapy. First new drug for registration by 2010

Source: IPPPH, based on responses from organizations where received, or fromtheir websites, as of early 2004

Table 3. PD PPP portfolios

PPP Portfolio

Current

Pre-clinical Phase I Phase II Phase III

Aeras 2

DNDi*** 3

EMVI

FIND 1 1 1

HHVI 2

IAVI 2 2 1

IOWH 3 1 1

IPM

MDP 1 1

MMV 14 in discovery 4 2 2

MVI 8 6 1

PDVI

SAAVI** 6 0

TB Alliance* 10 0 1 0

TOTAL 47 16 7 8

Of which drugs 26 8 5 8

Vaccines 19 8 2 0

Sources: IPPPH, based on responses from organizations where received, or fromtheir websites, as of early 2004; and interviews.* TB Alliance anticipates a portfolio of three phase I trials and that their

current phase II trial will enter phase III before 2007. Their portfolio alsoincludes platform-related investments.

** SAAVI have none of their own products at phase I yet but collaborate on twoprojects which are at this stage.

*** DNDi have two malaria drugs in phase III partly financed by the EuropeanUnion.



9 0

A methodology for estimating financing needsA model of R&D portfolio cost for PD PPPsFive elements are necessary to build a model to esti-mate PD PPP R&D costs over a defined period:

• Understanding target output objectives (in termsof licensed new products per annum).

• Estimating attrition or failure rates for projects ateach stage of the R&D process.

• Identifying the expected cost per project at eachstage of development.

• Deducting those parts of the development processthat the PD PPP will not be funding itself, i.e. in-kind contributions from industry or other bodies.

• Specifying the resultant costs per time period of theprojects that will be under way during the periodunder consideration.1

In-kind contributions are discussed in the next sec-tion. These might comprise the possibility to obtainprojects/products that are already part of the waythrough the development process at below cost, or theundertaking of activity by a third party at less than the“full price” they would expect as a commercial sub-contractor.

A simple way of starting to understand what financ-ing might be required and the complications involvedin deriving estimates is to look at the cost of bringinga drug/vaccine through the R&D process to obtain alicence. We look at the PD PPP estimates of attritionrates, costs per project, timelines and the implied totalcost of developing a drug or vaccine. We begin by look-ing at the DiMasi et al. (2003) estimate of the costs ofdrug development, which are based on actual drugdevelopment costs for a sample of products.

The DiMasi et al. estimate of the costs of drug developmentThe DiMasi et al. (2003) estimate of US$802 million(in 2000 US dollars) for the costs of bringing a newdrug to market is much cited. Table 4 sets out thebasis upon which it is built. It comprises:

• actual mean out-of-pocket costs for phases I–III fora random sample of 68 products developed by 10major R&D–based companies (US$132.6m);

• the use of overall R&D spend data to include inpre-clinical development (e.g., discovery) costs of30% (adding US$26.0m to the cost);

• success rates for these projects, i.e., the probabilityof moving from one stage to the next (transitionalprobabilities), giving an expected cost of develop-ing a drug of US$86.6m; and

• adjusting for failures using the overall success ratefrom entry into phase I to successful New DrugApproval (NDA) of 0.215 to give total out-of-pocket costs of US$403m.

The balance of cost (US$399m) is represented by theopportunity cost of capital. This is not relevant to thePD PPPs which do not have to provide a return oncapital other than via achieving a high social benefit totheir activities.2

The table shows that 4.65 products need to enterclinical development in order to achieve one licensedproduct. The structure of this model is used to esti-mate PD PPP development costs using PD PPP-specific data on costs and attrition rates.

Estimates of attrition rates by PD PPPsWe obtained estimates of PD PPP specific attrition ratesfrom the following sources:

• MMV Business Plan 2003–07 (2003)• TB Alliance commissioned study, The economics of

TB drug development (2001)• DNDi Business Plan (2003)• an analysis of vaccine attrition rates by Struck (1998),

which looks at the probabilities of success from ananalysis of 591 vaccine candidates between 1983–94. It may, therefore, not be an accurate represen-tation of the likely success rates of current vaccinecandidates

• Boston Consulting Group (BCG study, The Econom-ics of Microbicide Development: a case for investment.

1 This can be done with various degrees of sophistication to takeaccount of the uncertainty around both success rates and costs.One approach is to use probabilistic sensitivity analysis, wherebyeach parameter is assigned a distribution, and project success/cost results associated with simultaneously selecting randomvalues from those distributions are recorded in a Monte Carlosimulation of the model. MMV used this approach in develop-ing its business plan.

2 Of course, there remains a social opportunity cost of capitalsupplied to the PD PPPs and this may be higher than thatsupplied to the pharmaceutical industry. Hard-pressed donorbudgets may have a number of alternative uses, many of whichmay yield high social returns.

9 1

We also draw on earlier work by Towse and Jamison(2003) and Towse and Mestre Ferrandiz (2003). Forcomparative purposes we also included the DiMasinumbers. The results are set out in Table 5. Some simi-larities in the numbers are apparent, but there are alsosignificant differences.

Estimates of cost per phase by PD PPPsUsing the same sources as above, except for substitut-ing the IAVI Scientific Blueprint numbers for the Struckattrition rates, we again get a significant range of costestimates for each phase of development (Table 6).

Table 4. DiMasi et al. estimates of the numbers of compounds and amount of expenditure required by phase to take onesuccessful compound to market approval

Stage Pre-clinical Phase I Phase II Phase III LAT* Total

Transitional probabilities 1.0 0.71 0.442 0.685 0.685 0.215

Number of compounds required 4.65 4.65 3.3 1.46 1.46 1

Average cost per phase per compound (in US$ millions) 26.0 15.2 23.5 86.3 5.2 156.2

Expected cost per phase (in US$ millions) 26.0 15.2 16.7 27.1 1.6 86.6

Total cost per successful compound (in US$ millions) 120.9 70.7 77.6 126.0 7.6 402.8

Percentage of total out-of-pocket R&D spend 30 18 19 31 2 100

* LAT = long-term animal testing

Table 5. Transition probabilities of success by phase

MMV TB Alliance DNDi Vaccines (Struck) DiMasi at al. BCG

Discovery— early 0.3— lead identification 0.65 0.55 0.3— lead optimization 0.55

Pre-clinical 0.55 0.1 0.63 0.56 0.5

Phase I 0.7 0.3 0.72 0.71 0.75

Phase II 0.5 0.5 0.24 0.79 0.442 0.75

Phase III 0.65 0.65 0.68 0.685 0.25

Registration/approval 0.95 0.90

NDA overall 0.0134 0.0098 0.08 0.22 0.215 0.019

NDA clinical phases only 0.2275 0.098 0.24 0.39 0.215 0.1406

Sources: MMV (2003), GATBDD (2001), DNDi (2003), Struck (1998), DiMasi et al. (2003), BCG.

Possible sources of cost differencesThere are major differences in cost in the discovery/pre-clinical and clinical phases. We do not have enoughinformation to understand possible reasons for the dif-ferences in the discovery and pre-clinical phases. How-ever, differences in cost in the clinical phases appear toreflect differences in the numbers of trials, lengths oftrials, numbers of patients per trial and cost per patientper trial.

Whilst we would expect these to vary by disease area,and to be different for vaccines as compared to phar-maceuticals, it is not clear why there is such variation.It would be beneficial to both donors and PD PPPs if



9 2

they understood the basis of the cost projections acrossdifferent PD PPPs.

Drug versus vaccines: clinical development costsOne source of difference in costs is that betweenvaccines and drugs. The major differences betweendrugs and vaccines include:

• Failure rates and attrition data. Statistical data onfailure and attrition rates are very poor for vaccines.This is largely because of the small portfolio sizesbut also reflects the belief that all the ‘easy’ vaccineshave already been developed and, therefore, futurefailure rates may not resemble those seen in the past.

• Portfolio size. Typically, a commercial operation mayscreen and conduct pre-clinical testing on up to 100new chemical entities (NCEs). Vaccines, by contrast,may be tested with only two or three variants in a‘portfolio’. Vaccine development, if unsuccessful,may be abandoned at pre-clinical stages.

• Risky science. The efficacy and toxicity are greaterunknowns in a vaccine trial than in a drug trial. Thisis another important reason why the ‘hurdle costs’of taking a vaccine into clinical testing may be muchgreater than for a drug. A candidate vaccine reliesless on transferable knowledge in previous trials.

• Trial size and cohort studies. Since the main cost ofany clinical trial is the per-subject cost, the necessityto run much larger trials for a vaccine than for adrug increases the cost significantly. Vaccine trialsrequire that healthy subjects are included in the sam-ple. Preventative trials (and trials for TB drugs forcomplex reasons) typically need much larger study

Table 6. Estimates of cost per phase by PD PPP (in US$ millions)

MMV TB Alliance DNDi IAVI DiMasi et al. BCG

Total discovery and pre-clinical 8.33 18.6 16.2 20.0 26.0 4.5

Phase I 1.58 0.6 15.2 2.0

Phase II 1.15 3.4 23.5 3.0

Phase III 9.5 22.6 30.0 86.3 46.0

Total clinical 12.23 26.6 24.2 37.0 125.0 51.0

Other 1.5 8.0 50.0 5.2 1.0

Sources: MMV (2003); GATBDD (2001); DNDi (2003); IAVI (2000); DiMasi et al. (2003); BCG

7.0

populations. Thus drug trials, such as those antici-pated by MMV, may cost around US$10 millionbecause the numbers of patients are assumed to besmall (fewer than 2,000) and the cost per patientrelatively low (below US$10,000 including the costsof analysing the trial). A large vaccine trial for a newHIV vaccine, however, could cost between US$50million and US$120 million1 and possibly more.This may include no allowance for capacity build-ing or infrastructure. From the financial resourcerequirement perspective, the size and cost of clini-cal trials is the most important difference betweenvaccine and drug development.

• Infrastructure costs. When estimating the clinicaldevelopment costs for a vaccine or NCE, it is im-portant to distinguish between the costs of conduct-ing a trial and the cost of putting the infrastructureor capacity in place to run the trial. Scientists agreethat vaccine trials require the final factory productand hence capacity building is required much ear-lier in the clinical trial phase than with drug devel-opment. This can essentially be treated as a sunkcost if the trial fails. A detailed analysis of capacity-building costs is presented in Annex 9k (J. Sadoff).

Estimates of timelinesEstimates of development time vary but not as muchas the cost and attrition rates.

1 The prime-boost NIH-led HIV/AIDS vaccine trial currentlyrunning in Thailand is expected to cost US$119 million.

9 3

Estimates of total R&D cost for a product for PD PPPsWe have combined the attrition rates in Table 5 withthe cost per project stage set out in Table 6.

In the case of IAVI we combined cost estimates takenfrom the 2000 Scientific Blueprint with the Struck(1998) vaccine attrition numbers. The results for fourPD PPPs (see Table 8) show remarkably consistentestimates of total R&D cost per product, ranging fromUS$128 million to US$192 million. However, thereis enormous variability in the balance of cost as be-tween discovery/pre-clinical and clinical developmentcosts. In addition the IAVI figures must be treated withcaution. Phase III trials are assumed to cost US$30million, which may be low. The Struck attrition rates,based on older vaccines, may also be too low. The

Table 7. Comparison of timelines

MMV TB Alliance DNDi IAVI DiMasi et al. BCG(streamlined)

Months Months Months Months Months Months

Discovery and pre-clinical 96 — 60 30 52 36

Phase I 12 19 30 12 18

Phase II 12 24 60 26 18

Phase III 24 36 36–48 34 36–48

Approval 12 6 18 12

Total clinical 60 85 60 72 90 84

Years 5.0 7.1 5 6.0 7.5 7

Total 156 — 120 102 142 126

Years 13 — 10 8.5 11.8 10.5

Sources: MMV (2003); GATBDD (2001); DNDi (2003); IAVI (2000); DiMasi et al. (2003); BCG.

Table 8. Comparing overall expected out-of-pocket costs (in US$ millions)

MMV* TB Alliance DNDi IAVI DiMasi et al. BCG

Discovery and pre-clinical 62 43 120 52 121 97

Clinical 66 128 72 118 282 803

Total 128 171 192 170 403 900

* We assume that the probability of success in discovery is equal to one. However, much higher numbers are obtained if we use probabilities found in MMV (2003) for thedifferent stages in discovery.

Sources: MMV (2003); GATBDD (2001); DNDi (2003); IAVI (2000); DiMasi et al. (2003); BCG.

BCG’s microbicides number is high – more than twicethe DiMasi et al. figure. This reflects the assumed lowsuccess rates as shown in Table 5.

Overall, we have found enormous variability in thekey estimates that would make up a portfolio analysisof a PD PPP, notably in attrition rates and cost-per-phase. Whilst these appear to net out in overall esti-mates of product development costs for four PPPs, theysuggest that great caution must be exercised in esti-mating PD PPP financial requirements.

Estimating in-kind contributionsIn-kind contributions are usually thought of as indus-try contributions, but in principle others can providefor a PD PPP to have access to goods and services at



9 4

no cost or at a price below market value (such as USAIDor the EDCTP funding clinical trials).

Kettler and White (2003), in looking at valuing in-dustry contributions, make a distinction between con-tracts (where the company is providing specifiedservices) and shared partnerships, which can be thoughtof as joint ventures that require significant, collabora-tive work on strategic direction as well as on opera-tional detail. Development/licensing agreements maybe of either kind. They give two examples: the TB Al-liance/Chiron deal on PA824 as a contract productlicensing deal whereby TB Alliance pays a licence feeand funds the pre-clinical and clinical development ofthe product1 and an MMV agreement with GSK for‘LAPDAP+Artesunate’ as a shared partnership.

For the provision of contracted services the com-pany may be: (a) fully compensated; (b) compensatedat below market prices; or (c) not compensated at all.The provision of services at below market value repre-sents an ‘in-kind’ contribution. Kettler and White notethat in-kind contributions of great potential value toPPPs include:

• participation of senior people on boards, scien-tific committees and project groups;

• involvement of senior people in project manage-ment;

• donation of products and licences;• making available compound libraries and screen-

ing facilities; and• donation and/or discounting of equipment.

Incorporating estimates of in-kind contributions intoPD PPP funding requirements is difficult. Perhaps themost important and the most difficult area is productlicensing. The announcement by IPM to in-license amicrobicide product, TMC120, from Tibotec2 illus-trates the issues well. IPM will finance clinical devel-opment and so will not save money at that point.However, it has been given a promising product thathas been through phase I trials. It would have cost

significant sums of money to have developed a prod-uct to that stage. IPM will receive royalties if Tibotecchooses to sell the product in developed country mar-kets. In shared partnerships it may be even more diffi-cult to assess the value of the contribution to the PPP.Moreover, in both licensing and shared developmentdeals the exact arrangements are usually confidential.3

In-kind contributions are extremely important, par-ticularly where there is a potential developed countrymarket or where other ‘pull’ incentives exist that willmake a pharmaceutical company willing to undertakepre-clinical and clinical research. However, they aredifficult to assess.

Estimating the financing needs of the PD PPPsWe undertook the analysis of PD PPP financing re-quirements using a number of different approaches.

Building up a ‘required’ portfolioWe set out above a methodology for developing andcosting a portfolio based on the required outputs andlikely success rates. However, only two PD PPPs havedeveloped detailed portfolio approaches – MMV andDNDi. Examples of their approaches are shown in Fig-ures 1 and 2. Given the lack of data from the other PDPPPs we did not think it appropriate to devote time tosecond-guessing these two PD PPPs as part of this ex-ercise. Nor was it possible for us, given the data andtime constraints, to develop robust estimates of theportfolio requirements of the other PD PPPs. Such anexercise would only be possible with clarification ofPD PPP objectives and an understanding of their ex-pectations on attrition rates, costs per phase and in-kind contributions.

Instead we used three more ad hoc approaches.

Estimating the funding gapTable 9 shows the PD PPP funding gap.

Using PD PPP estimates of the cumulative fundingpledges they have received and a mix of sources forcumulative resource requirements, we found for thefour PD PPPs we have been looking at plus IPM, agap of around US$2 billion over the next four years. IfIPM is not included, the gap is around US$1.2 bil-lion.

1 Chiron retains a ‘grant-back’ option to make and sell the prod-uct in richer countries, in which case it repays the TB Alliancefor the development costs.

2 Tibotec is owned by Johnson & Johnson.3 It will often make sense to both parties to keep details confi-

dential to avoid ‘spillover effects’ into other deals. For a dis-cussion of spillover effects in the context of prices, see Danzonand Towse (2003).

9 5

Figure 1. Extract from the MMV Business Plan 2003

Figure 2. Extract from the DNDi Business Plan 2003: Evolution of the portfolio 2000–201410

5

0

-5

-10

-15

2003 2006 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Num

ber o

f pro

ject

s

New projects Failed projects Registered drugs

New Projects Registered Failedprojects in portfolio drugs projects

2003 5 5 0 02004 3 7 0 -12005 3 8 1 -22006 2 7 3 -32007 2 7 3 -42008 2 8 4 -52009 2 7 5 -72010 2 8 5 -82011 2 8 6 -92012 2 8 6 -112013 2 8 7 -122014 2 8 7 -14

Table 9. PD PPP funding pledges and implied shortfall (in US$ millions)

Cumulative funding PPP estimate of cumulativepledged to 2007 required resources to 2007 Implied shortfall

IAVI 340 1,036 696IPM 94.5 775* 680TB Alliance 42 249 207DNDi 30 255 225MMV 97 152 55Total 604 2,467 1,863* Of this, BCG estimate that IPM require US$267m in early stage funding and US$508m in late-stage funding.Sources: IPPPH (based on responses from organizations where received, or from their website, as of early 2004), DNDi (2003); IAVI Scientific Blueprint (2000); BCG; MMVBusiness Plan 2003–07.

3 2

1 1 1

2 2 1

3 1 2 1 1

1 2 1

1 1 1 1 1

Portfolio Plan (as of 2003): Five Projects added every other year

Same funding pattern assumed thereafter

% cumulative probability of having drugs approved

■ 77% probability of yielding one drug by 2010■ 75% probability of a second drug by 2015

100

80

60

40

20

0

2004

2000

2000

2000

2000

2000

2000

2000

2000

2006 2008 2010 2012 2014

3–4 year time horizon

1 or more newdrugs approved




■ 3–4 year time horizon between drugs at equal outcome probabilities■ Total project costs from 2003–2007: $135 million and stabilizing



9 6

The development costs of the existing portfolioWe looked at the portfolio for the PD PPPs set out inTable 3 and used assumptions about project cost andattrition rates taken from Tables 4–8. We distinguishedbetween drugs and vaccines. For vaccines, we usedStruck attrition rates (Struck, 1998) and IAVI meancosts per phase (IAVI, 2000). For drugs, we used DNDiattrition rates and costs per phase (DNDi, 2003). Otherpossibilities can be used to calculate development costsof the existing portfolio; however, under these assump-tions, the numbers came out at US$720m for vaccinesand US$730m for drugs, making a total ofUS$1,450m. It should be borne in mind, however,that the PD PPPs are still building their portfolios.

The costs of bringing a product to licenceA third rule of thumb would be to assume that each ofthe 14 PD PPPs included in our analysis brought oneproduct to market at an average out-of-pocket cost ofUS$160m (roughly in the middle of the US$128m–192m range found in Table 8). This would involvecosts of US$2.2 billion. We should note of course thatsome PD PPPs are planning to produce variations ofexisting products (such as fixed-dose combinations)which would have much lower costs than full develop-ment of a new drug or vaccine, and all PD PPPs areseeking to obtain in-kind contributions. However, thiscalculation gives an indication of possible funding re-quirements.

The range of estimated financing needsThe range is between US$1.2 billion for four PD PPPsto US$2.2bn for 14 products, depending on the as-sumptions made, which include:

• which PD PPPs are included;• size of portfolio;• attrition rates and costs; and• any offsetting contributions in-kind.

Conclusions• If donors are to achieve new licensed drugs and

vaccines for neglected diseases, then they have todeal with the low likely success rates of individualprojects. They need to manage their risk relative tothe expected gains from successfully tackling theseglobal health problems. The best way to do this isthrough a portfolio of investments. The question is

whether the portfolio approach rests with the do-nor or with the PD PPPs. Overall we conclude thatthe PD PPPs are better placed to manage a portfo-lio of projects.

• Some PD PPPs do not have quantifiable objectives.This will make it harder for donors to assess per-formance.

• Donors should seek to align funding with objec-tives. There is no point in establishing quantifiableobjectives that are out of line with the funding re-quired to achieve them. In particular, if the portfo-lio is too small relative to the objective because of alack of funding, then there will be pressure on thePD PPP to keep even unpromising projects goingin the hope of achieving their objectives. Having aportfolio that is large enough to deal with projectfailure is crucial. Conversely there is no point inpushing PD PPPs to hold a portfolio that is largerthan justified by the scientific merit of the projectsavailable. This will simply result in larger failure rateslater in the development process.

• The PD PPP estimates of discovery and develop-ment costs and project attrition rates show majordifferences in both the discovery/pre-clinical andthe clinical phases. Whilst we would expect these tovary by disease area, and to be different for vaccinesas compared to pharmaceuticals, it is not clear whythere is such variation. There would be benefit insome shared understanding between donors and PDPPPs as to the basis of project cost projections acrossdifferent PD PPPs.

• Statistical data on failure and attrition rates are verypoor for vaccines. There is a case for work to bedone in this area to better inform both PD PPPsand donors about likely success rates for portfolioplanning and financing purposes.

• Two important areas of cost need more examina-tion – manufacturing costs and investment in clini-cal trial infrastructure. Both appear to be moreimportant issues in vaccines, because of greater com-plexity.

• There is a need for a much better understanding ofthe potential value of in-kind benefits from indus-try and others. In the case of industry this will inpart be linked to the availability of other ‘push’ and‘pull’ incentives which should provide the commer-cial incentive to encourage companies to provide

9 7

more in-kind benefits when they partner with PDPPPs.

• There appears to be a large gap between the fund-ing available to PD PPPs and the finances they arelikely to need to get products to market. Donorsand PD PPPs need to improve their understandingof the likely size of the gap and how it might befilled.

ReferencesBoston Consulting Group. The Economics of Micro-

bicide Development: a case for investment.Danzon P, and Towse A, (2003). Differential Pricing

for Pharmaceuticals: Reconciling Access, R&D andPatents. Journal of Health Care Financing and Eco-nomics Volume 3, Issue 3:183–205

DiMasi, JA, Hansen, RW, Grabowski, HG, (2003)Theprice of innovation: new estimates of drug develop-ment costs. Journal of Health Economics 22: 151–185.

DNDi Business Plan (2003).The Global Alliance for TB Drug Development (2001).

The economics of TB drug development. The Glo-bal Alliance for TB Drug Development.

Henderson R, and Cockburn IM, (1996). Scale, Scopeand Spillovers: The Determinants of Research Pro-ductivity in Drug Discovery. RAND Journal of Eco-nomics 27 1:32–59.

IAVI Scientific BluePrint (2000). Accelerating GlobalEfforts in AIDS Vaccine Development.

Kettler, H, and White, K, (2003). Valuing industry con-tributions to public-private partnerships for health.Draft Report for IPPPH Advisory Board. Institutefor Global Health.

Kettler H, and Towse A, (2002). Public Private Part-nerships for Research and Development: Medicinesand Vaccines for Diseases of Poverty. Office ofHealth Economics.

Medicines for Malaria Venture (2003). Business Plan2003–2007. Medicines for Malaria Venture.

Struck M, (1998). Vaccine;14:1998: 1301–1302.Towse A, and Jamison,D, (2003). The Economics of

Pharmaceutical R&D for Key LDC diseases. Work-ing Paper for the World Bank Technical Consulta-tive Group on Health and Pharmaceuticals.

Towse, A, and Mestre Ferrandiz J, (2003). WorkingPaper on NCE costs. The Office of Health Eco-nomics,.

Widdus, R. et al., (2001) “Towards better defining‘public-private partnerships’ for health”, draft, Ini-tiative on Public-Private Partnership for Health,Geneva.


ANNEX 9B

The emerging landscape of public-private partnershipsfor product development1

Alison Sander (Consultant, USA) and Roy Widdus (IPPPH, Switzerland)

• What defining characteristics do the 17 PD PPPsshare?

• How do these entities differ from one another andwhat accounts for the variation in how each PD PPPis addressing its mission?

• Are there any early observations about which of thesevariations matter in terms of helping a PD PPP toreach its stated goals?

This is an opportune time to ask these questions. De-veloping a new drug or vaccine is a challenging andexpensive process that can take 8–15 years and requireshundreds of million dollars for a single product. Al-though many of the PD PPPs considered here are lessthan three years old and have just embarked on thelong, complex research and development process, oth-ers, such as the International AIDS Vaccine Initiative(IAVI), have been working to develop an HIV/AIDSvaccine since 1996. Comparing practices and ap-proaches across the 17 PD PPPs can help us see wherepractices converge, understand the areas where enti-ties are pursing different strategies, and discoverwhether there are any initial hypotheses on practicesthat are likely to increase the success of these venturesboth individually and collectively.

It is also an important time to look at the emerging‘field’ of PD PPPs. Although to date donors have com-mitted an impressive sum (at least US$1.2 billion) andthere are many signs of progress, substantial additionalresources will be required if this field is going to leadto the development of multiple products. The PD PPPfield itself may need to move from a series of individualdonors backing individual projects to more of a port-folio approach in which donors collectively look at thesums that will be required for success, at the areas wherenew donors or expertise will be required, and at the

Executive summary

Over the past decade more than 25 public-privatepartnerships have been created to develop prod-

ucts for some of the most urgent public health priori-ties.2 These are not-for-profit ventures formed todevelop products to combat diseases that predomi-nantly affect populations in low- and middle-incomecountries.3 This field has now attracted more thanUS$1.2 billion and a cadre of top management talentto support a series of targeted efforts to developspecific products for specific diseases.

This paper examines the practices of 17 of theseproduct development public-private partnerships (PDPPPs) to understand what these ventures have in com-mon and to look at the variations in how each PD PPPis approaching its particular mission. Specifically, thispaper addresses three key questions:

1 We would like to express our appreciation for the research con-tributions provided by Sandra Botta and Katie Storey and forthe assistance provided by each of the 17 PD PPPs covered inthis paper. The article is the sole responsibility of the authors.Any comments are welcome to [email protected] [email protected]

2 These 25 are listed within the 100 or so PPPs on developingcountry health problems identified by the Initiative on Public-Private Partnerships for Health (IPPPH). See the Partnershipsdatabase at www.ippph.org.

3 For convenience, these ventures are termed product develop-ment public-private partnerships (PD PPPs) and their targetsare referred to as ‘neglected diseases’. It is worth noting thatwhile very few individuals favour the term ‘public-private part-nership’ because it is so general, no better alternative has beenfound. In this paper the term ‘public’ includes the govern-ment, multilateral institutions and public academic institutions.The term ‘private’ includes for-profit businesses (including butnot limited to pharmaceutical and biotech companies), privatefor-profit laboratories and the not-for-profit foundations es-tablished by the major pharmaceutical companies. A separatecategory is used for donors, foundations and not-for-profitentities.


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areas where it may make sense to share platforms orexpertise across initiatives.

This paper is intended as a first attempt to establishsome shared frameworks and terminology in this im-portant field. Product development has been describedas both an art and a science. It is as important to un-derstand at an early phase not only what is known inproduct development for neglected diseases but alsoto ask what is not known. The authors hope that asthe field evolves, future versions of this paper can cap-ture the progress and obstacles in individual PD PPPapproaches as well as at the collective level.

Defining characteristics of PD PPPsAt their core, the 17 PD PPPs covered in this papershare five defining characteristics:

• They use some private sector approaches to attackresearch and development challenges.

• They target one or more ‘neglected diseases’.• They use or intend to use variants of the portfolio

management approach.• Their primary objective is public health rather than

a commercial goal.• They are focused on developing products specifi-

cally suited for use in developing countries.

Variation among PD PPPsBeyond these characteristics, substantial variation ex-ists among the PD PPPs. This variation is examined infour broad areas: strategic variation; financial variation;variation in contributions and roles of the public andprivate sectors; and operational variation. Some of thisvariation follows from the mission that each PD PPPhas taken on. PD PPPs make initial core choices ofwhich disease to tackle and which product to develop.Once these choices have been made, each PD PPP findsitself in a specific landscape where the private sector isor isn’t present, where there is or is not a downstreamdistribution system, where there are or are not late stagecompounds to test and so on. So, for example, thechallenges facing ventures such as Areas, which is try-ing to develop a TB vaccine, are likely to be differentfrom those facing DNDi, which is working on findinga drug for Chagas disease.

Some of the variation comes from strategic choicesmade about how to partner, with whom to partner,

how much to outsource, how much to build in down-stream considerations and the like. These strategic andoperational choices include the scope of activities topursue, the approach to partnering, the mix of exper-tise sought, the way the portfolio is created and man-aged, and the role of external oversight bodies inmonitoring the process. For example, the breadth andscope of activity undertaken along the research-devel-opment-access continuum is a key strategic choice.Specifically, advocacy and education are considered coreactivities for many of the PD PPPs but not all. All PDPPPs undertake communications advocacy to mobi-lize resources for their own programme of work, but afew PD PPPs have undertaken a more extensive advo-cacy agenda devoting significant resources and dedi-cated staff of up to ten employees to these activities.Some PD PPPs see access and distribution as a down-stream issue to be explored once a product is devel-oped, while other PD PPPs believe this is a critical areafor focus from the beginning.

Most PD PPPs are set up as virtual R&D enterprisesand hence make extensive use of contracting, whichbrings its own challenges.1 For each type of variationconsidered, the goal is to identify the common prac-tice or norm (if one has been established) and to showthe range of difference around the norm. There is notyet an established methodology for describing the pa-rameters on which PD PPPs can be compared, but thispaper examines the following areas of variation.

Strategic variations• Product/disease target focus.• Scope of activity along the research-development-

access continuum.• Independent versus ‘hosted’ legal status.

1 A risk with a virtual R&D/contract model is that contractorsmay not have an incentive to spot early problems in their re-search. Also, there may not be anyone asking the integratingquestions across the various steps. Coordinating whether theproduct could be manufactured at a reasonable price, whetherthe regulators would approve such a product, whether and howthe financing will be available to procure such a product allrequire advanced coordination and project management skillsof a very complex process that may be happening at differenttimes for different candidates.

A N N E X 9 B . T H E E M E R G I N G L A N D S C A P E O F P U B L I C - P R I V A T E P A R T N E R S H I P S F O R P R O D U C T D E V E L O P M E N T

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Financial variations• Degree to which functions are done in-house or

contracted out.• Size of committed funding.• Donor base, breadth and duration.

Sector roles and contributions• Engagement and partnering with business sector,

particularly pharmaceutical firms and/or biotech-nology companies.

• Engagement with full range of public sector col-laborators.

• Mix of expertise.• Value of in-kind contributions and nature of contri-

butions.

Operational variations• Portfolio development and management approach.• Degree of adoption of business-like practices as

measured by published materials.• Governance and accountability mechanisms.

Early hypothesis on variations that matterStrategic and operational choices can influence boththe cost to achieve a mission and the likelihood of suc-cess. It is too early to judge what paths will work best,but it is not too early to share a sense of some of thebest practices that have emerged. The individuals in-terviewed for this paper include representatives fromeach PD PPP and from three of the largest donors fund-ing the field. Donors are quick to state that there is nosingle formula for success. Individual missions requireunique combinations and approaches to pull togetherthe expertise and resources, and to craft the strategyrequired to develop a product. There are a number ofconditions, however, that those donors interviewedpoint to as important to increase the chance of suc-cess. They are:

• A clearly defined mission with a well articulated goal(e.g., new malaria drug by 2010).

• Adequate financing for the initial phases of missionand projection of total financing required to meetthe end goal.

• A top management team with access to the best sci-ence and a track record in product development.

• A plan that clearly identifies the steps to be taken,by whom and when.

• Active and independent oversight from an experi-enced board.

• A partnering strategy that includes real collabora-tion from partners who have the expertise required.

• A robust portfolio with rigorous portfolio manage-ment processes.

Donors who were interviewed for this paper affirm thatthe indicators they look to in measuring the progressfor a PD PPP are: a top management team; an activeindependent board; an active partnering strategy withstrong partners; and a robust portfolio.

A partnering strategy requires obtaining access tothe expertise required to move through the long andexpensive product development process and to developa product that will work in the setting for which it isintended. Today, much of the upstream and develop-ment expertise lies in the private sector where largepharmaceutical companies and some biotech compa-nies have track records of navigating the process fromlead candidates, through clinical trials to product reg-istration.1 Much of the downstream expertise residesin clinicians and national health authorities, who un-derstand the circumstances in which individuals withtarget diseases present themselves and the settings inwhich prevention, diagnosis or treatment need to oc-cur. Ultimately, to develop products that work in thesesettings (e.g., for upstream solutions that will work onthe downstream end) will require partnering with arange of different types of participants.

Portfolio management is critical because productdevelopment is such a risky and lengthy process. First,a diversified portfolio increases the chance of successby reducing the reliance on a small number of candi-dates with similar characteristics. Second, robust port-folio-management processes are required to ensure thatcandidates that do not meet the desired specificationsor clinical trial hurdles are actively weeded out, allow-ing money to be invested in other candidates and dif-ferent approaches. Evidence of active pruning is oneof the signs that gives donors a sense of confidencethat portfolio management techniques are being used.

The paper also discusses three tensions that will bedifferent in each PD PPP but that are important to

1 Beyond the simple question of with whom to partner is theharder question of how to involve partners. Should partnersbe given IP rights, paid for their services or asked for broadversus targeted support?

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manage. First, each PD PPP needs to find the rightbalance between a focus on upstream science and down-stream access issues. A second area that is challengingin any virtual R&D process, particularly if there areseparate contracts with different organizations, is man-aging the multiple interface points. These include placeswhere hand-offs are expected or where different con-tractors are involved. At a high level, the interface pointsinclude the clinical trial sites, the research labs, the pro-curement and distribution ends, manufacturing andregulatory approval. A third tension to manage is tohave the long-term agreements that are needed forintellectual property (IP) issues and for regulatory ap-proval but that ensure adequate flexibility with con-tractors during the development phase.1 Some of theolder PD PPPs, which have entered into collaborationswith larger pharmaceutical companies, now have broadagreements rather than project-specific terms to cre-ate flexible terms of collaboration rather than ones tiedto a specific compound.

ConclusionAlthough PD PPPs have not produced any new licensedproduct yet, there are many early positive signs. Theseinclude both direct and indirect measures, such as:

• Direct fund raising success.• Early pipeline successes.• New attention to some neglected diseases by some

major pharmaceutical companies and selected bio-technology firms.

• Early advocacy and education successes.• Development of some infrastructure including clini-

cal trial networks.• New collaborations between the North and South

and some emphasis on capacity building.• Development of a cadre of management talent, able

and willing to apply private sector models to publicsector neglected-disease challenges.

It is clear from the levels of public and private funding,the number of products being tested, the trials beingconducted and other indicators that much progress hasbeen made. Yet, there are signs that more support is

needed if the field is going to bear fruit. As the PDPPP field moves from an initial start-up period intooperations, both PD PPPs and donors may want tothink about the following four issues:

• How should the PD PPP field be defined – how dowe build a shared definition about what we are track-ing?

• What resources are required to support and sustainthe field and how can the donor pool be expanded?

• What expertise is required from key sectors, andshould specific sectors be targeted for increased par-ticipation?

• Are there places where greater coordination couldimprove the chances of success?

In addition there are several factors that are not atpresent calculated by PD PPPs in a consistent form,but that could be helpful in attracting new donors tothe field and in evaluating the potential for success ifthey were tracked or reported on a consistent basis.These include:

• Potential public health impact if the product is de-veloped.

• Maturity of the science and degree of scientific chal-lenge.

• Existence of demand for a product from cliniciansand national health officials.

• Existence (or lack) of efficient downstream coun-try-level distribution systems to ensure access toanticipated products.

• Level and value of specific in-kind contributionsfrom business/pharmaceutical companies and thepublic sector.

The conference at Wellcome Trust is an important steptowards addressing these questions. Although this pa-per is ambitious in scope, the authors hope it will offera framework to orient newcomers to the field and toraise some useful questions for long-time supporters.

…

The PD PPP fieldProduct development public-private partnerships (PDPPPs) appeared in the 1990s. They arose in responseto a clear challenge. Most of the extant expertise indrug, vaccine and diagnostic development was in thefor-profit private sector, but because there was no fi-

1 This tension can be handled by good IP and legal advisers. Forexample, it is important to write into any contract agreementthat if a candidate does not work or if the PD PPP decides todrop it for portfolio reasons, the research costs can stop.



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nancial incentive to develop productsfor diseases afflicting primarily thosein low-income countries, no newdrugs or vaccines for some of hu-manity’s greatest scourges had beendeveloped.1

Public-private partnerships (PPPs)arose out of a desire to create inno-vative and effective approaches tosome of the leading global diseasechallenges by harnessing the exper-tise and knowledge of both the pri-vate and the public sectors. In the lastten years, almost 100 PPPs involv-ing the health sector have beenformed to address various aspects ofneglected diseases.2 Of these, lessthan 25 have directly taken on theresearch and development challengeand focused on product develop-ment.3 This paper looks at the cur-rent state of a selection of these PDPPP efforts. We start with what PDPPPs have in common, then explorethe many variants that have emergedand finally examine what can be con-cluded at this point in a longer-term experiment.

An innovative modelPD PPPs offer a model to address the need for new orimproved products to combat diseases of the poor forwhich prevention or treatment is lacking or inadequate

1 Tuberculosis, for example, which kills more than 1 millionpeople a year, was still treated with drugs developed more than25 years ago that require six months and four drugs in combi-nation to work, and it is still being diagnosed using a technol-ogy developed in the 1800s.

2 Neglected diseases are defined as diseases that predominantlyaffect the populations of low- and middle-income countries.There are approaches that are not covered in this paper to treat-ing these diseases, such as insecticides for malaria or condomsto prevent transmission of HIV/AIDS. It is also important torecognize that product development is not an end in itself butis a critical step in the process by which scientific knowledgefrom basic research is eventually applied to benefit health,through the distribution and ultimate use of products by tar-geted populations.

3 The rest of the PPPs in the health field address a range ofrelated issues including advocacy, downstream access challenges,education and distribution of existing products.

or that have become resistant to current treatments.These neglected diseases include HIV/AIDS, tuber-culosis, malaria and other tropical and poverty-relateddiseases. The 17 PD PPPs covered in this paper collec-tively represent more than US$1.2 billion in commit-ted funding, cover more than half of the top ten globalneglected diseases, and are attempting to produce afull array of tools from prevention (vaccines andmicrobicides), to diagnostics, to treatment (drugs).

PD PPPs emerged to fill gaps which other organi-zations could not or would not meet. Their activitiesnest within a complex web of funders, local publichealth clinics, national regulatory bodies, internationalpublic health standard-setting bodies, advocacy groupsand researchers. Each PD PPP must work with myriadother upstream and downstream actors to tackle a givenchallenge.

The success of a PD PPP will depend on its scope,the maturity of science, the ability to secure fundingfor its mission and the ability to work with other play-ers in a way that ensures that the right product is de-

Table 1. PD PPP endeavour addresses some of the top global killers

No. of people Number Committedkilled annually new cases dollars raised

Disease by disease annually PDPPP Focus to date

HIV/AIDS 2.8 million 5.5 million IAVI Vaccines $350 million

SAAVI Vaccines $45 million

IPM Microbicides $95 million

MDP Microbicides $27 million

GMP MIcrobicides $64 million

TB 1.6 million 8.0 million TB Alliance Drugs $42 million

Aeras Vaccines $108 million

Find Diagnostics $30 million

Malaria 1.2 million 300–500 million MVI Vaccines $150 million

EMVI Vaccines $18 million

MMV Drugs $107 million

Dengue fever 19 000 20 million PDVI Vaccines $56 million

Hookworm 3 000 N/A HHVI Vaccines $20 million

Leishmaniasis 51 000 1–1.5 million DNDi/IOWH Drugs $11 million (IOWH)

Chagas 14 000 16–18 million DNDi/IOWH Drugs $30 million (DNDi)

Other RotaADIP/ Vaccines $60 millionPneumoADIP

Total 5.7 million 351–553 million $1.2 billion

Source: Health data: WHO 2002; economic data: survey of PD PPPs for this paper, as of early 2003.

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veloped and that it gets to those who need it most.The variables that many funders look at are the scopeof activities undertaken, the potential for impact, thestate of the science, and the likelihood of success.

PD PPPs are described as a hybrid model becausethey must tap product development expertise of theprivate sector to achieve a social goal. These are oftenambitious undertakings in the sense that, althoughmany private sector companies are working on this area,no one has yet developed, for example, an AIDs vac-cine. The mission includes upstream challenges in termsof the basic science, funding testing and modifying alead candidate. If successful on the upstream side, thereare then downstream challenges of registering the prod-uct, manufacturing it at a cost-effective price and find-ing a way to get it to people who may live in remoterural areas with little infrastructure.

When undertaken in the private sector, this processfrom basic science to distribution can cost more thanUS$600 million and take at least 8–12 years for a newdrug. The expectation is that the process would bepossible at lower cost and take less time for a neglecteddisease but we lack good data on this.

Since part of the PD PPP model is an attempt torecreate the advantages of the private sector’s success-ful research model – both the scale advantages of bigpharma and the agility advantages of biotech – it isworth elucidating what those sources of advantages are.Both large pharmaceutical companies with extensiveR&D track records and smaller biotech companies havedeveloped three areas of advantage: 1) employees withtrack records and well-honed capabilities; 2) infrastruc-ture incorporating the latest technologies; and 3) proc-esses designed to keep all parts focused on efficiency,profitable product creation and rapid weeding out ofnon-performing products. Although large pharmaceu-tical firms are increasingly beginning to contract outservices, most still have integrated value chains for prod-uct development that ensure that products being de-veloped run the full gauntlet of checks and tests.

A shared portfolio approach to the R&D challengeThe 17 PD PPPs discussed in this paper share five de-fining characteristics:

• They use some private sector approaches to attackresearch and development challenges.

• They target one or more ‘neglected diseases’.

• They use or intend to use variants of the portfoliomanagement approach.

• Their primary objective is public health, rather thana commercial, goal.

• They are focused on developing products specifi-cally suited for use in developing countries.

Wide variation on other dimensionsAlthough all these organizations have a fundamentallysimilar goal – ensuring development of successful


Table 2. PD PPPs described in terms of four key areasof variation

STRATEGIC MODELFOCUS TARGET DISEASE SCOPE AFFILIATIONS

Drugs Multiple Basic research HostedDiagnostics Hookworm Development Independent

Other products Dengue AccessVaccines Malaria Advocacy

TBHIV/AIDS

Other

FINANCIAL MODELAPPROACH SIZE DONOR BASE COMMITMENTS

Subcontract-all $10m Sole-sourced One-timeVirtual R&D $50m Multiple Single-year

Sub-contract $100m Broad-based Multi-yearpieces $150m

Fully-integrated $200m$300m

SECTOR ROLES/CONTRIBUTIONTYPE MIX

CONTRIBUTORS CONTRIBUTION EXPERTISE VALUE IN-KIND

NGOs Expertise 100% public $0Government Board Largely public $10m

Biotech participation 50-50 mix $15mPharmaceutical In-kind Largely private $25m

Products 100% private $50mDollars

OPERATIONS MODELPORTFOLIO EXTERNAL

BUSINESS PORTFOLIO DEVELOPMENT ACCOUNTABILITY/ MODEL CONTRIBUTION DECISION BODY GOVERNANCE

Business plans Arms length Teams Independent BoardScientific- Licensed Portfolio of Directorsblueprint in-house committee Independent

Pharmaco- Largely Scientific stakeholdereconomic report in-house advisory association

Advocacy All developed committee Independentroadmap in-house All clinical

Access plan trials oversight

Source: Author interviews with individual PD PPPs.


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diagnostics (FIND), while three others (IPM, MDP,GMP) are focused on developing microbicide prod-ucts to prevent transmission primarily of HIV/AIDS.

The challenge undertaken in terms of disease andproducts affects how many potential partners there are.For HIV/AIDS, because of the prevalence of the dis-ease in many wealthy countries, there are a number ofprivate sector companies competing to develop anAIDS vaccine. For diseases that afflict only people inthe poorest countries, it may be very difficult to findany private sector company in the developed worldinterested in partnering. For diseases such as TB, whichhave been on the public health radar screen for years,there are extensive compliance regimes and distribu-tion systems in many developing countries, so it maybe easier to distribute any drugs developed.1 For prod-ucts like microbicides, which are novel and do notmatch traditional approaches, there may be no exist-ing distribution system on which to ‘piggyback’.

Table 3. Timeline for development of PD PPPs

Source: PD PPP interviews and summary sheets in Appendix.

1996 1997 1998 1999 2000 2001 2002 2003IAVITDR/

Precursorto FIND

Sequella/Aeras

EMVI MMVMVI

SAAVI

TB AllianceHHVIIOWHGMP

MDP IPMPDVI

DNDiFIND

Rota-ADIPPneumo-

ADIP

product(s) – they differ on a number of pa-rameters. Some variations follow from the corechoices in disease and product. Other varia-tions, such the breadth of activities, use of otherparties, and degree of independence or affilia-tion, follow from the strategic approacheschosen.

Differences in approachThe next section discusses implications of vari-ation for the extent of financing required andfor the likelihood of success. This section fo-cuses on four categories of variation: strategicvariation, financial variation, sector-role varia-tion, and operating-role variation.

Some of this variation follows from designchoices, some from the timing, mission, andstate of play in each PD PPP. The earlier PDPPPs have had more time to develop their port-folio management techniques, to develop abroader donor base, and to develop a full setof partners. More than half of the 17 PD PPPshave been in existence for less than four years,and so are just beginning to develop a range of prod-ucts. They have not yet had a chance to move intodownstream activities or to build a robust portfolio.

Each PD PPP has chosen to address one or moredisease(s) and one or more type of product(s) (drug,vaccine, diagnostic or other). This choice affects thecomplexity of its mission in terms of the maturity ofthe science required, the presence or absence of col-laborators, the infrastructure available to help with dis-tribution, the cost to achieve the goal and the ultimatesize of the benefit if the goal is achieved. Table 4 be-low shows that many of the PD PPPs have chosen tofocus on the top three killers among neglected dis-eases: HIV/AIDS, TB, and malaria. Although drugsand vaccines are the most common products beingworked on, one PD PPP is focused on developing TB

Table 4. Seventeen PD PPPs cover a broad range of diseases and foci

Other

Chagas

Leishmaniasis1

Hookworm

Dengue fever

Malaria

TB

HIV/AIDS

DNDiIOWH

(Latin America)

PneumoADIPRota ADIP

IOWH(Diarrheal)

DNDi

IOWH(India)DNDi

HHVI

PDVI

Aeras FIND TB Alliance

MMVEMVIMVI

IAVISAAVI

IPMMDPGMP

Sleepingsickness

Vaccines Products/microbicides

Diagnostics Drugs

Prevention Treatment

T A

R G

E T

F O C U S

1 Cutaneous and visceralSource: PD PPP interviews and summary sheets in Appendix.

1 WHO has a DOTS (directly observed therapy, short-course)surveillance programme for distributing TB drugs and moni-toring compliance in more than 180 countries.

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Strategic variationsDisease target and product focusDeciding which disease to target and what typeof product to develop is the starting point forany PD PPP. The rationale for the selection var-ies from tackling the disease with the greatestmortality and hence the potential for the great-est impact, to tackling the disease and productwhere the science is most advanced, boostingthe probability of success. Some of the diseaseschosen, such as HIV/AIDS, are the focus ofmany organizations; others, such as Chagas dis-ease and leishmaniasis, have received very littleattention and may be considered as the mostneglected. There are also a few PD PPPs whose mis-sion is to target several diseases (e.g., DNDi seekingdrugs for malaria, leishmaniasis and Chagas disease).In the case of IOWH, their aim is to develop vaccinesor drugs for multiple diseases (Chagas disease, leish-maniasis, malaria and diarrhoeal diseases).

Independent versus hostedIn many cases, the next decision the founders of a PDPPP make is whether to operate independently (whichis the case for eight of the 17 PD PPPs consideredhere) or whether to be hosted in an organization. Somedonors have strong views about whether independentor hosted initiatives are more likely to succeed (see Table11 on selected donor views), whereas others see thedecision purely on a case-by-case basis, favouring

affiliation where there is existing infrastructure and sci-ence and favouring independence where there is a needto work with many separate research entities. If theinitiative is going to be hosted, key decisions need tobe made about where the PPP will be housed and whatthe terms of the hosting arrangement will be.

Breadth and scope of activity along the research-development-access continuumThis dimension captures information about which ac-tivities in the continuum from basic research to down-stream distribution PD PPPs are now doing and whichactivities they plan to do in the future. Table 6 showsscope of activity planned for sample PD PPPs in termsof their current and future focus on activities from ba-sic research, discovery, development, and access. Im-portant choices need to be made in terms of approachto a given activity and the emphasis placed upon it.For example, PD PPPs vary in their methods of pursu-ing strategies on access and advocacy and even what isunderstood, or meant by each term differs across enti-ties.

In general most of the PD PPPs focus on early-stagediscovery and candidate development. About half cur-rently concentrate on downstream access issues and theother half see this as one of their future priorities. Noneof the PD PPPs have yet reached the point where full-scale manufacturing is part of their current focus. Re-search, discovery and development are the upstreamand mid-stream parts of the process. Approaches varymore widely in the downstream activities of manufac-turing a licensed candidate and distributing it.


Table 5. PD PPPs: independent or hosted entities

Independent Hosted (Host)

IAVI SAAVI (MRC-RSA)FIND TBDI (WHO/TDR)Aeras EMVI (Centre for International Health,MMV Bergen University, Norway)IOWH MVI (PATH)

TB Alliance HHVI (Sabin Vaccine Insitute)IPM PDVI (International Vaccine Institute)

DNDi MDP (Imperial College ScienceTechnology & Medicine)

GMP (CONRAD)Rota–ADIP (PATH)

Pneumo–ADIP (Johns Hopkins BloombergSchool of Public Health)

Source: IPPPH Partnership Database – www.ippph.org.

Source: Author interviews with PD PPPs and summary sheets in Appendix.

Table 6. PD PPPs: variation by activity focus for sample approaches

Basicresearch

Discovery/Design

Preclinicalanimalmodels

Regulatoryapproval

Manu-facturing Procurement Logistics/

Distribution

Development Production AccessClinical

P1 P2 P3

Currently do Intend to do by 2007

Comprehensive approach, e.g., IAVI

Targeted approach, e.g., Pnemo-ADIP, PDVI

Start-up approach, e.g., FIND


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Basic researchBasic research is not a priority activity for most PDPPPs. Most basic research takes place in academic orresearch institutions and the PD PPPs that do engagein it do so through collaboration with these partners.Most PD PPPs engage at the level of discovery and theearly stages of translation between basic and applied re-search. For drug development, this is the stage wherebiological targets, as well as molecules (‘candidates’)which are able to act on these targets, are identified.

Discovery/designDiscovery/design is where most of the PD PPPs be-gin the process, reviewing what is known in terms ofthe basic science and the need, and beginning to iden-tify lead candidates that have promising characteris-tics.1 For each PD PPP, discovery/design is a coreactivity although there are choices (described in thenext section) in terms of how much of this activity isdone in-house versus how much is contracted out.

Development and clinical trialsDevelopment typically involves conducting large-scaleclinical trials in several parts of the world to test theefficacy of different candidates.2 This is a step that most,but not all, PD PPPs see as part of their core mandate.

Regulatory approvalAlthough regulatory approval is already a core activityfor most PD PPPs, many see it as a core focus for thefuture. Any candidate product proven safe and effec-

tive in clinical trials needs regulatory approval in eachof the countries in which it will be marketed or used.The development process for new pharmaceuticals isgeared to generating convincing evidence of productsafety and efficacy in the target populations, to stand-ards that will satisfy national regulatory agencies. Thesemay include the United States’ FDA or the EuropeanMedicines Evaluation Agency, which coordinates ap-plications in the EU, as well as those of disease-en-demic countries (DECs). This means trials must bedesigned meticulously and conducted to Good Clini-cal Practice (GCP) standards. Meeting these stringentstandards has to be built into all the product develop-ment activities supported by any PD PPP and means itmust have access to specialist expertise in regulatoryaffairs. They can obtain this expertise by hiring suchstaff (as has IPM), by contracting for it (as does MMVfor some of its projects), or by leaving it to the com-mercial collaborators to provide (as does MMV forother projects).

ProductionLarge-scale manufacturing (for amounts beyond thoseneeded for clinical trials) is planned for the future by anumber of the PD PPPs. Few if any PD PPPs currentlyhave the facilities to manufacture a licensed compoundthemselves, but several plan to form licensing agree-ments with existing manufacturers in developing coun-tries to ensure low-cost versions of the product.

Distribution and accessDistribution and access are also activities where PDPPPs have chosen very different approaches. Some PDPPPs see access as a downstream issue to be dealt withafter a product is developed, while others think it isimportant from early stages. For some PD PPPs, cre-ating a distribution plan is central to their mission whileothers believe they can hand off their product to anexisting distribution system. Access in this sense cov-ers planning for those downstream activities that willinfluence or facilitate intended beneficiary populationsgetting the anticipated product, including its afforda-bility. Access issues thus include:

• Assessing, identifying and supporting planning fordistribution.

• Developing a product with performance character-istics that are suitable for those environments (pack-

1 In drug discovery lead compounds are ‘optimized’, meaningthat the compound is manipulated to improve its biological ortherapeutic properties. Then compounds are transformed intoformulations that can be produced as the dosage forms for usein pre-clinical studies.

2 Preclinical studies are used to confirm the candidates’ biologi-cal safety, activity and toxicology profile. If a candidate passesthe pre-clinical step then the PD PPP applies to governmentregulatory authorities for permission for human clinical test-ing. The clinical trial process is divided into different phases.Using the example from drug development, initial human tests,called Phase I studies, usually involve a small number (20–80)of healthy volunteers and are conducted primarily to assess thesafety and tolerability at various dose levels. Phase II studiesinvolve administering the drug to a larger number (50–500)of patients who are diagnosed with the disease being studiedto obtain preliminary information on clinical efficacy and de-termine the optimum dose. Phase III studies are much largerin scale (often several hundred to many thousands of patients)to confirm the safety and effectiveness in the intended patientpopulation.

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aging, temperature stability, minimal infrastructurerequirements, etc.).

• Anticipating, and in some cases arranging for,financing needed for product procurement.

• Ensuring that there are no unanticipated regulatoryhurdles.

• Ensuring access to product manufacturing capacityat a reasonable cost.

• Ensuring adequate health services infrastructure,usually the responsibility of governments.

Addressing access issues creates the need to work withpotential collaborators different from those encoun-tered in product development. These may includemanufacturers, international institutions such as theWorld Bank, bilateral aid agencies, developing coun-try disease control programmes, local clinicians whounderstand the needs and infrastructure available onthe ground, local health officials who influence utili-zation, as well as a host of others.1 The nature of ac-tivities to ensure target population access may differwith product type and the existence and proficiency of‘downstream’ actors. For example:

• Children’s vaccines enter a reasonably well estab-lished distribution system.

• Vaccines for adults or adolescents, or microbicidespresently have few downstream actors in place for a‘hand-off ’.

• Some products enter reasonably proficient utiliza-tion systems (e.g. TB control programmes) whereasin other cases there is little access infrastructure inplace (e.g. malaria).

While donors have different perspectives on the righttiming and focus that access issues should have in thelife of a PD PPP, most agree that PD PPPs need tohave examined the relevant access questions and to haveidentified what actions will be required to ensure an-ticipated products are put into use without delay. Thescientific hurdles in developing a product are half ofthe battle. Figuring out how these new tools can bedeployed in countries facing extreme financial and in-frastructure challenges is the other.

Advocacy and educationAdvocacy and education activities take place through-out the process rather than at one point in the devel-opment cycle. They are considered core activities for

many of the PD PPPs, but what activities a PD PPPengages in, how big a staff is dedicated to the task,who they partner with and what they desire to com-municate all vary across PD PPPs. All PD PPPs under-take communications advocacy to mobilize resourcesfor their own programme of work.2 But a number ofPD PPPs have undertaken a more extensive advocacyagenda, devoting significant resources and up to tenemployees to these activities.

Advocacy and communication activities may beroughly classified as mission related, disease related, oreducational communications. Mission-related advocacyincludes efforts to promote action by others that willassist the organization to accomplish its mission.3 Dis-ease related advocacy includes efforts to raise aware-ness of the need for more attention to a disease/product, not for a specific PD PPP. Examples includethe efforts of the TB Alliance, IAVI and DNDi in theirrespective fields. Educational communications broadlysupply information on recent developments to non-specialized audiences. Each of these advocacy effortscan help to move awareness of a whole field forward.PD PPPs vary in the extent to which they take on ad-vocacy and communications activities beyond those fortheir own resource mobilization (and hence survival);this variation represents true choices on how to allocateresources and on the role that a PD PPP should play.

Implications of strategic choicesProbably the most important decision a PD PPP makesis what mission to take on. The disease and productfocus determine the degree of challenge and the ulti-mate impact if the initiative is successful. The missionaffects whether there are other players present withwhom to partner, the willingness of donors to fundthe enterprise, the basic pattern of epidemiology and


1 Recent debates in malaria treatment (including LapDap(chlorproguanil/dapsone) and artemisinin-based combinationtherapies (ACTs)) highlight the need for ensuring such con-versations take place early rather than late in the process. SeeAttaran A et al. ‘WHO, The Global Fund, and Medical Mal-practice in Malaria Treatment’ The Lancet; 363:237–40. 2004.This article was followed by the WHO Response to Accusa-tions of Medical Malpractice by RBM/WHO, and the GlobalFund to Fight AIDS, TB and Malaria. (See WHO website:www.who.int)

2 Usually this is limited to potential funders, but in the case ofsome it includes the general public (e.g. MSF-DNDi).

3 This category includes the advocacy for international regula-tory harmonization and clarification by IAVI, IPM and FIND.


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whether there are scientific precedents that need to beimproved upon or whether this is an entirely novelenterprise.

For example, PD PPPs committed to work in thefield of tuberculosis find a large need, science that hasnot been improved over many decades, and an exten-sive implementation and distribution system for TBdrugs through the WHO DOTS programme, as wellas a system for procuring affordable new drugs throughthe Global Drug Facility.

PD PPPs focusing on HIV/AIDS work with veryactive and successful advocacy and education groupsand have a number of leading private sector compa-nies working in the same area (since HIV/AIDS isperceived to present an important market opportunity).They therefore have a large number of basic research-ers working on both vaccines and drugs. However, inpoorer countries no real distribution systems currentlyexist for public health products like vaccines that aretargeted to reach adults and adolescents.

Microbicides represent a completely new class ofpharmaceutical products. There is no regulatory prec-edent for a topical vaginal cream to prevent the spreadof sexually transmitted infections. The microbicide-focused PD PPPs (for example, IPM, GMP, and MDP)need to think through new research and regulatorychallenges and how the product would be distributed,among other novel first-order questions.

There is a key distinction in terms of degree of sci-entific challenge and level of novelty each PD PPP haschosen to undertake. Some PD PPPs mainly seek toreplace products for which there are many precedents.PD PPPs in this category, such as MMV or the TBAlliance, can build on known pathways and processesto achieve their goal. Other PD PPPs are trying toestablish the first effective vaccine or drug for a diseasefor which there is no precedent (e.g., MVI, IAVI,HHVI). And microbicides can be argued to be tryingto establish a new class of health products for whichonly distantly related analogous products exist.

A second key implication from the core choices isthe potential for public health impact. Diseases targetedby PD PPPs differ considerably in the size of thepopulations affected, in terms of age (children versusadults), geographic distribution, health impairment(death, disability, acute, chronic) and socio-economicstatus of populations affected. While some of theseelements include highly subjective value decisions, thePD PPP field might benefit from some thinking aroundthe public health potential from a given mission.1 Al-though some donors prefer to work on problems thathave the greatest likelihood of success, others preferthe challenges with the greatest potential for impact,even if they are more difficult and riskier. There are no‘right’ or ‘wrong’ areas in the neglected-disease land-scape, but it is important to understand the terrain onehas chosen and to adapt a strategy to that choice.2

Different neglected disease challenges lead to dif-

1 In-house versus contracted, use of partners, hosted versus independent.2 Portfolio development and management, governance model.Source: A. Sander

Managementteam and skills

Cost to fund anddonor base

Strategicapproach1

Operationsmodel2

Potentialpartners &

collaborations

Potentialfor improvement

Productfocus

Breadthand scope

Corefocus

Diseasefocus

Late stageproductsavailable

Extent ofpublic health

need

Currentproductsavailable

Maturingof

science

Degree of challenge Potential impact

Strategicchoices

Context

Table 7. Core choices affect context, degree of challengeand potential impact

1 Some PD PPPs have utilized disease burden or potential pub-lic health impact estimates in building a case for their exist-ence and support. However, these efforts have not beensystematic or easy to compare. Some methods do exist, albeitnot universally accepted, to compare the relative health bur-dens of disparate diseases. These include the calculation of dis-ability adjusted life years (DALYs) and other measures(QUALYs or quality- adjusted life years, etc.). More difficultis the development of estimates of potential public health im-pact of envisaged products. This would entail predicting vari-ous inputs, e.g. population likely to be reached, usage rates,effectiveness, etc., as well as other variables.

2 Most funders are willing to embark on a more expensive andmore complex task if the payoff is a vaccine that could preventseveral million deaths a year. It is beyond the scope of thispaper to look at comparisons of impact and risk, but each do-nor is presumably forming its own portfolio of riskier PD PPPswith higher potential impact and PD PPPs with smaller poten-tial impact but more certainty of success. Different donors mayalso have different risk profiles and objectives for whether theywant to be on a high feasibility versus high impact but riskierendeavour.

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ferent strategic choices. What all PD PPPs have in com-mon is the need for strategies that are clearly articu-lated and that take into account a number of factors.Specifically the strategy for PD PPPs should include:

• A mission for a product with active demand fromDECs.

• A mission where the science is sufficiently matureand capable of success if sufficient resources areraised.

• A clearly articulated goal and time frame.• A scope that leverages rather than duplicates activi-

ties already being done by others.

Financial model variationApproachIn principle, most of the PD PPPs are set up as virtualresearch and development operations. For most, thegoal is to be able to have a lean staff, not to own a lotof infrastructure and to be able to contract or workwith the best service providers for each stage of thedevelopment process. In reality, however, each steprequires a separate decision: will it be done in house,outside but under the careful supervision of in-housestaff, or outside and at arm’s length? The sum of thesedecisions influences the amount of financing a PD PPPrequires and its balance between control and agility.1

Some PD PPPs have chosen to invest in developingtheir own network of clinical trial sites (e.g., IPM).Others have chosen to work with groups that are de-veloping clinical trial sites, to ‘piggyback’ on clinicaltrial sites already developed by their partners (e.g.,MMV to a certain extent), or to have an in-house clinicaltrials expert supervise a series of contracted trial sites.

Although few of the PD PPPs have yet reached themanufacturing stage, this will be another point wheresimilar choices will need to be made. PD PPPs are notlikely to own their own manufacturing facilities but

will probably contract to a capable manufacturer in thedeveloping world. Advocacy and education are a lower-cost activity and one that many PD PPPs have optedto do in-house although usually in coordination withother outside groups. Almost all the PD PPPs have anadvocacy/education director and some have built awhole department around this capacity.

In some cases the approach will be dictated bywhether potential partners or contractors are available.In the case of microbicides or of IAVI, which hopes todeliver AIDS vaccines to adults, there may not be anexisting delivery structure and greater involvement bythe PPP in building a solution may be required. In allcases, decisions on approach, on what needs to be donein-house or outside and whether the work should beclosely controlled or fully outsourced need to be madeat each point in the value chain on the basis of somecombination of cost, criticality, capabilities, flexibility,scale, and availability.

If PD PPPs opt to contract many elements to createa virtual R&D approach, it will be essential to managethe interface points (e.g., the linkages across functionsand activities). The risk with many separate contractsis that no one asks the integrating questions. An in-house team will have to work closely with the contrac-tor team to anticipate relevant activity in future stages,build in agility and the ability to update and/or prunethe portfolio, and to ensure that there are enough peo-ple with incentives to ask challenging questions. With-out this active oversight, the risk is that contractors,who may have an incentive to see a stream of workinvolved in a project continue, may not ask the type oftough or integrative questions that they would ask ifthe process were in-house.

Size of the entityThere are a number of ways to measure size. One canuse committed funds (but this tends to favour the PDPPPs that have been around longer), annual budget,number of professional employees or another indica-tor. As of early 2004 the 17 PD PPPs included in thisstudy have committed funds ranging from US$10 mil-lion to US$350 million. The key factor is not size it-self but whether the funds raised are enough to meetthe mission selected. Larger or better-funded PD PPPscan support a bigger portfolio, have more in-houseexpertise, and afford to take on more steps. Those that

1 Owning the infrastructure or having the expertise in-househas advantages in terms of control but can be quite expensiveand may not make sense if the expertise exists in many placesalready. Contracting can give a PD PPP flexibility in terms ofchoice of partner and can be a way to lower infrastructure costs,but can leave the PD PPP with less control, depending onhow the agreement is written. There can also be risks in con-tracting that make it harder for a PD PPP to change courselater on. Where activities are left (without written agreement)to unpaid collaborators, for example in the plan to ‘hand-off ’downstream activities to other organizations, the PD PPP canbe at risk if these players do not perform adequately.


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Table 8. PD PPP funding sources

PD PPPsDISEASE/PRODUCT HIV/AIDS HIV/AIDS Malaria Malaria TB TB TB/Other

Vaccines Microbicides Drugs Vaccines Drugs Vaccines Diagnostics Other “Neglected Diseases”

GMP/ TB Rota PneumoFUNDERS IAVI SAAVI IPM CONRAD MDP MMV MVI EMVI Alliance AERAS FIND DNDi IOWH PDVI HHVI ADIP ADIP

FOUNDATIONS

Bill & Melinda Gates Foundation + + + + + + + + + + + + +

Ellison Medical Foundation +

Rockefeller Foundation + + + + + +

The Wellcome Trust +

Other foundations + + + + +

GOVERNMENT BILATERAL AID AGENCIES

Canadian Government (CIDA) +

Government of Denmark (DANIDA) + + +

Government of the Netherlands + + + + +

Government of Norway + +

Development Cooperation Ireland + + +

Swiss Government (DEZA/SDC) +

Swedish Government (SIDA) + +

U.K. Government (DFID) + + + +

USAID + + + + +

OTHER GOVERNMENT FUNDING

Government of South Africa +

National Institute of Health (NIH), USA + + +

Centers for Disease Control (CDC) +

MULTILATERAL AGENCIES

European Union + + +

UNDP

UNAIDS +

UNFPA + +

WHO + + +

The World Bank + + +

NGO

Médecins Sans Frontières (MSF) +

BUSINESS

Pharma + + +

Others + + + +

OTHERS

+ + +

Source: Responses from PD PPPs to IPPPH survey, where received; in other cases organizations’ websites.

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are less well funded focus on filling a specific targetedgap and generally try to reduce the need for in-houseexpertise.

The donor base and duration of commitmentPD PPPs have attracted different donor bases. Half ofthe PD PPPs exist on funding from a single donor,while the other 50% have three or more donors. Ingeneral, having a broad base of funders is thought toincrease stability, although a very fragmented donorbase, which expects different goals, can present its ownchallenges. Together, the 17 PD PPPs have attractedfunding from more than 60 donors based in more than15 countries.

Funders for the PD PPPs range from private foun-dations to governments to NGOs. The type of donormay have an influence on the strategy and approach ofthe PD PPP. For example, EMVI, the European ma-laria vaccine initiative funded by EU member statesand the European Commission, takes a different ap-proach to that of MVI, which is funded by the Bill &Melinda Gates Foundation. The commitments maycome in single-year tranches or be for several years.Multi-year commitments are greatly preferred by PDPPPs because they make planning easier.

Implication of financial choicesInitially, donors were willing to be sole funders for aPD PPP, but increasingly PD PPPs are looking forbroad bases of support and for a financial base thatmatches the ambition of the mission. As the numberof PD PPPs grows and as some PD PPPs begin to en-ter more expensive phases involving clinical trials, theissue of ensuring financial sustainability for individualPD PPPs and for the field as a whole looms larger.Although the universe of donors has grown, that ofPD PPPs has grown faster. Initial estimates suggest thatsubstantial amounts will be required over the comingyears in order to get over the hurdles required to de-velop products. Increasingly, donors will look to PDPPPs to see if they have a reasonable financial plan andif they have a clear grasp of the total funding requiredto meet their life-cycle goal, not just the funds requiredto get to the next milestone.

There are not necessary right or wrong answers interms of size and funds required. Different neglected-disease challenges require different financial resources.


What PD PPPs have in common is the need for finan-cial models that take into account the following:

• Financing sufficient to meet initial phases of themission.

• Financial projections of total life cycle requirementto meet end goal.

• Strong financing base with broad set of funders.• Funding based on multi-year commitments.

Sector roles and contributionsAnother area donors are scrutinizing more closely thanin the past is the role that partners, and particularlypartners from the private sector, play in a PD PPP andthe amount and type of contribution they are plan-ning for the future. The definition of public-privatepartnership is quite loose and hence includes signifi-cant variation. The 17 PD PPPs were asked to ratefour items in terms of per cent participation comingfrom the different sectors: the management team; theboard; committed capital; and influences on their re-search model.

Table 9 shows the range of variation, from PD PPPswith almost no private sector background in their man-

Table 9. Sector participation and contributions

Source: Author interviews of PD PPPs and summary sheets in Appendix.

Public sector Private sector Donor/foundation Not ratio

* Does not include in-kind contributions

Aeras

DNDi

EMVI

FIND

GMP

HHVI

IAVI

IOWH

IPM

MDP

MMV

MVI

PDVI

Rota-ADIP

Pneumo-ADIP

SAAVI

TB Alliance

Background ofmanagement

team

Backgroundof

Board

Amount ofcapital

contributed*

Perceptions ofinfluence inR&D model


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agement teams and boards to PD PPPs that come pre-dominantly from the private sector.

Nature of contributors‘Contributors’ refers to:

• Organizations that provide the capital for PD PPPs.• Companies and organizations that supply expertise

and other in-kind resources.• NGOs and local community organizations that pro-

vide access to local knowledge about how to make aproduct useful and get it successfully distributed.

On-the-ground expertise in DECs is also beginningto be tracked (e.g., the TB Alliance, DNDi, IAVI andothers). Some PD PPPs (e.g., IAVI and the TB Alli-ance) have stakeholder associations to link to leadingglobal NGOs and to multinational and local organiza-tions in DECs. These groups link to the organizationsthat have power in the disease control community fortheir respective product/disease. In some PD PPPs thestakeholder association has a voice in some of the deci-sions but in others it is only an advisory group.

Type of contributionThere are a number of ways partners and donors cancontribute to a PD PPP, and the best-run PD PPPsseem able to increase and expand these relations, ob-taining network and positioning advice from theirdonors, scientific advice from top experts, access toleading infrastructure from their partners, and criticalin-country expertise from local health and NGO part-ners. The types of contribution can be grouped in termsof expertise and talent (which can be in the form of aseconded employee or access to top experts), candi-date products (lead compounds, licensing rights forpart or all of the world), infrastructure (lab equipment,clinical trial access, manufacturing access, etc.) or on-the-ground access and expertise.

The total financial support for the 17 PD PPPs ismore than US$1.2 billion. In-kind support comes froma broader range of collaborators, including pharma-ceutical companies, smaller biotech firms, research labo-ratories and developed and developing countrygovernments and ministries of health. The value of thein-kind contributions is hard to calculate and not yetstandardized in spite of several valiant efforts.1 Lessthan half of the PD PPPs had an estimate for the value

of any in-kind support. The lack of a consistent meth-odology makes it hard to draw conclusions but thenumbers cited for in-kind contributions ranged fromless than US$500,000 in two cases to over US$20million for IAVI and MMV. In MMV’s case, reportedin-kind contributions were equal to almost 25% of thetotal capital committed.

Some PD PPPs have much greater private sectorparticipation and in-kind contributions. However, suchcontributions are easier to obtain when the venturetargets a disease area or product that the private sectorcares about but is not actively competing in. The PDPPPs that have expanded downstream (e.g., IAVI) havemuch greater NGO and stakeholder participation. Tounderstand the value of the collaboration it is neces-sary to distinguish between partnerships where thereis only a loose agreement to collaborate (possibly onlyfor a single project) and integral partnerships with manypoints of collaboration and exchange. An example ofan integral partnership would be MMV’s agreementwith GlaxoSmithKline, which covers multiple researchprojects and includes collaboration of personnel, can-didates and infrastructure over a number of years.

Mix of expertiseThe far right column of Table 9 above registers thesubjective perception of the mix of influences on a PDPPP’s R&D approach. This perception often corre-lates with the mix of expertise hired. At one extreme,PD PPPs that view themselves as largely copying pri-vate sector models may be more likely to push for thegreatest rigour (‘up-or-out mentality’) in managingtheir portfolios and tend to have a laser focus on theR&D part of the challenge. At the other end, PD PPPsthat view themselves as largely public interest (e.g.DNDi) are likely to assign a high priority to buildingcapacity in developing countries and to involve diversedeveloping country stakeholders. These latter PD PPPshave taken a particularly keen interest in questions ofadvocacy and access. And PD PPPs that view them-selves as part of the hybrid model may see themselvesas combining the rigours of private sector portfoliomanagement with access, advocacy, capacity building

1 Kettler H and White K, May 2003, Valuing Industry In-KindContributions to Public Private Product Development Partner-ships. Initiative on Public-Private Partnerships for Health,Geneva.

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and focus on the non-profit world. The PD PPPs thathave emerged offer a range of models, which offerdifferent approaches to resolving any public-privatetensions.

Implications of sector choices and contributionsIncreasingly donors recognize that success in productdevelopment depends in part on getting the necessaryexpertise. This can come from hiring individuals andorganizations with track records in product develop-ment. It can also be obtained by partnering with anorganization with the expertise, infrastructure andprocesses, or it can be bought (by licensing a later-stage candidate or contract manufacturing).

Each PD PPP has its own challenge and its own mixof organizations that may be interested in collaborat-ing or willing to collaborate, but each needs to be surethat its partnering strategy is maximizing access to thetypes of expertise required. Similarly, on the down-stream side, for PD PPPs with a focus on getting prod-ucts into the hands of individuals, it is important tofocus on getting collaboration from key NGOs, publichealth officials and local health authorities in the rel-evant geographical areas. The type of partners requireddepends on whether the bigger challenge is upstream,midstream, downstream or all of these.

While much of the optimal partnering strategy de-pends on the challenge selected, there are a few com-mon guidelines:

• Leverage, don’t duplicate, existing platforms andknowledge.

• Obtain private sector contributions that reflect realinvolvement at multiple levels – in management,governance and in-kind contributions.

• Identify a network of scientists and organizationsattacking similar problems, position the PD PPPwithin such a network and learn from similar en-deavours.

• Involve stakeholders and individuals in developingcountries early rather than late in the process. Thisis important for all PD PPPs and particularly essen-tial for those with downstream focus.

Operations modelElements of the business model1

Since many PD PPPs use private sector business prac-tices and portfolio management to develop products

for neglected diseases, it is useful to look at some sam-ple practices and techniques. Several of the PD PPPshave adopted processes and published materials alongthe lines of those used by the private sector to planlonger-term strategy. These include developing a busi-ness plan, creating a scientific blueprint, doing pharmaco-economics studies, developing an advocacy road map,and in some cases developing an access plan. In reality,all of these are needed as they reflect different parts ofthe environment a PD PPP must assess and navigate.

Although some PD PPPs, such as IAVI, have draftedeach of these documents and made them available ontheir web sites, that practice is not universal. More than65% of the 17 PPPs have a comprehensive businessplan that describes the strategy and organization struc-ture to meet their mission, spells out the financialrequirements for the next five years, and begins to ad-dress basic questions about the resources that will berequired. Some 41% have developed a pharmaco-economic report, a publication that looks at the mar-ket-demand side for a given tool, examines the epide-miology and where the geographic need exists, andincludes economic forecasting about the size of thispotential market if a product were available.

Of the 17 PD PPPs, 64% have a scientific blueprint.This document examines the state of the science todayand develops a plan, often a portfolio plan, for whereand how to invest to get to an end product. It usuallyincludes what is and is not yet known in the basic sci-ence and a list of those involved in research and devel-opment. The PD PPPs that have not published ascientific road map have probably thought about theseissues but either have not published a formal plan orhave a plan that is for internal use only. Only 29% havean access plan and 18% an advocacy road map.

Although published materials are not the only signof what business practices are used, they are a goodproxy for what issues have been thought through andwhether there is a plan that has been jointly agreed to.Gaps in a comprehensive assessment in terms of whatis needed to develop and put a product into use maymean the PD PPP is in danger of missing importantactivities that it or others must do for ultimate success.


1 As measured by published available materials that address keyelements of a PD PPP’s strategy – such as a business plan, ascientific blueprint, a pharmaco-economics assessment of themarket size, an advocacy road map, and an access plan.


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Most of the PD PPPs have established clear milestonesand metrics to measure progress toward a long-termgoal, but only a few have taken the added step of pub-lishing and sharing these in a way that allows inter-ested parties beyond the board to see the progress.

Portfolio state of developmentBeyond the differences in philosophy, business prac-tices and published strategies, there are important dif-ferences in whether the PD PPP plans to develop itsown portfolio and how robust or diversified the port-folio is intended to be. The PD PPP distinction wasoriginally intended for PPPs that had committed toand embarked on plans to develop a new product us-ing advanced portfolio management techniques of di-versification, pruning and risk balancing.

That strict definition is challenging, because someof the PD PPPs intending to develop portfolios haveonly recently started up and are licensing their firstcandidates. Others do not plan to form their ownrobust portfolio of candidates because they are aug-menting the efforts of a private sector company thatalready has a product but has not adapted it to devel-oping world needs. In that case it may not make sensefor a PD PPP to develop its own portfolio. The bestexamples in this category of augmenting private sectorefforts are GAVI’s two ADIPs (Accelerated Develop-ment and Introduction Plans). GAVI has put togethera large portfolio of vaccines that have been or could bedeveloped and has chosen to spend US$60 million tosee whether the existing pneumococcus vaccine soldby Wyeth and the two vaccines for rotavirus that areclose to being marketed could be adapted for the de-veloping world.

Clearly it takes fewer resources and staff to augmentor adapt an existing private sector product than to cre-ate a whole portfolio of candidates that need to betested and taken through the full development cycleof clinical trials.

Portfolio characteristicsA number of characteristics indicate how robust a port-folio is. At the highest level, these relate to the size,diversity and quality of the candidates in the portfolio.A portfolio that includes candidates at different stagesof development (for example, pre-clinical or phase I,II or III testing) may be considered the most diversi-

fied, but creating this advanced state may take consid-erable time when there are no existing late-stage prod-ucts. At the next level, the quality of the portfolio is afunction of the questions that have or have not beenanticipated. Are the potential candidates licensed forthe rights and time frame required? Are they easy tomanufacture? Are they likely to function in tropical andpoorer parts of the world?

A third layer of questions relate to active portfoliomanagement. Does the portfolio have a balance of riskyproducts with greater potential and safer bets withlower potential? Has the portfolio been pruned? Is itmeeting its milestones and has it been adjusted for theresults from clinical trials? A large portfolio thatincludes candidates that are not viewed as likely tosucceed can waste significant resources and serve as adistraction.

Portfolio managementThe majority of PD PPPs operate as virtual R&D man-agers but they still face a number of choices about port-folio management. These include whether to developthe candidates in-house or to license candidates thatothers have developed. There are also choices relatedto the approach: whether to act as a virtual R&Ddepartment or to adopt the more robust type of port-folio management exemplified by IAVI, whose 80employees include experts on each stage of the researchproblem, including manufacturing experts.

This type of integrated and expensive approachclearly is not appropriate for all of the PD PPPs. Forexample, PDVI, which is looking for a process to cre-ate a pediatric dengue vaccine, faces a different chal-lenge requiring a very different approach to portfoliomanagement. At least one company (Aventis Pasteur)is actively developing a dengue vaccine for adults whichis in late-stage clinical trials. PDVI has been charged,not with creating its own products, but rather focus-ing on whether the existing candidates can be adaptedfor children.

Depending on the original mission and the level ofprivate sector involvement, projects for the portfoliocan be developed in-house, licensed in-house or de-veloped by others at arm’s length. The tasks involvedin managing the portfolio depend on the scale of thechallenge. Only a small staff may be needed, or the PDPPP may require in-house experts who can actively

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coordinate and work with others involved at each levelof the product development challenge.

Portfolio development approachAlmost all the PD PPPs with active portfolios gothrough a similar process. There are calls for propos-als, evaluations of those proposals, teams to identifythe best approaches, and people skilled in licensing tobring in-house the best leads not being developed else-where. What differs by PD PPP, depending on the stageof development and the challenge, is the level of focuson portfolio management and the use of external over-sight to ensure that the process is carried out efficientlyand aggressively. All the PD PPPs with active portfo-lios have a chief scientific officer whose job requiresknowing the science and the best candidates and whois responsible for developing a plan to create and main-tain the most robust portfolio and for testing and dem-onstrating the efficacy of the best lead candidates. Thedistinctions are found in how this process works in eachPD PPP, and how much oversight is provided and bywhich groups. Many PD PPPs have a portfolio com-mittee, and most of those with active portfolio man-agement have an independent scientific advisorycommittee (SAC).

The oversight of the process and external revieware very important. It is not easy to drop a candidatethat has been widely touted and actively supported foryears, but this is a critical part of making the portfolioprocess work efficiently. As one head of a PD PPP ex-plained: “You have not really learned about portfoliomanagement until you have had to drop a favouredcandidate from your list.” An important check on theportfolio development process is to look at which can-didates have been dropped and when, and whetheroversight is effective. Portfolio management is not onlyabout creating and collecting the portfolio, it requiresactive screening and making tough decisions to ensurethere is a portfolio of real candidates with potential forsuccess.

Governance/accountability of the ventureHow the portfolio is managed is a subset of a set ofissues about external oversight for the PD PPP as awhole. Legally independent PD PPPs have boards ofdirectors, although this is more complex for the PDPPPs that are hosted. What differs is who is on the

board, how active the board is, how often it meets(ranging from one to five times a year) and whether itserves as a ‘rubber stamp’ board or asks challengingquestions. In some cases donors sit on the board (for-mally or ex-officio) but in many cases they do not. It isworth asking a series of questions about how effectivethe board oversight is, including:

• How extensively are board members involved?• How well do they understand the challenges of port-

folio management?• What type of expertise do they bring to the process?

The board of legally independent PD PPPs must alsoassume a number of responsibilities; key among themare providing overall risk management, ensuring fiscalaccountability and guiding the recruitment of a topmanagement team.1

In addition to a board of directors and a scientificadvisory committee, some PD PPPs have other over-sight committees, such as clinical trials or policy advi-sory committees. Again, the effectiveness of thesegroups depends on the expertise of their members, thequality of their contribution and their own sense ofaccountability. A few PD PPPs have stakeholder asso-ciations. In some cases this is just a list of organiza-tions that are working on parallel activities, but in otherPD PPPs this is a way to ensure that the populationthat is ultimately meant to benefit (patients in low-income countries) has a say in the process.

Implications of operating model choicesEach PD PPP has essentially chosen its own operatingmodel within whatever constraints are imposed by theavailability of suitable collaborators. While this guidecan suggest some important questions to ask and dis-tinctions to make, the validity and likelihood of a givenset of operating model choices depends on the mis-sion and end goal of the PD PPP and the amount offinancial resources and partners available to meet thatgoal. Those PD PPPs that are focused on upstreamactivities and on creating a full portfolio will requirean operating model that allows for robust and rigor-ous processes for selecting and licensing candidates andfor taking them through clinical trials and acting quickly


1 See IPPPH (2004), Liability and Other Legal Issues for Or-ganizations Engaged in Product Development Through Public-Private Collaboration, March, Geneva.


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on the results. PD PPPs that intend to work with theprivate sector on an existing private sector formula-tion may not need to build their own portfolio andmay be able to use a leaner team to work on focusedclinical trials and downstream issues to be sure that anexisting or late-stage product can be adapted for theneeds of developing countries. Different neglected-disease challenges require different customized ap-proaches. What all PD PPPs have in common is theneed for operating models that take into account thefollowing:

• A top management team with full capabilities re-quired to meet the goal.

• An active and independent board of directors (oroversight committee, if hosted), which representsall key sectors and which demands accountability.

• An active and independent SAC, which representsall key technologies and required expertise.

• Published materials with clear milestones and metrics.• Robust and rigorous processes for pruning projects

and overseeing portfolio development in the largerPD PPPs.

Implications of variationsIt is early in the life cycle of PD PPPs to draw anydefinitive conclusions about which design choices aremore likely to lead to the development and use of ef-fective products. However, what can be seen clearlynow is that different choices have very strong implica-tions for funding requirements and it is possible tosuggest some early hypotheses about which variationsmay be likely to correlate with success.

Some of the implications of the choices shown aboveare listed in Table 10.

Source: Author interviews with PD PPPs.

FINANCIAL MODELAPPROACH SIZE DONOR BASE COMMITMENTS

Subcontract all $10m Sole-sourced One-timeVirtual R&D $50m Multiple Single-year

Sub-contract $100m Broad-based Multi-yearpieces $150m

Fully-integrated $200m$250m$300m

IMPLICATIONS

Cost to fund, expertise available, chance for sustainability,adequacy of funding for the task

OPERATIONS MODELPORTFOLIO EXTERNAL

BUSINESS PORTFOLIO DEVELOPMENT ACCOUNTABILITY/ MODEL CONTRIBUTION DECISION BODY GOVERNANCE

Business plans Arms length Teams Independent BoardScientific- Licensed Portfolio of Directorsblueprint in-house committee Independent

Pharmaco- Largely Scientific stakeholdereconomic report in-house advisory association

Advocacy All developed committee Independentroadmap in-house All clinical

Access plan trials oversight

IMPLICATIONS

Cost to fund, likelihood of developing successful portfolio adequacyof oversight, use of private sector models

STRATEGIC MODELFOCUS TARGET DISEASE SCOPE AFFILIATIONS

Drugs Multiple Basic research HostedDiagnostics Hookworm Development Independent

Other products Dengue AccessVaccines Malaria Advocacy

TBHIV/AIDS

Other

IMPLICATIONS

Cost to fund, degree of scientific challenge, potential public healthimpact, likelihood of success

SECTOR ROLES/CONTRIBUTIONTYPE MIX

CONTRIBUTORS CONTRIBUTION EXPERTISE VALUE IN-KIND

NGOs Expertise 100% public $0Government Board Largely public $10m

Biotech participation 50-50 mix $15mPharmaceutical In-kind Largely private $25m

Products 100% private $50mDollars

IMPLICATIONS

Expertise and depth of resources available, ratio ofpublic to private sector input

Table 10. Choices and variations have implications for cost to fund and likelihood of success

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Implications for funding requiredOne of the most expensive parts of the product devel-opment process is the clinical trials carried out in phaseI, II and III testing. These are expensive because ofrecruitment costs, the labour and time involved, safetyrequirements and often the multiplicity of test sites. Ina number of cases a candidate, which has been testedat phase II level, requires modification and retesting.Therefore, if a candidate exists that has already passedearly testing (i.e., a candidate in phase III or later), itcan be licensed or modified for use in developing coun-tries, and the funding requirements for the PD PPPwill therefore be lower.

If a PD PPP has to build its own infrastructure (labo-ratory sites, clinical trial sites, or even potentially manu-facturing sites) the cost will be much higher than if itcan leverage existing facilities. Building facilities ratherthan contracting for them with others makes sense onlywhere existing facilities are not available or there is aneed for greater control.

Some potential implications for the success and sustainabilityof the ventureIt is too early to judge what paths will work best, butsome potential pitfalls can already be identified. Table11 also suggests that donors have their own views,which in many cases pull in different directions, aboutwhat choices are important and likely to correlate withsuccess.

All individuals interviewed for this paper agreed thatthere is no single formula for success and that productdevelopment is a complex process even for organiza-tions with billions of dollars and large staffs. That be-ing said, there are several conditions frequently citedas important elements to maximize the chance of suc-cess. They are:

• A clearly defined mission with a well articulated goal.• Adequate financing for the initial phases of mission

and projection of total financing required to meetthe end goal.


Table 11. Critical success factors mentioned by PD PPPs and selected donorsMENTIONED BY PPPS MENTIONED BY DONORS*

Donor A Donor B Donor C

Strategic ‘PD-PPP should have wherewithal “We look for places where You need to be “Look for a venture thatto do everything directly or science is mature and social independent in this is unique and takes aindirectly with a partner.” demand is robust.” game to take on the real stand.”“For us being independent was “We are willing to take risks challenges.”important…we need to be very but also look for low-hangingnimble and flexible to do the job.” fruit where we can have strong

impact.”

Financial “We need long-term commitments “We are willing to take risks “I look for that real sense “More funders is importantbut many donors are set up with commensurate with the of trust and rapport and serves as a kind ofannual planning cycles.” opportunity.” where they tell me their risk spreading.”

“Size and momentum in deepest concerns.”terms of a broad base offunders is important.”

Sector roles “Tremendous strength and “We like a mix of US and “It is all about people not “Need to expand gover-flexibility from ability to be placed European donors.” structure… Hire people nance to include the voicebetween private and public sector.” “We look for good leadership and find partners that of the poor.”“Nothing succeeds like success… with enough understanding have a track record.” “I feel strongly therenow business wants to be in on of the space that it doesn’t should be private sectordeals with us because their matter which sector they participation.”competitors are.” come from.”

Operating “Need management structure that “Portfolio and an economic “No one is successful to “Important to do capacityenables cold-hearted look at mindset are key.” date…these are all building in developingportfolio choices.” experiments in process.” countries.”

* At least 2–3 interviews per donor.Source: Author interviews with PD PPPs and funders.


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• A top management team with access to the best sci-ence and a track record in product development.1

• A plan that identifies the steps to be taken, by whomand when, in order to achieve the mission.

• Real collaboration from partners with the expertiserequired.

• Active and independent oversight from an experi-enced board.

• A robust portfolio with rigorous portfolio manage-ment processes.

In addition to these early hypotheses on questions thatare worth asking, there are three tensions, which willbe different in each PD PPP but which are importantto manage. First, each PD PPP needs to find the rightbalance between a concern on upstream science andon downstream access issues. Even if there is a vaccineor a new drug therapy, it is important to rememberthat a lot of other elements will be critical to ensure

that they are taken up early and widely. That beingsaid, a new PD PPP can get stretched very quickly if ittakes on extensive activities at both ends of the valuechain; focus is important.

A second area that is challenging in any virtual R&Dprocess, particularly if there are separate contracts withdifferent organizations, is managing the multiple in-terface points. These include places where ‘hand-offs’are expected or where different contractors are in-volved. At a high level, the interface points include:clinical trial sites; research labs; procurement and dis-tribution ends; manufacturing; and regulatory approval.

A third tension to manage is to have the long-termagreements for intellectual property and for regulatoryapproval, but to ensure adequate flexibility with con-tractors during the development phase. This tensioncan be handled by good IP and legal advisers but it isimportant to write into any contract agreement that ifa candidate does not work or if the PD PPP decides todrop it for portfolio reasons, the research costs canstop. Some of the larger PD PPPs, which have formedagreements with larger pharmaceutical companies, now

1 Bringing in individuals at the management team or board levelwith a product development track record can help reduce thelearning curve.

Table 12. Early hypotheses on selected critical success factors

Strategic • Clear mission for product with active demand from disease-endemic countries• Mission where science is sufficiently mature that success is possible with adequate resources• Clearly articulated goal and time-frame (e.g., new malaria drug by 2010)• Scope which is leverage activities already being done by others and which anticipates downstream access and other

important questions

Financial • Financing sufficient to meet initial phases of mission• Financial projection of total life cycle requirements to meet end goal• Strong financing base with broad set of funders• Funding based on multi-year commitments

Sector roles • Leverage and link to existing platforms and knowledge• Contributions that reflect real involvement from private sector at multiple levels in management, governance, in-kind

contributions• Identification of and positioning within network of scientists and organizations attracting similar or adjacent problems• Involvement of leading stakeholders and clnicians in developing countries early rather than late in process

Operating • Exceptional management team with full capabilities required to meet goal, that works well together, and that can adapt overlife of project

• Active board of directors which is independent and demands accountability• Active SAC which represents all key technologies and required expertise• Published material for transparency (e.g., business plan, scientific blueprint, access and advocacy plan if appropriate) with

clear milestones and metrics• Robust and rigorous processes for pruning and overseeing portfolio develpment

Source: Author interviews with PD PPPs, funders and industry.

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have blanket collaboration terms rather than project-specific terms.

ConclusionThe PD PPP field began as a collection of individualapproaches to see whether pharmaceutical industrialknowledge and tools for product development couldbe applied to neglected diseases. Although there is nonew product yet, there are many early signs of success.These include both direct and indirect measures suchas:

• Direct fund raising success.• Early pipeline successes.• Stimulation and support of a network of players.• Early advocacy and education successes, which have

helped to support new pricing and drug fundingmechanisms such as the Global Drug Facility forTB drugs.

• Development of some infrastructure including de-velopment of clinical trial networks.

• New collaborations between the North and Southand some emphasis on capacity building.

• New attention to some neglected diseases by somemajor pharmaceutical companies and selected bio-technology firms.

• Development of a cadre of management talent ableand committed to applying private sector models topublic sector neglected disease challenges.

It is clear from the levels of public and private funding,the number of products being tested, the trials beingconducted and other indicators that much progress hasbeen made. Yet, there are signs that more support isneeded if the field is going to bear fruit. Ironically, theinitial success of the model has led to a proliferation ofPPPs for health and PD PPPs. Although this can beread as an initial endorsement, the present set of fundersis unlikely to be able to support all of the initiativesbeing pursued by the current PD PPPs. This suggestsa need for financial planning by both PD PPPs anddonors to clarify the extent of the likely gap. New andadditional funding can be attracted, but that may re-quire a new level of communication and outreach.

It is an important time to look at the ‘field’ of PDPPPs that is beginning to emerge. The PD PPP fielditself may need to move from a series of individualdonors backing individual projects to more of a port-

folio approach in which donors collectively look at thesums that will be required for success and at the areaswhere new donors or expertise will be required andwhere it may make sense to share platforms or exper-tise across initiatives. As the PD PPP field moves froman initial startup period into operations, both PD PPPsand donors may want to think about some of the fol-lowing issues.

First, the need to define the PD PPP field. Is it use-ful to think of vaccine, drug, diagnostic and other prod-uct development PPPs together at the same time? Is ituseful to group organizations that are augmenting pri-vate sector efforts to take an existing product into de-veloping countries with organizations that are tryingto develop a new product category, such asmicrobicides? Is it useful to look at single candidateproduct development efforts in addition to broaderportfolio approaches? There may be good reasons totreat such a broad group as one category if there areuseful areas of collaboration or lessons between thesedifferent areas. However, doing so also runs the risk ofincreasing confusion rather than clarifying the field.

Second, as PD PPPs move from an experimental toa more established phase, there is a clear opportunityfor greater coordination both within and across PDPPPs to ensure that best practices are shared, money isspent in the most efficient way and the platforms thathave been built by one PD PPP and could be sharedwith others are known and leveraged. Collaborationin specific targeted areas may make sense across do-nors, within and across diseases and across product areasfor a disease. There are a number of informal collabo-rations and discussions taking place today, but a moresystematic approach could be beneficial.

Third, it is important to look at the expertise beingcalled upon and places where gaps still exist. If PDPPPs are going to succeed as a whole, two groups mayneed to be consistently brought into the discussion:private sector R&D experts and developing countryclinicians and stakeholders. The expertise of the com-mercial pharmaceutical industry is essential, but notnecessarily easy to recruit as industry’s motivation islargely focused on making a profit. As Table 9 shows,the private sector, which holds much of the knowl-edge about how to turn basic research into appliedresearch into products, is participating in some PDPPPs but not to any consistent degree. A lone indi-


1 2 0

vidual on a board (particularly if retired) is not enoughto transfer expertise.1 The question of private sectorparticipation, where it has occurred and where it hasnot, is important and worthy of its own investigation.

Similarly, there is a real potential risk in any R&Dprocess that a good product will be developed but notmatched to the needs of the end users. The obstaclesto getting a useful product to the end user include,among others, regulatory, procurement, distribution,infrastructure, manufacturing and utilization hurdles.It is important that knowledgeable end users bebrought into the process from the relevant locationsat the earliest possible time and given an active voicein the process. These conversations also should includeregulatory gatekeepers and technical advisors like WHOand National Health Officials who often influence whatlocal health authorities regard as feasible. The scien-tific hurdles in developing a product are only half ofthe battle. Figuring out how these new tools can bedeployed in countries facing extreme financial and in-frastructure challenges is the other.

In closing, it is important to applaud the efforts ofthe many individuals who have carried the PD PPPfield to this point. These include donors, researchers,advocates, pioneers, academics and clinicians. Manywho have embarked on this experiment have changedcareer paths or switched from secure jobs in labs orcompanies to place themselves on the front lines of anevolving field. The early signs are exciting. Now is thetime to define both the field and its requirements tocreate a powerful array of new tools for combating thegreatest killers on the planet.

APPENDIX

This appendix consists of one-page overviews of eachof the 17 product development partnerships aroundwhich the 15–16 April 2004 IPPPH meeting was for-mulated.

These summary sheets were completed by the prod-uct development partnerships themselves around thetime of the meeting with the aid of the guidance anddefinitions outlined below:

Guidance and definitions“These one-page summary sheets are an initial attemptto collect information on the 17 PD PPPs invited to the15–16 April 2004 gathering at Wellcome Trust. The ob-jective of these sheets is to give participants [and readers]a quick way to understand who is targeting which dis-eases and products, and how far along they are in theirefforts.”

Relative contributionThis section is meant to capture the relative expertise andcapital that have been contributed by different sectors:

• Public includes the government, multilateral insti-tutions, public academic institutions, or governmentlabs.

• Private includes for-profit businesses (including butnot limited to pharma and biotech companies), forprofit laboratories, and the not-for-profit foundationsestablished by the major pharmaceutical companies.

• Donor or Foundation includes all non-profit andcharitable enterprises excluding government donors(who are classified under public) and pharmaceuti-cal foundations (who are included in private to cap-ture activities of the pharmaceutical companies).

• The amount of capital contributed counts all fundscommitted. It should not include in-kind contribu-tions.

• The amount of in-kind contribution is an estimate ofthe in-kind/non-financial contributions that partnershave contributed in terms of expertise, infrastructure,and compounds. We count as in-kind contributionsthose from corporations paid for a service/product atbelow market value, where this can be documented.

• R&D model processes is a subjective rating to capturethe influence from each of the sectors on the R&Dmodel employed by the PD PPP.

1 The issue of ensuring real collaboration of the private sector isoften discussed as a problem but is not taken up at a levelrequired to change the dynamic. While some individuals andcompanies from the private sector have chosen to participate,others find the PD PPP field confusing and state that researchis “not being done in a rigorous enough way to succeed”. Stillothers are willing to collaborate but not on terms acceptableto PD PPPs.

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Scope of activitiesThis section compares the scope of current activities andactivities planned for the future. For each activity nowbeing done or planned, the question is whether it is doneprimarily through in-house staff or mostly out-sourcedthrough contracts to a third party, even if generallyoverseen by in-house staff.

Portfolio strategyThis section asks for the number of products today andforecast for the end of 2005 in the portfolio. It should notinclude compounds that others in the field are testing forthe same disease where there is no support from your or-ganization.

Size/ManagementThis asks for a summary of the staff size, governance andadvisory structures:

• Total staff excluding secretarial support.• Capital raised to date, excluding in-kind contribu-

tions.• Number of donors contributing funds.• Size of various bodies, where relevant.

Published materialsThis examines whether the organization has adopted cer-tain types of business practice through identifying pub-lished materials available to the public and donors:

• A scientific blueprint examines the state of the sciencetoday and develops a plan, often a portfolio plan, forwhere and how to invest to get to an end product. Itusually includes what is known and not yet known in

the basic science and a list of those involved in researchand development.

• A business plan describes the strategy and organiza-tion structure required to meet a mission. It spells outthe financial requirements and begins to address ba-sic questions about the approach required to meet themission.

• A pharmaco-economic report looks at the market de-mand for a given product, the epidemiology and thegeographic areas in which a need exists. It includeseconomic forecasting about the size of this potentialmarket if a product were available.

• An access plan lays out a strategy for how to get theproduct in the hands of those who need it. It can in-clude a distribution strategy for the relevant areas,patient groups and given the existing health care in-frastructure. It can include groups that need to beinvolved in distribution, and a plan for developingthe needed financial mechanisms so the product canbe procured, among other issues.

• An advocacy/education plan lays out a strategy toincrease public awareness and/or change public policyat the key levels. It may involve a study of relevantpolicy makers, opinions, regulations/legislations, andpoints of influence among other factors.

List of in-kind contributorsThis section lists anyone providing any ‘in-kind’ contri-butions, with their type of contribution and assessment offinancial value, where available.

The summary sheets that follow represent the responsesof individual PD PPPs as supplied in mid-2004.



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Aeras Global TB Vaccine Foundation Director: Dr. Jerald SadoffLaunch date: 1997 Address: Aeras Global TB Vaccine FoundationFocus: Develop & distribute vaccines 7500 Georgetown Road, #800Target: TB Bethesda, MD 20814Website: www.aeras.org USA

MISSION

The Aeras Global TB Vaccine Foundation (formerly known as the Sequella Global Tuberculosis Foundation) was founded in 1997 to help develop new conceptsand tools to control the global TB epidemic.

RELATIVE CONTRIBUTION

Total size Percent public Percent private Donor/foundation/(%) (%) other (%)

Background of Management Team 9 22 44 33Background of board 8 28 57 14Amount of capital contributed $107.9m 2 — 98Amount of in-kind contribution (est) — — — —R&D model/processes (est) — — 100 —

SCOPE OF ACTIVITIES

Today Future (2005+) Activity managed

Yes/No Yes/No In-house Out-sourced

Research Y Y Y YPre-clinical Y Y Y YPhase I testing Y Y Y YPhase II testing Y Y Y YPhase III testing Y Y Y YRegulatory approval Y Y Y xxxManufacturing Y Y Y YDistribution/‘access’ Y/N Y/N Y YAdvocacy/education Y Y Y Y

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) 6 Forecast end 2005 portfolio (# of pdts): 6• Pre-clinical: 4 • Pre-clinical: —• Phase I: 2 • Phase I: —• Phase II: — • Phase II: 4• Phase III: — • Phase III: 2• In-market: — • In-market: —Number of clinical trials: — Number of clinical trials: 10Location of clinical trials: S. Africa, USA, Europe Location of clinical trials: S.Africa, USA, Europe

SIZE/MANAGEMENT PUBLISHED MATERIALS

Number of professional employees: 64 Use of:Capital raised to date: $107.9m • Scientific blueprint YNumber of donors: 1 • Business plan YBoard of Directors size: 7 • Pharmaco-economic report YScientific Advisory Committee size (if used): 6 • Access plan YPolicy Advisory Committee size (if used): — • Advocacy plan N

LIST OF PARTNERS

Contribution type In-kind contribution financial value

Bill & Melinda Gates Foundation $107.9mNIH $20mEDCTP (projected) $20mUS AID (projected) $25mECE (projected) $25m

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Drugs for Neglected Diseases Initiative (DNDi) Executive Director: Dr. Bernard PecoulLaunch date: July 2003 Address: 1 Place St. GervaisFocus: Drug R&D Geneva 1201Target: Sleeping sickness, leishmaniasis & chagas SwitzerlandWebsite: www.dndi.org

MISSION

DNDi will improve the health and quality of life for people suffering from neglected diseases by using an alternative model to develop drugs for these diseases andensuring equitable access to new and field-relevant health tools. It will also build public responsibility and leadership in addressing the needs of these patients. DNDiwill achieve its goals by building an R&D project portfolio, raising awareness about the crisis in lack of drugs for neglected diseases, and by using and strengtheningexisting R&D capacity in disease-endemic countries.



Background of Management Team* (6/2004) 18 13 50 37Background of Board 10 60 30 10Amount of capital committed** $30m — — 100Amount of in-kind contribution (est) Yes — — —R&D model/processes (est) xxx xxx xxx xxx

SCOPE OF ACTIVITIES



Research Y Y N YPre-clinical Y Y N YPhase I testing Y Y N YPhase II testing Y Y N YPhase III testing Y Y N YRegulatory approval Y Y Y YManufacturing N N Y NDistribution/‘access’ N N Y NAdvocacy/education Y Y Y N

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) 9 Forecast end 2005 portfolio (# of pdts): xxx• Discovery 4• Pre-clinical: 1 • Pre-clinical: xxx• Phase I: — • Phase I: xxx• Phase II: — • Phase II: xxx• Phase III: 4 • Phase III: xxx• In-market: — • In-market: xxxNumber of clinical trials: 1 Number of clinical trials: xxxLocation of clinical trials: Burkina Faso Location of clinical trials: xxx


Number of professional employees: 8 Use of:Capital raised to date: $30m • Scientific blueprint —Number of donors: 1** • Business plan YBoard of Directors size: 10 • Pharmaco-economic report —Scientific Advisory Committee size (if used): 15 • Access plan —Policy Advisory Committee size (if used): xxx • Advocacy plan xxx

LIST OF PARTNERS


Indian Council of Medical Research xxxInstitut PasteurKenya Medical Research InstituteMinistry of Health, MalaysiaMédecins Sans FrontièresOswaldo Cruz FoundationWHO/TDR

* Plus 10 consultants** MSF committed to maximum support of $30m over 5 years.

Does not include $2.6m budgeted for FACT malaria project



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The European Malaria Vaccine Initiative (EMVI) Director: Dr. Soren JepsenLaunch date: 1998 Address: Statens Serum InstitutFocus: Vaccines Artillerivej 5, 2300 Copenhagen STarget: Malaria DanmarkWebsite: www.emvi.org

MISSION

Contribute to global efforts to control malaria by:• providing a mechanism for accelerated development and clinical trials of malaria vaccines in Europe and developing countries• promoting affordability and accessibility of malaria vaccines in developing countries



Background of Management Team 3 100 — —Background of Board 10 90 10 —Amount of capital contributed $18m* 100 — —Amount of in-kind contribution (est) 0 — — —Ownership over Pdts produced (est) — 100 — —R&D model/processes (est) xxx xxx xxx xxx

SCOPE OF ACTIVITIES



Research N N N YPre-clinical Y Y N YPhase I testing Y Y N YPhase II testing Y Y N YPhase III testing N N N YRegulatory approval xxx xxx xxx xxxManufacturing N N N YDistribution/‘access’ N N N YAdvocacy Y Y Y N

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) 10 Forecast end 2005 portfolio (# of pdts): 11• Pre-clinical: 4 • Pre-clinical: 5• Phase I: 4–5 • Phase I: 4• Phase II: 0 • Phase II: 1• Phase III: 0 • Phase III: 0• In-market: 0 • In-market: 0Number of clinical trials: 3 Number of clinical trials: 4Location of clinical trials: Switzerland, UK, India,The Netherlands, Burkina Faso Location of clinical trials: xxx


Number of professional employees: 3 Use of:Capital raised to date: $18m* • Scientific blueprint YNumber of donors: 6** • Business plan YBoard of Directors size: 10 • Pharmaco-economic report NScientific Advisory Committee size (if used): 7 • Access plan NPolicy Advisory Committee size (if used): xxx • Advocacy plan ?

LIST OF PARTNERS


xxx xxx

* = 15 million Euros** Donors include DANIDA/DK, DGIS/NL, Sida/SAREC/SE, DCI/IR, EC/BE,CIH/NO

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Foundation for Innovative New Diagnostics (FIND) Director: Dr. Giorgio RoscignoLaunch date: 2003 Address: 71, av Louis-CasaiFocus: Develop diagnostics Case postale 93Target: TB Initially 1216 Cointrin/GenevaWebsite: www.finddiagnostics.org Switzerland

MISSION

FIND will accelerate the development, evaluation and appropriate use of high-quality yet affordable diagnostic tools for infectious diseases in developing countries.



Background of Management Team 6 50 50 —Background of Board 4 25 50 25Amount of capital contributed $30m — — 100Amount of in-kind contribution (est) — — — —R&D model/processes (est) — 30 70 —

SCOPE OF ACTIVITIES



Basic research N N — YPre-clinical Y N — YPhase I testing Y N — YPhase II testing Y N — YPhase III testing Y N — YRegulatory approval Y Y — YManufacturing N Y — YDistribution/‘access’ N Y — YAdvocacy/education N Y — Y

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) 5 Forecast end 2005 portfolio (# of pdts): 12• Pre-clinical: 1 • Pre-clinical: 5• Phase I: 1 • Phase I: 1• Phase II: 1 • Phase II: 2• Phase III: 2 • Phase III: 3• In-market: — • In-market: 1Number of clinical trials: 3 Number of clinical trials: 6Location of clinical trials: Africa, Latin America, Asia Location of clinical trials: Africa, Asia, USA, E.Europe


Number of professional employees: 7 Use of:Capital raised to date: $30m • Scientific blueprint YNumber of donors: 1 (Gates) • Business plan YBoard of Directors size: 5 • Pharmaco-economic report YScientific Advisory Committee size (if used): 8 • Access plan in processPolicy Advisory Committee size (if used): 4 • Advocacy plan —

LIST OF PARTNERS


Stop TB PartnershipBiotechnology Companies (North, South) Discussions ongoingMajor Diagnostic Companies Discussions ongoingPublic Research Institutes (North, South) Discussions ongoingMerck Germany Lump sum purchase patents n/aGovernment Institutions Discussions ongoing



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Global Microbicide Project (GMP) Director: Dr. Michael J.K. HarperLaunch date: 2000 Address: CONRADFocus: Microbicides 1611 N. Kent St., Suite 806Target: STI, HIV/AIDS Arlington, VA 22209-2111Website: www.gmp.org USA

MISSION

To develop vaginal methods that will protect women against sexually transmitted infections, including HIV/AIDS.



Background of Management Team 6 100 0 0Background of Board 10 83 17 0Amount of capital contributed $64m* 45 5 50Amount of in-kind contribution (est) $3m 4 96 —R&D model/processes (est) Yes — — —

SCOPE OF ACTIVITIES



Research Y Y Y YPre-clinical Y Y Y YPhase I testing Y Y Y YPhase II testing Y Y N YPhase III testing Y Y N YRegulatory approval Y Y Y YManufacturing Y Y N YDistribution/‘access’ N N N YAdvocacy Y Y N Y

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) 16 Forecast end 2005 portfolio (# of pdts): 12• Pre-clinical: 8 • Pre-clinical: 4• Phase I: 7 • Phase I: 7• Phase II: 0 • Phase II: 0• Phase III: 1 • Phase III: 2• In-market: 0 • In-market: 0Number of clinical trials: 9 Number of clinical trials: 9Location of clinical trials: 5 countries Location of clinical trials: 9 countries


Number of professional employees: 14 Use of:Capital raised to date: $64m* • Scientific blueprint YNumber of donors: 9* • Business plan YBoard of Directors size: Strategic Advisory Board 10 • Pharmaco-economic report NScientific Advisory Committee size (if used): 12 • Access plan YPolicy Advisory Committee size (if used): n/a • Advocacy plan N

LIST OF PARTNERS


Partners: ITM, WHO, FHI, Biosyn, Indevus, MedTech, OSEL, Cash and in kind $3mPATH, Personal Care Products, Polydex Pharm., ReProtect

* Includes funds awarded to CONRAD (GMP parent) by USAID, CDC, and NIH for microbicide research

1 2 7

Global Alliance for TB Drug Development Director: Dr. Maria FreireLaunch date: 2000 Address: 80 Broad Street, 31st FloorFocus: Develop drugs New York, NY 10004Target: TB USAWebsite: www.tballiance.org

MISSION

To accelerate the discovery and/or development of affordable new TB drugs that will:• Shorten the duration of TB treatment or otherwise simplify its completion• Improve the treatment of latent TB infection• Be effective against multi-drug resistant TB (MDR-TB)



Background of Management Team 8 50 50 —Background of Board 11 50 40 10Amount of capital contributed $42.2m 4.7 0.3 94.9Amount of in-kind contribution (est) $1.6m 80 6 14R&D model/processes (est) — 10 85 5

SCOPE OF ACTIVITIES



Basic research N N N NPre-clinical Y Y N YPhase I testing N Y N YPhase II testing Y Y N YPhase III testing N N N YRegulatory approval Y Y Y YManufacturing N N N Y/NDistribution/‘access’ N Y N Y/NAdvocacy Y Y Y Y

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) 10 Forecast end 2005 portfolio (# of pdts):• Pre-clinical: 9 • Pre-clinical: 12• Phase I: 0 • Phase I: 2• Phase II: 1 • Phase II: 1• Phase III: 0 • Phase III: 0• In-market: 0 • In-market: 0Number of clinical trials: n/a Number of clinical trials:Location of clinical trials: Africa, Asia, South America Location of clinical trials: Africa, Asia, South America


Number of professional employees: 14 Use of:Capital raised to date: $42.2m • Scientific blueprint YNumber of donors: 5 • Business plan YBoard of Directors size: 10 • Pharmaco-economic report YScientific Advisory Committee size (if used): 14 • Access plan xxPolicy Advisory Committee size (if used): 30 • Advocacy plan xx

LIST OF PARTNERS


Gates & Rockefeller Foundations Funding $25m/$15m = $40m (grants)Dutch Ministry of Development Cooperation/WHO Funding $2m in (grant)NIAID Pre-clinical capacity and in-kind funding $1.5m (in kind)GSK Seconded expertise $0.1m (in-kind)CDC & TBTC, IUATLD, MRC South Africa Clinical Trials & Scientific Networking n/aResearch Triangle Institute Expertise n/aBristol Myers Squibb Foundation/other donors Funding $0.2m (grant and donations)



1 2 8

Human Hookworm Vaccine Initiative (HHVI) Director: Peter Hotez MD PhDLaunch date: 2000 Address: Hosted by Albert SabinFocus: Vaccines Vaccine InstituteTarget: Hookworm 161 Cherry StreetWebsite: www.sabin.org New Canaan, CT 06840-4818

MISSION

The Human Hookworm Vaccine Initiative (HHVI) is developing a multi-antigen Human Hookworm Vaccine comprised of both third-stage infective larval (L3)and adult-stage antigens of human hookworms. The first antigen component of this vaccine is the Na-ASP-2 Hookworm Vaccine, comprised of a single recombinantprotein from Necator americanus L3. The intended use of the Na-ASP-2 Hookworm Vaccine is induction of a measurable antibody response and, when given toindividuals at risk for hookworm infection confer protection or partial protection of these individuals from infection or re-infection with hookworm. This wouldreduce worm burden and its concomitant outcomes, hookworm anemia and disease.



Background of Management Team 4 10 50 40Background of Board* 12 25 75 —Amount of capital contributed $20m 5 — 95Amount of in-kind contribution (est) 4 10 60 30R&D model/processes (est) 1 5 5 90

SCOPE OF ACTIVITIES



Research Y Y Y NPre-clinical Y Y Y YPhase I testing N Y Y NPhase II testing N Y Y YPhase III testing N Y Y YRegulatory approval Y Y Y YManufacturing Y Y Y YDistribution/‘access’ N Y — —Advocacy/education Y Y Y Y

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) 6 Forecast end 2005 portfolio (# of pdts): 6• Pre-clinical: 6 • Pre-clinical: 5• Phase I: — • Phase I: 2• Phase II: — • Phase II: —• Phase III: — • Phase III: —• In-market: — • In-market: —Number of clinical trials: — Number of clinical trials: 2Location of clinical trials: Location of clinical trials: USA, Brazil


Number of professional employees: 30 Use of:Capital raised to date: $20m • Scientific blueprint 1Number of donors: 4 • Business plan —Board of Directors size:* 12 • Pharmaco-economic report —Scientific Advisory Committee size: 7 • Access plan —Policy Advisory Committee size (if used): — • Advocacy plan —

LIST OF PARTNERS


George Washington University, Washington, DCFIOCRUZ, Brazil Research, Product DevelopmentLondon School of Hygiene and Tropical Medicine, UK and Clinical TestingQueensland Institute for Medical Research, Australia

* Sabin Board/SAC

1 2 9

International AIDS Vaccine Initiative Director: Dr. Seth BerkleyLaunch date: 1996 Address: 110 William Street, floor 27Focus: Vaccines NY, NY 10038-3901 USATarget: HIV/AIDS Regional offices in Amsterdam,Website: www.iavi.org Nairobi and New Delhi

MISSION

To ensure the development of safe effective accessible preventive HIV vaccines for use throughout the world



Background of Management Team 11 27 73 —Background of Board 17 53 47 —Amount of capital contributed $350m 45 10 45Amount of in-kind contribution (est) $20m xxx 100 xxxR&D model/processes (est) xxx xxx xxx xxx

SCOPE OF ACTIVITIES



Research Y Y Y YPre-clinical Y Y Y YPhase I testing Y Y Y YPhase II testing Y Y Y YPhase III testing N Y N YRegulatory approval Y Y Y XManufacturing Y Y N YDistribution/‘access’ Y N Y YAdvocacy/education Y Y — Y

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) Forecast end 2005 portfolio (# of pdts):• Pre-clinical: 20 • Pre-clinical: 20• Phase I: 5 • Phase I: 10• Phase II: 1 • Phase II: 2• Phase III: 0 • Phase III: 1• In-market: 0 • In-market: 0Number of clinical trials: 15 Number of clinical trials: 20Location of clinical trials: Belgium, Germany, Kenya, South Africa, Location of clinical trials: North America, Europe, India, Africa, China

Switzerland, Uganda, UK, UAS


Number of professional employees: 125 Use of:Capital raised to date: $350m • Scientific blueprint YNumber of donors: 50 • Business plan YBoard of Directors size: 17 • Pharmaco-economic report YScientific Advisory Committee size: 12 • Access plan YPolicy Advisory Committee size: 16 • Advocacy plan Y

LIST OF PARTNERS


More than 50 partners operating in 23 countries (see web site) All types Too numerous to count



1 3 0

Institute for OneWorld Health CEO & Founder: Dr. Victoria HaleLaunch date: 2000 Address: 580 California StFocus: Drugs and vaccines Suite 900Target: Initially Leishmaniasis (India) and Chagas (LA) San Francisco, CA 94104Website: www.oneworldhealth.org

MISSION

Develop safe, effective, and affordable, new medicines for people afflicted with infectious diseases in the developing world. Target infectious diseases in the devel-oping world that lack adequate therapies such as leishmaniasis, Chagas disease, diarrheal diseases, schistosomiasis and malaria.



Background of Management Team 4 25 75 —Background of Board 6 17 67 17Amount of capital contributed $11.3m — — 100Amount of in-kind contribution (est) $4.5m 33 67 —R&D model/processes (est) — — — —

SCOPE OF ACTIVITIES



Research N N N NPre-clinical Y Y N YPhase I testing Y Y Y NPhase II testing Y Y Y NPhase III testing Y Y Y NRegulatory approval Y Y Y NManufacturing Y Y N YDistribution/‘access’ N Y Y NAdvocacy/education Y Y Y N

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) 5 Forecast end 2005 portfolio (# of pdts): 8• Pre-clinical: 3 • Pre-clinical: 6• Phase I: 0 • Phase I: 1• Phase II: 1 • Phase II: 0• Phase III: 1 • Phase III: 1• In-market: — • In-market: 1Number of clinical trials: 2 Number of clinical trials: (+ Ph IV) 5Location of clinical trials: India Location of clinical trials: Asia


Number of professional employees: 25 Use of:Capital raised to date: $11.3m • Scientific blueprint YNumber of donors: 3 • Business plan NBoard of Directors size: 6 • Pharmaco-economic report NScientific Advisory Committee size (if used): 16 • Access plan NPolicy Advisory Committee size (if used): — • Advocacy plan N

LIST OF PARTNERS


Celera Genomics Develop CRA-3316 for Chagas Not disclosedNIH Preclinical testing $1.5mTDR/WHO Paromomycin collaboration Not disclosedWalter Reed Army Institute of Research Consulting Not disclosedUC Santa Barbara Patent donation for schistosomiasis Not disclosedYale/University of Washington Develop azoles for Chagas Not disclosed

1 3 1

International Partnership for Microbicides (IPM) Director: Dr. Zeda F. RosenbergLaunch date: 2002 Address: 1010 Wayne Avenue, Suite 1450Focus: Pdt to reduce trans of HIV/other pathogens Silver Spring, MD 20910Target: HIV/AIDS USAWebsite: www.ipm-microbicides.org

MISSION

To accelerate the discovery, development and accessibility of safe and effective microbicides to prevent transmission of HIV for women in developing countries.IPM was established to identify and address gaps or bottlenecks that may limit the development, clinical testing, approval, distribution, and use of microbicides.



Background of Management Team 6 50 50 —Background of Board 10 70 30 —Amount of capital contributed $94.5m 21 — 79Amount of in-kind contribution (est) 250k — 100 —R&D model/processes (est) — 10 90 —

SCOPE OF ACTIVITIES



Research Y Y Y YPre-clinical Y Y Y YPhase I testing Y Y Y YPhase II testing N Y Y YPhase III testing N Y Y YRegulatory approval Y Y Y YManufacturing N Y Y YDistribution/‘access’ N N N YAdvocacy/education Y Y Y Y

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) 3 Forecast end 2005 portfolio (# of pdts): 6• Pre-clinical: 3 • Pre-clinical: 5• Phase I: 1–2 • Phase I: 3• Phase II: 0 • Phase II: 1• Phase III: 0 • Phase III: 0• In-market: 0 • In-market: 0Number of clinical trials: 1 Number of clinical trials: 4Location of clinical trials: Belgium, UK Location of clinical trials: International


Number of professional employees: 8 Use of:Capital raised to date: $94m • Scientific blueprint YNumber of donors: 9 • IPM business plan YBoard of Directors size: 10 • Pharmaco-economic report (Rockefeller Reports) YScientific Advisory Committee size (if used): 10 • Access plan (Rockefeller Reports) YPolicy Advisory Committee size (if used): 10 • Advocacy plan (Rockefeller Reports) Y

LIST OF PARTNERS


Tibotec/Johnson & Johnson Phase I trial support $250,000



1 3 2

Microbicides Development Programme (MDP) Director: Profs. Jonathan Weber/Janet Darbyshire,Launch date: 2001 Address: c/o Imperial College Winston Churchill Wing,Focus: Pdt to reduce transmission of HIV/AIDS Faculty of Medicine, St Mary’s Campus,Target: Norfolk Place, London W2 1PGWebsite: www.mdp.mrc.ac.uk

MISSION

The MDP aims to evaluate potential microbicides in vitro, to carry out safety studies in the UK and Africa, to conduct social science research into acceptability andbarriers to uptake of products, complete phase III effectiveness trials and to facilitate marketing and access to a successful microbicide.



Background of Management Team 8 100 — —Background of Board 21 100 — —Amount of capital contributed $27m 100 — —Amount of in-kind contribution (est) Yes — — —R&D model/processes (est) Yes — — —

SCOPE OF ACTIVITIES



Research Y Y Y NPre-clinical Y Y Y NPhase I testing Y Y Y NPhase II testing Y Y Y NPhase III testing N Y Y NRegulatory approval N N — —Manufacturing N N N YDistribution/‘access’ N N N YAdvocacy/education N N N Y

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) 3 Forecast end 2005 portfolio (# of pdts): 2• Pre-clinical: — • Pre-clinical: —• Phase I: 1 • Phase I: —• Phase II: 1 • Phase II: —• Phase III: — • Phase III: 2• In-market: — • In-market: —Number of clinical trials: 2 Number of clinical trials: 1Location of clinical trials: UK, Uganda Location of clinical trials: S. Africa, Zambia, Uganda, Tanzania, Cameroon,

Swaziland


Number of professional employees: 200 Use of:Capital raised to date: $27m • Scientific blueprint NNumber of donors: 1 • Business plan NBoard of Directors size: 21 • Pharmaco-economic report NScientific Advisory Committee size (if used): 8 • Access plan NPolicy Advisory Committee size (if used): No • Advocacy plan N

LIST OF PARTNERS


UK Dept. for Intl. Development $27mIndevus Gel (?)ML Laboratories Gel (?)Dow Pharmaceuticals/NY Blood Center Gel (?)

1 3 3

Medicines for Malaria Venture (MMV) Director: Dr. Chris HentschelLaunch date: 1999 Address: PO Box 1826Focus: Drugs 20, rte de Pré-Bois,Target: Malaria 1215 Geneva 15Website: www.mmv.org Switzerland

MISSION

To bring public, private and philanthropic sector partners together to fund and manage the discovery, development and registration of new medicines for thetreatment and prevention of malaria in disease-endemic countries.Goal: one new drug every five years with a first one by 2010.



Background of Management Team 11 — 100 —Background of Board 9 22 66 11Amount of capital contributed $107m 30.1 1 68.9Amount of in-kind contribution (est) $25m 2 98 —R&D model/processes (est) — — 100 —

SCOPE OF ACTIVITIES


Yes/No Yes/No In-house* Out-sourced

Research Y Y N YPre-clinical Y Y N YPhase I testing Y Y N YPhase II testing Y Y N YPhase III testing Y Y N YRegulatory approval Y Y N YManufacturing Y Y N YDistribution/‘access’ Y Y N YAdvocacy/education Y Y Y Y

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) 21 Forecast end 2005 portfolio (# of pdts): xxx• Pre-clinical: 6 • Pre-clinical: 3• Phase I: 3 • Phase I: 5• Phase II: 1 • Phase II: 7• Phase III: 2 • Phase III: 5• In-market: xxx • In-market: 1Number of clinical trials: 7 Number of clinical trials: 17Location of clinical trials: Africa, Asia, Europe Location of clinical trials: Africa, Asia, Latin America


Number of professional employees: 11 Use of:Capital raised to date: $107m • Scientific blueprint N2003 Annual Budget: $19.2m • Business plan/update YNumber of donors: 11 • Pharmaco-economic report NBoard of Directors size: 9 • Access plan NScientific Advisory Committee size (if used): 11 • Advocacy plan NPolicy Advisory Committee size (if used): No

LIST OF PARTNERS


Roche, Novartis, Ranbaxy, Shin Poong Pharma Co, Bayer, Various in-kind $25mImmtech, Jacobus Pharma USA, Paratek Pharma,GSK-Tres Cantos, GSK-UK, GSK-USA, Holleykin Pharma/China


* MMV staff closely supervise/monitor work of contractors/collaborators.


1 3 4

Malaria Vaccine Initiative (MVI) Director: Melinda MoreeLaunch date: 1999 Address: 1455 NW Leary WayFocus: Vaccines Seattle, WA 98107Target: Malaria USAWebsite: www.malariavaccine.org

MISSION

MVI’s mission is to accelerate the development of promising malaria vaccines and ensure their availability and accessibility in the developing world.



Background of Management Team 5 20 40 40Background of Board n/a n/a n/a n/aAmount of capital contributed $150m 0 <1 >99Amount of in-kind contribution (est) Not quantified — — —R&D model/processes (est) — 20 80 —

SCOPE OF ACTIVITIES



Research N N — —Pre-clinical Y Y N YPhase I testing Y Y N YPhase II testing (pilot efficacy) Y Y N YPhase III testing (registration trial) N Y N YRegulatory approval Y Y Y YManufacturing — — — YDistribution/‘access’ Y Y Y YAdvocacy/education Y Y Y Y

PORTFOLIO STRATEGY

January 2004 portfolio (# of vaccine concepts) 15 January 2005 portfolio (# of vaccine concepts): 18• Pre-clinical: 9 • Pre-clinical: 10• Phase I: 3 • Phase I: 4• Phase II: (pilot efficacy) 3 • Phase II: (pilot efficacy) 4• Phase III: (registration trial) 0 • Phase III: (registration trial) 0• In-market: 0 • In-market: 0Number of clinical trials: 7 Number of clinical trials: 10Location of clinical trials: Europe, USA, Africa Location of clinical trials: Europe, USA, Africa


Number of professional employees: 16 Use of:Capital raised to date: $150m • Scientific blueprint YNumber of donors: 2 • Business plan YBoard of Directors size: — • Pharmaco-economic report due 2005Scientific Advisory Committee size (if used): varies • Access plan —Policy Advisory Committee size (if used): — • Advocacy plan Y

LIST OF PARTNERS


All of MVI’s partners and collaborators (academic, government, industry, non-profit) contribute resources to the projects. These in-kind contributions have notbeen quantified.

1 3 5

Pediatric Dengue Vaccine Initiative (PDVI) Director: Dr. Scott HalsteadLaunch date: 2002 Address: International Vaccine InstituteFocus: Vaccines Kwanak-gu Seoul POB 14Target: Pediatric dengue Republic of KoreaWebsite: www.pdvi.org

MISSION

PDVI will raise awareness and work with public and private partners in the North and the South to accelerate the development and introduction of a dengue vaccinethat is safe, accessible and affordable to poor children in endemic countries. PDVI is designed to augment and supplement efforts of the private sector in denguevaccine testing for efficacy and safety.



Background of Management Team 4 75 0 25Background of Board 9 89 11 —Amount of capital contributed $56m 0.5 0.5 99Amount of in-kind contribution (est) — — — —R&D model/processes (est) $250 65 35 0

SCOPE OF ACTIVITIES



Research Y Y — YPre-clinical Y Y — YPhase I testing N Y — YPhase II testing N Y — YPhase III testing N Y — YRegulatory approval — — — —Manufacturing N N — —Distribution/‘access’ N N — —Advocacy/education Y Y Y —

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) 0* Forecast end 2005 portfolio (# of pdts): 0*• Pre-clinical: — • Pre-clinical: —• Phase I: — • Phase I: —• Phase II: — • Phase II: —• Phase III: — • Phase III: —• In-market: — • In-market: —Number of clinical trials: — Number of clinical trials: 1Location of clinical trials: — Location of clinical trials: xxx


Number of professional employees: 4 Use of:Capital raised to date: $56m • Scientific blueprint NNumber of donors: 10* • Business plan YBoard of Directors size: 9 • Pharmaco-economic report YScientific Advisory Committee size: 13 • Access plan NPolicy Advisory Committee size: — • Advocacy plan N

* Mature field with several private sector companies developing dengue vaccines de novo or those invented in the public sector. PDVI’s strategy is to get ahead ofdevelopment funding and prepare Phase III trial sites to be made available at reduced cost to manufacturers specifically for pediatric testing.

** Funders include Gates ($55m), Rockefeller, Aventis Pasteur, GSK, Acambis, Novartis, Ellison, the US Navy, the US Army, Jackson Foundation



1 3 6

PneumoADIP Executive Director: Dr. Orin LevineLaunch date: 2003 Address: Johns Hopkins UniversityFocus: Vaccines Bloomberg School of Public HealthTarget: Pneumonia and meningitis Baltimore, MD 21205-2179Website: www.preventpneumo.org USA

MISSION

Our mission is to improve child survival and health by accelerating the evaluation of and access to, new life saving pneumococcal vaccines for the world’s children.



Background of Management Team 7 71 29 —Background of Board* xxx xxx xxx xxxAmount of capital contributed $30m — — 100Amount of in-kind contribution (est)** 100,000 50 50 —R&D model/processes (est) xxx xxx xxx xxx

SCOPE OF ACTIVITIES



Research Y Y Y YPre-clinical/surveillance activities Y Y N YPhase I testing N N N YPhase II testing N Y — —Phase III testing N Y — —Regulatory approval Y Y N YManufacturing N N — —Sales/distribution N N — —Advocacy/education Y Y Y Y

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) *** — Forecast end 2005 portfolio (# of pdts): —• Pre-clinical: — • Pre-clinical: —• Phase I: — • Phase I: —• Phase II: — • Phase II: —• Phase III: — • Phase III: 2• In-market: — • In-market: —Number of clinical trials:*** — Number of clinical trials: (2006)Location of clinical trials: — Location of clinical trials: —


Number of professional employees: 7 Use of:*****Capital raised to date: $30m • Scientific blueprint YNumber of donors: 1 (GAVI) • Business plan —Board of Directors size:* 7 • Pharmaco-economic report YScientific Advisory Committee size:**** xxx • Access plan —Policy Advisory Committee size (if used): 6 • Advocacy Plan Y

LIST OF PARTNERS


WHO xxx xxx

* Management committee sub-group of GAVI Board. Meets twice a year.** Logo development and other communications support*** Active phase III trials in Gambia and Philippines and S.Africa by 2 private sector companies**** No standing committee; expert panel is convened as needed***** Developing communications plan and economic report

1 3 7

Rotavirus Vaccine Accel Devel & Intro Plan (Rota-ADIP) Director: John Wecker, Ph.D.Launch date: 2003 Address: Rotavirus Vaccine Program,Focus: Vaccines 1455 NW Leary Way, Seattle, WA 98107Target: Rotavirus USAWebsite: www.rotavirusvaccine.org

MISSION

To reduce child morbidity and mortality from diarrheal disease by accelerating the availability of rotavirus vaccines appropriate for use in developing countries.



Background of Management Team 6 83 17 —Background of Board* 6 83 17 —Amount of capital contributed $30m — — 100Amount of in-kind contribution (est) xxx — — —R&D model/processes (est) — 50 100 —

SCOPE OF ACTIVITIES



Research N N — —Pre-clinical N N — —Phase I testing N N — —Phase II testing N Y N YPhase III testing N Y N YRegulatory approval xx xx xx xxManufacturing N N — —Distribution/‘access’ N Y Y —Advocacy/education Y Y Y N

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) 2 Forecast end 2005 portfolio (# of pdts): 2• Pre-clinical: — • Pre-clinical: —• Phase I: — • Phase I: —• Phase II: 2 • Phase II: —• Phase III: — • Phase III: 2• In-market: — • In-market: —Number of clinical trials: — Number of clinical trials: 4Location of clinical trials: Location of clinical trials: Africa, Asia


Number of professional employees: 6 Use of:Capital raised to date: $30m • Scientific blueprint NNumber of donors: 1 • Business plan NBoard of Directors size: 6 • Pharmaco-economic report NScientific Advisory Committee size: 4 • Access plan NPolicy Advisory Committee size (if used): — • Advocacy plan N

LIST OF PARTNERS


World Health Organization Human Resources xxxCDC Human Resources

* GAVI Management committee



1 3 8

South African AIDS Vaccine Initiative Director: Dr. Tim TuckerLaunch date: 1999 Address: Francie Van Zijl DriveFocus: Vaccine coord (S.Africa) Medical Research CouncilTarget: HIV/AIDs Parow Valley, 7505Website: www.saavi.org.za

MISSION

A national body coordinating the research, development and testing of HIV/AIDS vaccines in South Africa with the aim of producing an affordable, effective andlocally relevant preventative HIV/AIDS vaccine.



Background of Management Team 10 40 60 —Background of Board 10 50 50 40Amount of capital contributed $45m 77 23 —Amount of in-kind contribution (est) $2m/year 90 10 —Ownership over pdts produced (est) All — — —R&D model/processes (est) — — — —

SCOPE OF ACTIVITIES



Research Y Y Y Y/NPre-clinical Y Y Y Y/NPhase I testing N Y Y YPhase II testing N N Y YPhase III testing N N Y YRegulatory approval Y Y Y/N Y/NManufacturing Y Y N Y/NSales/distribution N N Y/N NAdvocacy Y Y Y N

PORTFOLIO STRATEGY

Current 2004 portfolio (# of pdts) 8 Forecast end 2005 portfolio (# of pdts): 8• Pre-clinical: 6 • Pre-clinical: 5• Phase I: 1+(2) • Phase I: 2+(?)• Phase II: — • Phase II: (1)• Phase III: — • Phase III: —• In-market: — • In-market: —Number of clinical trials: — Number of clinical trials: 2Location of clinical trials: S. Africa, USA Location of clinical trials: S. Africa, USA


Number of professional employees: 200 Use of:Capital raised to date: $45m • Scientific blueprint YNumber of donors: ±7 • Business plan (Y)Board of Directors size: 10 • Pharmaco-economic report YScientific Advisory Committee size (if used): 13 • Access plan YPolicy Advisory Committee size (if used): 5 • Advocacy road map (Y)

LIST OF PARTNERS/STAKEHOLDERS

Contribution type* In-kind contribution financial value

Eskom SAR 67.5mDept. of Health, Dept. of Science and Tech. SAR105mSA MRC — —NIH SAR52.2m Yes, ?EU SAR9.9mUCT, U.S., U, Natal } SAR}Chiron, Cobra, Therion, Biovac, etc. etc. } SAR}70m

* Over 5 years

1 3 9

ANNEX 9C

PPPs and product development: Innovative financingopportunities and the need for a ‘business case’ approach

Amie Batson (World Bank), Rajiv Shah (Bill & Melinda Gates Foundation), Chris Gingerich (Consultant,Bill & Melinda Gates Foundation) and J. Niels Rosenquist (Consultant, World Bank)

Financing opportunity – Investors and the capital marketsThe primary benefit of the tax-exempt debt andsecuritization concepts are that they both shift moneyforward in time. However, in both cases the organiza-tion is leveraging existing financial resources to obtainimmediate financing – neither solution brings ‘newmoney’ to the table.

In contrast, both project finance and put optionsdo attract ‘new money’. However, the project financeconcept hinges entirely on the presence of an off-takeagreement, and the put-options concept can be real-ized only if there exists an entity willing to guaranteefuture purchase of the product at a fixed price shouldthe option be exercised. In both of these instances,the ability to attract new money is based entirely onthe premise of guaranteed future market for the prod-uct in question.

Investors seek to minimize the risk embedded intheir future investment returns. Within the context ofproduct development (PD) financing, the best avail-able risk minimization strategy is to guarantee a futuremarket for the product in question. Thus, in order toattract investor financing it is necessary to have a pur-chase contract in place.

Health product purchasers seek to minimize riskwith regard to procurement. Within the context of PDfinancing, purchasers will prefer to enter into off-takeagreements and underwrite put options as opposed tofinancing risky product development activities directly.

Donors and partners are as focused on investmentreturns as are investors and purchasers, yet they mayhave the highest overall risk tolerance. Donors may bewilling to finance product development directly –especially if they are willing to make the necessary long-term financial commitment.

Executive summary

Given the sheer size of the looming financing chal-lenge, PPPs need to look beyond traditional public

and donor financing sources if they are to meet thesignificant challenges of bringing multiple orphan prod-ucts to market. This paper looks beyond traditionalsources of financing for PPPs and analyses several ‘fromwhere’ and ‘how to’ opportunities for bringing newmoney to the table.

The paper is divided into three main sections:

• Financing opportunity – Investors and the capi-tal markets

• Financing opportunity – Development assistancefor health

• The business case – A tool for attracting financ-ing

Much of the information presented in this paper is theresult of research currently being undertaken in sev-eral working groups of which the authors are key par-ticipants. Additional components of the discussion arebased on learnings from early-stage efforts to imple-ment some of the concepts discussed in the paper. Thefinal section of the paper – which focuses on the busi-ness case method for presenting a financing projectproposal to funders – is based in part on work cur-rently being undertaken by a major funding resourcethat will reinvent the way that they approach grant-making. Our belief is that to the extent that PPPs areable to develop a competency in presenting their fund-ing proposals within a business case framework, theywill be better positioned to obtain financing from allpotential donors, whether traditional donors or newfunding sources.

Key conclusions from each of the major sections arepresented below.

A N N E X 9 C . P P P S A N D P R O D U C T D E V E L O P M E N T


1 4 0

Gordon Brown’s IFF proposal – A securitization exampleWe also provide a brief discussion of the InternationalFinance Facility (IFF) proposal. Key potential benefitsof the IFF derive from its ‘front-loaded’ financing pro-file. Costly introduction periods for vaccines or drugsincluding introduction pricing, up-front infrastructureinvestment and potential contributions to time-limitedcampaigns around polio and measles all may benefitfrom the way in which securitization makes long-termdonor funding commitments available in the near term.Front-loaded financing may also enable acceleratedprice maturity in vaccine markets, furthering countrysustainability goals.

Financing opportunity – Development assistance for healthTraditional mechanisms often fail to value and sup-port global public goods such as product development.Nevertheless, systematically approaching major bilat-eral and multilateral sources of funding is critical toobtaining necessary resources.

New financing mechanisms, whether new mecha-nisms at the World Bank or within the context of theUS government’s Millennium Challenge Account(MCA), represent a significant opportunity for fund-ing.

Understanding country systems for priority settingand developing country champions for the develop-ment and early introduction of key products representan important step for seeking bilateral or multilateralresources.

Multilateral grant funds and procurement mecha-nisms – such as the Vaccine Fund and perhaps aGFATM with more of a centralized leadership role incommodity procurement – can help create real marketdemand and thereby help unlock significant projectfinancing for product development.

The business case – A tool for attracting financingGiven that investors and donors do not operate on lim-itless funds, both for-profit investors and not-for-profitfunders must employ business-savvy strategies to evalu-ate potential investments. Many investors/funders inboth sectors assume a portfolio perspective, distribut-ing their investments across multiple specific objectives,and diversifying risk/benefit relationships within thoseobjectives. The review processes they use to evaluateapplicants increasingly reflect this perspective and rely

heavily on the ‘business case’ model of presentation.Thus applicants seeking funding from for-profit or not-for-profit investors must become adept at presentingtheir proposals as business cases if they are to commu-nicate the value of their project and funding proposaleffectively.

As potential recipients of investment funds, PPPsmust develop new competencies in this business casepresentation style. Armed with these tools for makingbusiness- or financial-style requests for funding, PPPswill be better equipped to apply to diverse and multi-ple investors and should have increasing success inobtaining funding.

Introduction and backgroundThe past four decades have seen few real breakthroughsin the development and introduction of health prod-ucts in resource-poor settings. Despite tremendousadvances in biomedical science and technology, fewinnovations have been developed to reduce the tre-mendous burden of disease of communicable diseasein developing countries. However, the need to addressthis lack of innovation in global health has receivedsignificant new attention in the past several years. Arange of public-private partnerships now exists to ac-celerate product development. The Vaccine Fund wascreated to finance the introduction of new andunderused vaccines, while the United Nations createdthe Global Fund for AIDS, TB, and Malaria. Buildingon these efforts, Jim Wolfensohn, president of theWorld Bank, assembled in 2001 the ‘Out-of-the-Box’(OOTB) group1 to “create, improve upon, and vali-date new strategies and incentives to accelerate thedevelopment and use of priority health products fordeveloping countries…”.

The group concluded that a strategy of minimizingdevelopment costs and risks while guaranteeing futurerevenues is fundamental to accelerating the develop-ment of new health technologies targeting the world’spoorest countries. The following is a list of the OOTBgroup’s initial recommendations for further investiga-tion:2

1 The group consisted of senior leaders from industry and thepublic sector, with particular focus on representation by fi-nance professionals specializing in health care.

2 See Out of the Box Meeting Notes, July 2001. (http://www.gaviftf.org/forum/background_docs.html)

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• Investing in early R&D: The public sector shouldbecome more active in reviewing and managingR&D portfolios relevant to priority diseases.

• Investing in manufacturing plants: The public sec-tor can mitigate risk and influence competition viatargeted investments in productive capacity.

• Establish not-for-profit subsidiaries: PPPs shouldexplore opportunities to create not-for-profit divi-sions focused on specific vaccines.

• Long-term purchase guarantees: Given the fun-damental barriers of risk and market uncertainty,long-term purchase guarantees are likely to be a nec-essary part of any solution.

• Role of World Bank/International DevelopmentAssociation (IDA) in purchase guarantees: Al-though the World Bank is not involved in the pur-chase of vaccines, it does have tremendous resourcesavailable to developing countries and should con-tinue to explore innovative concepts to facilitate thepurchasing of vaccines by developing countries.

• ‘Venture capital’ approach: Money may be investedin companies developing priority vaccines in ex-change for equity or ‘access stakes’.1

• Innovative use of capital markets: The capital mar-kets and related financing mechanisms may betapped as new sources of funding for global publicgoods.

Many of the above recommendations are relevant toPPPs as they contemplate the coordination of vaccinePD activities, including expensive phase III clinical tri-als. Given the sheer size of the looming financing chal-lenge, PPPs need to look beyond traditional public anddonor financing sources if they are to meet the signifi-cant upcoming challenges of bringing multiple orphanproducts to market.

This paper looks beyond traditional sources financ-ing for PPPs and analyses several ‘from where’ and ‘howto’ opportunities for bringing new money to the ta-ble. The paper is divided into three main sections:

• Financing opportunity – Investors and the capi-tal markets

• Financing opportunity – Development assistancefor health

• The business case – A tool for attracting financ-ing

Much of the information presented in this paper is theresult of research currently being undertaken in sev-eral working groups of which the authors are key par-ticipants. Additional components of the discussion arebased on information from early-stage efforts to im-plement some of the concepts discussed in the paper.The final section of the paper, which focuses on thebusiness case method for presenting a financing projectproposal to funders, is based in part on work currentlybeing undertaken by a major funding resource whichwill reinvent the way that they approach grant-mak-ing.

Our belief is that if PPPs are able to develop a com-petency in presenting their funding proposals within abusiness case framework, they will be in a better posi-tion to obtain financing from all potential donors,whether traditional donors or new funding sources.

Financing opportunity 1 –Investors and the capital marketsGiven the size and prominence of capital markets in-stitutions such as the stock and bond markets, and rec-ognizing the fundamental role played by capital marketsinstitutions such as commercial and investment banks,it is apparent that the they are a critical component tonearly every sector of the economy. Thus, the ques-tion remains as to why the capital markets have notbeen of equal prominence within the context of devel-oping new global health products for the world’s poor-est countries? Put differently, what opportunities existto leverage this potentially significant source of moneyand financial know-how? This section will attempt toanswer these questions.

The OOTB Group set up the Capital MarketsMechanisms (CMM) working group to investigatewhether capital markets tools could be applied to vac-cine financing.2 The working group believes that in-novative financing techniques which have provenvaluable in other industries may likewise generate sig-nificant progress in the world of vaccine financing. The

1 An ‘access stake’ gives the investor certain rights to the tech-nology if the firm does not provide developing countries with‘reasonable price’ access to the vaccine.

2 Group membership included several financial experts special-izing in areas such as securitization and asset finance, projectfinance, derivatives, emerging markets and tax-exempt debt,in addition to representatives from the public sector, founda-tions and industry.



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following are some simplified examples of how otherindustries use capital markets to achieve their financialand strategic objectives:

• A non-profit community hospital sells tax-exemptbonds to raise capital for the building of a new pae-diatrics wing. The hospital chooses tax-exempt debt– debt in which investors do not have to pay tax oninterest earned – to obtain a better financing ratethan they could otherwise obtain in a commercialfinancing arrangement.

• A developing country oil and gas company uses aproject finance structure to raise capital for the con-struction of a new oil refinery. The company usesproject finance to obtain financing terms specific tothe oil refinery project – a project with a precise,identifiable, future income stream – that are betterthan the terms they would be able to obtain basedupon the credit rating of the entire company.

• A family farmer purchases put options to guaranteea future market and hedge against the risk of lowcommodity prices during the next harvest. The putoptions secure for the farmer guaranteed prices andquantities that he can then choose to exercise ornot. These options allow farmers to minimize therisks they may encounter from an uncertain market.

Overview of capital markets and capital marketsmechanismsBroadly speaking, capital markets can be thought of asthe aggregation of the concepts presented in Table 1.

Fundamentally, capital markets serve to matchinvestors’ monies with those in need of financing. Capi-tal markets mechanisms are specific financial ‘arrange-ments’ that serve to structure the channelling of moniesamong issuers, borrowers, investors and intermediar-ies.

Table 1. Elements of the capital markets

Sub-markets Institutions Roles Mechanisms/Other

• Bond and fixed-income markets • Investment and commercial banks • Issuers • Securitization• Equity markets • Insurance & and asset management • Borrowers • Insurance and annuities• Money markets companies • Investors• Foreign exchange markets • Stockbrokers & and securities houses • Intermediaries• Derivatives, swaps, forwards,

futures and options markets• Credit markets

Perhaps the most familiar examples of capital mar-kets are the buying and selling of stocks and bonds. Inthe case of stocks, companies initially issue stock toraise money to be used in the business. Investors pur-chasing the stock are entitled to an equity (ownership)share in the business and a claim on any profits. In thecase of bonds, organizations initially issue bonds toraise money, just as with stocks. However, unlike stocks,which give the investor an equity stake in the business,bonds are simply a loan from investors to the companywhere the bond represents the company’s indebted-ness to investors.

At its initial meeting, the CMM group selected aset of four capital markets concepts considered to havethe greatest promise in terms of their applicability tofinancing vaccines or other global health product de-velopment:

• Tax-exempt debt (tax-exempt bonds)• Securitization• Project finance• Put options.

Each of these concepts and the conclusions of theCMM group are reviewed in more detail below.

Tax-exempt debtKey concept – Tax-exempt bonds: A bond issued bya municipal, county or state government (at times onbehalf of non-profit corporations), whose interest pay-ments are not subject to federal income tax (and aresometimes not subject to state or local income tax).

Key concept – Tax-exempt status: The interest in-come that investors receive on their municipal bondinvestment is exempt from federal taxation and oftenfrom state and local taxes. As a result, investors arewilling to accept a lower interest rate than they would

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if their income was taxable (i.e. the non-profit corpo-ration is able to borrow money at a lower rate).

Sample application and use of funds: Consider a sce-nario in which US$50 million is needed to finance theconstruction of a health product production facility. APPP might work with several credit-worthy donors/investors to raise this money by issuing US$50 millionworth of 10-year tax-exempt bonds. Note that for abond to be considered for tax-exempt status, the pro-ceeds of the bond must be used for a capital project bya recognized non-profit organization.

Source of funds: In this scenario, if the PPP were toborrow money by issuing tax-exempt bonds, it wouldfirst have to be in a position to repay both the princi-pal and the interest to borrowers. Thus, the PPP wouldhave to either have on hand the amount of the moneyit wished to borrow,1 or have iron-clad donor commit-ments that could be used as collateral (see securitizationbelow).

Evaluation: Debt, in general, enables borrowers im-mediately to access capital that they might otherwiseonly be able to access over several years. Tax-exemptdebt enables borrowers to borrow this money at a ratesignificantly lower than standard taxable commercialrates. When contemplating investments in the orderof tens or hundreds of millions of dollars, tax-exemptdebt may be attractive to donors and other projectsponsors if it enables them to spread a given cash com-mitment over a longer period of time while potentiallymaking higher returns on their invested capital. How-ever, ultimately tax-exempt debt is not a tool for rais-ing new money, but rather a tool for bringing forwardin time money that is already committed to – or likelyto be earned by – the PPP.

SecurizationKey concept – Asset securitization: A process wherebyloans, receivables (i.e. expected future income) andother assets with future income streams are bundledtogether into interest-bearing securities.

Key concept – Asset-backed securities: A securitywhere the promised interest and principal payments

Gordon Brown’s IFF proposalA securitization exampleIn response to the September 2000 Millennium Declaration andthe March 2002 Monterrey Consensus, the International FinanceFacility (IFF) was proposed by Gordon Brown, the United King-dom’s chancellor of the exchequer, as an actionable funding strat-egy to meet the financing requirements implied by theMillennium Development Goals. The IFF proposal seeks to dou-ble current international aid flows by raising an additional US$50billion a year.

Donors would make a series of 15-year pledges to the IFF, witheach pledge being a binding commitment subject to a high-levelfinancing conditionality (or ‘a way out’). Leveraging thesepledges, the IFF would securitize the donor pledges and issuebonds in its own name and thus turn the long-term incomestream from donors into capital available for more immediatedisbursement.

Figure 1. IFF income and disbursement patterns1

1 Figure 1 is taken from International Finance Facility, HM Treasury andthe UK Department for International Development (DFID), January2003 (available at: http://www.dfid.gov.uk/Pubs/files/International%20Finance%20Facility2003.pdf)

The facility would be replenished every three years, at which timedonors would make new long-term funding pledges to the IFFas the basis for further borrowing. The IFF would be in existencefor about 15 years with repayment continuing for, roughly,another 15 years after which the facility would close.

The financing profile enabled by the IFF is particularly relevantto certain front-loaded programmatic strategies currently beingpursued by global health agencies such GAVI. Costly introduc-tion periods for vaccines or drugs including introduction pricing,up-front infrastructure investment, and potential contributionsto time-limited campaigns around polio and measles all maybenefit from the way in which securitization makes long-termdonor funding commitments available in the near term. Front-loaded financing may also enable accelerated price maturity invaccine markets, furthering country sustainability goals.

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02006 2008 2010 2012 2014 2016 2018 2020 2022 2024 2026 2028 2030 2032

1 Or, it would have to have the expectation of market returnsthat would cover development costs over time.



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are backed by cash flows from an asset or portfolio ofassets that generate the cash flows.

Sample application and use of funds: A group of 10donors pledge to make annual payments to a PPP overa period of 20 years in order to fund a US$100 mil-lion, phase III clinical trial. Bundling these commit-ments together and selling these payment streams assecurities in the capital markets would yield cash avail-able for immediate use to fund the clinical trial overthe next several years. Since the commitments origi-nate from a variety of funders, the market would valuethe security based on the credit-worthiness of the un-derlying donors.

Source of funds: In this scenario, the original sourceof funds is the underlying donor commitments to thePPP. The proceeds from the sale of securities comefrom investors, but as with the tax-exempt debt exam-ple, all this money must be ‘paid back’ from the origi-nal donor commitments.

Evaluation: The basic structure of the securitizationscheme has many similarities to the tax-exempt debtexample – specifically, the feature of shifting moneyforward in time by ‘borrowing’ from the capital mar-kets. The main differences, however, are that in thesecuritization the PPP is selling an asset as opposed toborrowing money, and since there is no tax-exempttreatment, the costs of securitization are much higherthan for tax-exempt debt. The advantage ofsecuritization is that the proceeds can be used for anypurpose and are thus not limited to non-profit targetedcapital projects.

Project financeKey concept – Project finance: Non-recourse financ-ing for a specific project in which the lender looks tothe revenues the project may generate for the repay-ment of its loan, and the assets of the project serve ascollateral for the loan (rather than the assets of theproject sponsor).

Key concept – Project company: A company set upby the project sponsor(s) to own the project and raisefinancing (also known as a ‘special purpose vehicle’).

Key concept – Project sponsor: The sponsor, or spon-sors, that organizes, controls and makes an equity

investment in the project company. The sponsor(s) isnot liable for the financial obligations of the project.

Key concept – Off-take agreement: An off-take agree-ment is a contract between the project company and abuyer in which the buyer agrees in advance to pur-chase the output of the project company’s productionfacility.

Sample application and use of funds: Consider a PPPthat is seeking to develop and introduce an affordablevaccine, drug or other health technology for develop-ing countries. If the PPP could convince a major pur-chaser (e.g. UNICEF, the Pan American HealthOrganization (PAHO) or the Vaccine Fund) to enterinto a credible off-take agreement with a PPP-spon-sored project company, this project company could thenraise debt and equity in capital markets based on thestrength of the off-take agreement. Typically, theproject company would be formed to build additionalproduction capacity for an existing (licensed) product;however, if the off-take agreement was a ‘take or pay’contract,1 it may be possible to use project finance tocoordinate funding for product development (phaseIII trials).

Evaluation: If purchasers and/or donors are willing(and able) to enter into an off-take agreement with aPPP-sponsored project company, the project financestructure has real potential for attracting significantamounts of new debt and/or equity financing. Thisstructure is particularly attractive to purchasers anddonors because they only spend money for the actualpurchase of product (assuming there is no take or payagreement). However, if purchasers and donors arereluctant to enter into take or pay arrangements, thistool may be relevant to projects where the risky scien-tific and technical stages of product development havealready passed – potentially limiting its immediate use-fulness product development activities.

1 In a ‘take or pay’ contract, the buying party agrees to eithertake the product under the contract terms or pay a fee as speci-fied in the contract. In the case of funding for product devel-opment, the buyer would thus need to be willing to makepayments even in the case that the vaccine does not progressthrough licensure and there is no resulting product to pur-chase.

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The International Finance Corporation: Projectfinance for vaccine production capacity?The International Finance Corporation (IFC), a member of theWorld Bank Group, is a promising source of project finance-basedfunding. For example, the Vaccine Fund and UNICEF have ex-pressed interest in obtaining vaccines that are of high quality(WHO pre-qualified) but at a lower cost (less than the price of-fered by the current multinational vaccine manufacturer) thanare currently available. If the VF and/or UNICEF are willing to en-ter into a suitable off-take agreement with an emerging marketvaccine supplier, it is likely that the IFC would make financingavailable to the manufacturer for investment in productive ca-pacity. It is interesting to note, however, that many firms wouldbe able to secure traditional investor financing on their own ifthey were able to secure a long-term purchase contract with theVF or UNICEF, and thus would not need to seek financing fromthe IFC. This underscores the importance of purchase agreementsin causing investor monies to flow into vaccines being developedfor the world’s poorest countries.

Put optionsKey concept – Put option: A contract that gives theholder the right to sell a certain asset to the writer ofthe option, at a specified price (‘strike price’) up to aspecified date (‘expiration date’).

Key concept – Call option: A contract that gives theholder the right to buy a certain asset from the writerof the option, at a specified price (strike price) up to aspecified date (expiration date).

Sample application and use of funds: PPPs couldcoordinate the sale of put options to companies thatare contemplating or pursuing a specific priority drugor vaccine, such as malaria, research and developmentactivities. Purchaser and donor partners could under-write the options. Companies interested in pursuing amalaria product development programme could pur-chase put options to ensure market demand. In the

Table 2. Elements of put and call options

Buyer of option (holder) Seller of option (writer)

Put option Right to sell underlying asset at a pre-specified price Obligation to purchase asset from option holderup to a specified date (if option is exercised by holder)

Call option Right to buy underlying asset at a pre-specified price, Obligation to sell asset to option holderup to a specified date (if option is exercised by holder)

event that one or more option holders do get a prod-uct licensed and produced, the option holders can ‘call’their option, in which case the option writer will pur-chase a specified amount of product at the price speci-fied in the option contract.

Evaluation: The main benefit in this scenario is theresulting acceleration of investment in R&D, licensureand manufacturing. Credible put options provide in-centives for development without requiring cash up-front, and resources are only spent by donors or vaccinepurchasers if a suitable product is developed. How-ever, this concept is untested and the interest level ofvaccine producers in uncertain. Also, this concept doesnot raise significant new resources for procurement ifoptions are exercised.

Opportunity assessments for PPPs and productdevelopmentFurther consideration of the four concepts presentedabove reveals fundamental similarities across the tax-exempt debt and the securitization concepts, and acrossthe project finance and put options concepts.

The primary benefit of the tax-exempt debt and thesecuritization concepts are that they both shift moneyforward in time. Tax-exempt bonds enable organiza-tions to borrow money and receive cash immediatelybased on their ability to repay the debt in the future.Securitization enables organizations to sell assets andreceive cash immediately, provided the organization hasone or more assets suitable for securitization such as abook of accounts receivables or another long-termstream of payments owed to the organization. How-ever, in both cases the organization is leveraging exist-ing financial resources to obtain immediate financing.Neither solution brings ‘new money’ to the table.

In contrast, both project finance and put optionsdo attract ‘new money’. Project finance provides a con-text within which both debt and equity investors havean incentive to provide financing for the project com-



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pany; debt investors via loans to the project companyand equity investors via direct ownership investment.In the case of put options, the private firms that pur-chase the options are motivated either to invest theirown money in the project or to seek external financingfrom outside investors. However, the project financeconcept hinges entirely on the presence of an off-takeagreement, and the put-options concept can be real-ized only if an entity exists that is willing to guaranteethe future purchase of vaccines should the option beexercised. In both of these instances, the ability to at-tract new money is based entirely on the premise ofguaranteed future market for the product in question.

When applying the four concepts to funding phaseIII trials for a developing country drug or vaccine, simi-larities can be seen between the tax-exempt debt andthe securitization concepts, and between the projectfinance and put options concepts.

Tax-exempt bonds and securitization may enable aPPP to transform financial resources available only overthe long term into money that could be used to fundproduct development activities in the short term. Theability to execute a financing strategy that relies onone of these concepts is not dependent on orchestrat-ing a guaranteed future market for the product in ques-tion. The only limitation is that in the case oftax-exempt bonds the proceeds must be used for non-profit capital projects, and thus may not be availableto fund personnel, supplies, etc., to other non-capitalexpenses.1

The project finance and put options concepts donot depend on the financial strength of the PPP, butrather on the strength of the off-take agreement(project finance) or the financial strength of the putoption writer. The challenge in these cases is to getinvestors and/or firms to invest money in a risky phaseIII clinical trial, even with a guaranteed market for asuccessful product. Traditionally, project finance inves-tors – especially debt investors – would not accept thehigh levels of risk inherent in clinical trials and thuswould not make the necessary investments needed tofund an expensive phase III trial. However, project fi-nance investors would very likely be interested in pro-viding funding for productive capacity investments forlicensed products. The same basic logic applies to theholders of put options. If a firm holds enough optionsto guarantee a market for their product if it success-

fully emerges from clinical trials, it might still have dif-ficulty attracting external investors due to the comple-tion risks inherent to phase III trials, and may evenface stiff opposition to funding the project internally ifthe market size is not large enough and/or the trial orproduct is perceived as especially risky.

From the perspective of attracting the initial finan-cial commitment to initiate any of the four conceptsmentioned above, one might expect that it would bemore challenging to attract the initial financing for thetax-exempt debt and securitization scenarios. This isbecause for these instances, the risk of a negative out-come from the phase III trial falls to the initial donorsand partners. Presumably in this scenario, a PPP couldattract long-term financial commitments from donorsand partners based on the prospect of using one ofthese financing tools to turn the long-term commit-ment into money available immediately to finance PDactivities. Thus, the donor or partner is directly financ-ing the PD activities, only via a commitment that isspread out over a longer term than what is actuallyneeded to fund the trial. The essential argument madeto donors and partners in this case is to convince themto fund PD activities for which there is an ‘all or noth-ing’ outcome.

Conversely, in the case of project finance or putoptions, the vaccine purchaser who enters into the off-take agreement or writes the put option is shieldedfrom the risk of the clinical trial.2 In this case, the pur-chaser is simply stating that they will purchase the prod-uct conditional upon the successful completion of thetrial and the subsequent production of a licensed prod-uct. For purchasers such as the Vaccine Fund that existto buy vaccines – and are interested in seeing newvaccines come to market – they might be expected tobe willing participants in such a scheme.

Investors and capital markets – ConclusionsThe factor underlying much of the above analysis isrisk, and which parties are willing and able to bear whichtypes of risk.

1 Note, however, that PPPs could still pursue the use of debtthrough standard taxable bonds, which would not have re-strictions on the use of proceeds.

2 This assumes no take-or-pay agreement. In the case of a take-or-pay agreement, the risk of the clinical trial falls to the vac-cine purchaser (the buyer in the off-take agreement).

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With this in mind, perhaps the most likely outcometo emerge would be a multi-party project finance ar-rangement with the following characteristics:

• A vaccine or drug manufacturer sponsors a projectcompany to pursue phase III clinical trials for theproduct in question.

• One or more purchasers enter into an off-take agree-ment with the project company in which they agreeto buy ‘x’ million doses per year over a ‘y’-yearperiod at a price of ‘p’ dollars per dose.

• One or more donors would agree to ‘insure’ theoff-take agreement and transform it into a take-or-pay contract in which the donors would be re-sponsible for making the payments should the prod-uct not emerge successfully from trials.

• One or more investors would provide a combina-tion of debt and or equity financing based on thestrength of the take-or-pay off-take agreement.

In the above scenario, the only party bearing any sig-nificant risk is the donors. However, this may be a plau-sible scenario for donors if you consider that theiralternative would be to fund the PD activities directly.Under the direct funding scenario, donors have a 100%probability of a cash outlay, and some unknown prob-ability of a ‘successful’ outcome. In the take-or-payscenario, donors have much reduced probability of in-curring a cash outlay and the same unknown probabil-ity of a ‘successful’ outcome. Rationally, the take-or-payscenario is preferable for donors; however, it may bedifficult for them to get over the mindset of commit-ting to pay only in the case of an ‘unsuccessful’ out-come.

Based on the above discussion, we might draw thefollowing conclusions with regard to how best to in-volve specific funding sources when seeking financingfrom the capital markets:

• Investors. Investors seek to minimize the risk em-bedded in their future investment returns. Withinthe context of PD financing, the best available riskminimization strategy is to guarantee a future mar-ket for the product in question. Thus, in order toattract investor financing, it is necessary to have apurchase contract in place, which may take the formof a put option or an off-take agreement within aproject finance context.

• Health product purchasers. Purchasers seek tominimize risk with regard to procurement. Withinthe context of PD financing, purchasers will preferto enter into off-take agreements and underwriteput options as opposed to financing risky PD activi-ties directly.

• Donors/partners. Although donors and partnersare as focused on investment returns as are inves-tors and purchasers, donors may be the group withthe highest level of overall risk tolerance. Donorsmay be willing to finance product development di-rectly – especially if they are willing to make thenecessary long-term financial commitment and theyfind the cash-flow advantages of debt andsecuritization financing attractive. Donors may alsobe willing to assume all or some of the associatedresponsibilities with the roles described above forinvestors and purchasers.

Financing opportunity 2 –Development assistance for healthRecent estimates of additional donor resources requiredfor development assistance for health (DAH) rangefrom US$15 billion to US $27 billion per year. Whilefar short of that goal, official DAH has risen from anaverage of US$6.7 billion in the period from 1997 to1999 to an average of US$8.1 billion between 2000and 2002. This upward trend has accelerated in recentyears with donors making significant new commitmentsto the Global Fund for AIDS, TB and Malaria, theVaccine Fund and other new structures to promotedevelopment, including two major US initiatives – theUS president’s new initiative for HIV/AIDS and theMillennium Challenge Account.

These funds flow through a variety of financialmechanisms including bilateral agencies (such asUSAID, DFID and JICA, the Japanese InternationalCooperation Agency), multilateral development banks(World Bank and regional development banks), othermultilateral funds and agencies including the UN sys-tem (especially WHO, UNICEF and the UN Popula-tion Fund (UNFPA)) and private foundations. Thefollowing section provides a brief overview of the DAHlandscape.



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Overview of development aid for healthBilateral donors: In absolute dollar terms, the UnitedStates government is the largest single donor – account-ing for between 20 and 40per cent of all DAH, fol-lowed by Japan, the United Kingdom, Germany, Franceand Scandinavian countries. (Note that when comparedto the overall size of the US economy or the federalbudget, US commitments to development lag behindmost donors. The US only provides 0.1 per cent of itsgross domestic product (GDP) as official aid, comparedto an average of over 0.3 per cent for all donors, whilethe UN’s stated goal is 0.7 per cent of GDP.) US bilat-eral funding, with the exception of commitments tothe GFATM and VF, has remained relatively verticalthrough a range of existing and new disbursementstructures – including USAID, the CDC, the NIH,and the president’s new initiative on HIV/AIDS. As aresult, the appropriations and administrative structuresin the US are able to move resources with a greatdegree of donor discretion. Most European bilateraldonors prioritize relatively horizontal funding mecha-nisms including direct budget support to countries andsupport for multi-donor long-term sector plans (knownas sector-wide approaches, or SWAps). These Euro-pean donors therefore prioritize recipient country-based resource allocation decisions and are less likelyto make those decisions within central administrativeprocesses.

UN system, including multilateral developmentbanks: Within the UN system, DAH rose from an av-erage of US$1.6 billion during 1997–99 to US$2 bil-lion in 2002. Commitments from the developmentbanks remained stationary at around US$1.4 billion.However, changes in accounting by the World Bankto include financing for health contained in non-healthprojects (e.g. urban, water and sanitation, budget sup-port, etc.) suggest that its new commitments for healthactually rose from around US$1 billion in 2001 toUS$1.3 billion in 2002 and to US$1.7 billion in 2003.The World Bank provides country-specific supportwithin the context of two major lending vehicles – theInternational Development Association (IDA) and theInternational Bank for Reconstruction and Develop-ment (IBRD). IDA loans, known as credits, are forlow-income countries, have a 40-year repayment win-dow and a zero-interest rate, and allow for no repay-ment for the first ten years. As a result, two-thirds of

an IDA loan can be thought of as a grant and IDA isoften the focus for providing highly subsidized lend-ing to poor countries.

New multilateral funds: Two other important in-creases in DAH came from the GFATM, which com-mitted nearly US$1 billion to disease-control projectsin 2002, and from the Bill & Melinda Gates Founda-tion, which saw its financing for health increase fromaround US$450 million annually in 1997–99 to aboutUS$600 million in 2002.

Other: Although not formally considered official de-velopment assistance (ODA), a number of internationalfinancial institutions exists that could provide projectlending or credit to efforts to develop products in de-veloping countries. The most notable is the Interna-tional Finance Corporation which provides projectlending to the private sector in developing countriesand often serves as a lead lender. bringing in other pri-vate sector lenders with it. Other structures includethe Overseas Private Investment Corporation (OPIC)and national export-import banks.

Trends and new opportunities to seek support withinfinancing mechanismsSupport for PD activities – especially costly phase IIIclinical trials – clearly is not a priority for traditionaldevelopment assistance financing mechanisms. Manymechanisms are driven by resource allocation decision-making and requests at the country level, and few coun-tries (if any) will have the incentive to defray assistancetoday in order to invest in PD efforts that may or maynot provide greater options for reducing health ineq-uity in the future. This incentive problem has beendescribed as an inability of the development financearchitecture to provide for global or regional publicgoods such as breakthrough new technologies (i.e.,AIDS, malaria or TB vaccines). Nevertheless, recenttrends in development financing may provide a newset of options to finance product development.

Multilateral development banks, including the World BankMost World Bank lending – including IDA and IBRDlending – either supports country-specific projects orlarger programmes (including structural adjustmentand sector-wide programmes). As a result, most allo-cation decisions within the Bank’s financial flows are

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at the country level and with a combination of WorldBank managers, ministries of finance and project lead-ers. Thus, the Bank often plays a fairly limited role inproviding resources for global public goods that seemto have less direct value to countries than specific pov-erty alleviation projects. Furthermore, IDA and IBRDcan only issue loans and credits to sovereign entities –so directly supporting commercial activities of NGOactivities can be difficult.

To obtain World Bank resources for product devel-opment, PPPs must convince countries to invest theirBank resources in PD – including such activities as phaseIII trials. While unreasonable for many R&D activi-ties, this approach may be possible for important bur-den-of-disease studies and trials for efficacy and/oreffectiveness (if these phase III and IV trials are in thecountry in question).

The alternative approach would be to convincecountries to include line items for procurement for theproduct in question in their sector-wide plans andhealth programmes. This procurement-based approachhas some positive attributes. Including such line itemsin future sector plans indicates a willingness to intro-duce and use products that help convince manufactur-ers and international health agencies that demand – interms of need, desire and resource availability – existsfor the product once developed. Furthermore, WorldBank and health procurement systems can then aggre-gate this future demand across countries and help sup-port the establishment of markets for firms (including,perhaps, purchase guarantees) – potentially unlockingsources of private sector capital from the capital mar-kets to support costly product development efforts.Finally, including these line items in future sector planswould accelerate the Bank’s efforts to explore and cre-ate purchase guarantees. (The Bank is at present ex-ploring creative strategies such as establishing ‘regional’lines of credit, using IDA grants and facilitating IDA‘buy-downs’ to facilitate country financing of priorityvaccines. The Bank could also explore ways of using itspolicy dialogue with ministries of finance and health toraise the priority of immunization and vaccine financing.)

Few models exist for building this type of specific,future procurement support into development lend-ing mechanisms. However, models such as GAVI’sAccelerated Development and Introduction Plans(ADIPs) may encourage this type of support by pursu-

ing efforts to build and solidify product demand at thenational level in countries likely to be early technologyadopters. But it is important to note that existing Bankinstruments are not well adapted for focused, multi-country efforts such as vaccine purchase guarantees.Even if countries signalled broad commitment, simul-taneously preparing and implementing projects in nu-merous countries might be dif ficult and slow.Furthermore, the countries must implement funds fol-lowing the Bank’s procurement requirements (includ-ing international competitive bidding), which couldbe a stumbling block.

One important example that could serve as a modelfor future global health efforts is the polio eradicationinitiative (PEI). Countries can submit polio eradica-tion project applications to the World Bank for fund-ing, and the Bank provides IDA credits to execute theseprojects. Once the project is complete, as documentedby WHO, the country’s remaining debt to the WorldBank is paid for by donors through a Polio Eradica-tion Trust Fund established at the Bank. Rotary Inter-national and the Bill & Melinda Gates Foundation haveeach made up to US$25 million available through thetrust fund. The net result is that the programme shouldcost the country few resources if executed appropri-ately. The programme appears to be successful – witha handful of countries (including Nigeria, Pakistan andAfghanistan) taking IDA credits to help eradicate po-lio. A critical component to the programme’s successis its ‘turnkey’ nature. Since the PEI can help developa robust project plan, and since the trust fund estab-lishes an expedited process for moving the projectthrough Bank processes, country decision-makers andcountry-specific World Bank task teams find the effortappealing. Such an effort could be a model for the in-troduction of new products or the late stage develop-ment and testing of near-ready products in globalhealth.

Multilateral funds and agenciesIn recent years, new multilateral funds have helpedmobilize interest, donor commitments and global re-sources to address disease or product-specific issues inglobal health. Two new examples, GFATM and theVaccine Fund, are noteworthy as commitments to pro-cure products may help developers access privatesources of capital. The VF has raised over US$1.3 bil-



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lion in commitments to support the introduction ofnew and underused vaccines in nearly 75 countries.Since the Fund allows donors to pool their resourcescentrally for the purpose of product procurement anddistribution, it is able to articulate demand to manu-facturers, sign longer-term contracts and reduce mar-ket risk for industry. As a result, VF commitments maybe able to drive private sector resources to PD efforts.For example, if the VF could indicate a potential will-ingness to procure a certain product, given some basiccriteria (i.e. WHO regulatory approval), then productdevelopers could access both public and private lend-ing from a range of potential debt or equity investors,including the International Finance Corporation.

So far, other multilateral funds (including GFATM)have been slow to take advantage of global efficienciesin product planning, demand aggregation and strate-gic procurement, and therefore many new sources ofpotentially critical PD finance remain difficult to ac-cess. However, some signals indicate that these trendsare improving. WHO has evaluated the performanceof the TB drug facility and noted that centralized fa-cilities which provide support for financing, procure-ment and demand management have a critical role toplay in global public health. They are exploring similarefforts in other areas, including those relevant toGFATM operations.

Bilateral donorsThe overwhelming trend in bilateral financing is to-wards direct country support and participation inSWAps and country allocation decisions. As a result,the discussion related to the World Bank above isincreasingly true for bilateral donors as well. The ex-ceptions, as noted above, remain the US and Japanwhere direct support from key technical agencies maycontinue to be a significant source of funding support.

One major new effort is worthy of discussion: theUS’s Millennium Challenge Account. The MCA, whichwill probably provide several billion dollars for devel-opment assistance, remains relatively undefined. Nev-ertheless, some basic principles of this new initiativeare known. It will react to country proposals for fund-ing which could include proposals from both the pub-lic sector and the private, including NGOs or perhapscommercial sector enterprises. The MCA has publisheda set of country criteria. Initial funding will therefore

probably focus on a handful of qualifying countries withprogramme and planning support provided to abroader range of countries which are currently not eli-gible for assistance. Country-based proposals for large-scale trials or product introduction efforts would beappropriate, and the MCA is likely to accept applica-tions directly from NGOs, PPPs and commercialenterprises.

Development aid for health – ConclusionsA review of financing opportunities within the contextof development assistance for health leads to the fol-lowing conclusions:

• Traditional mechanisms often fail to value and sup-port global public goods such as product develop-ment. Nevertheless, systematically approachingmajor bilateral and multilateral sources of fundingis critical to obtaining necessary resources.

• New financing mechanisms, whether new mecha-nisms at the World Bank or within the context ofthe MCA, represent a significant opportunity forfunding.

• Understanding country systems for priority settingand developing country champions for the devel-opment and early introduction of key products rep-resents an important step for seeking bilateral ormultilateral resources. Efforts such as the ADIPscould be a model here.

• Multilateral grant funds and procurement mecha-nisms, such as the Vaccine Fund and perhaps aGFATM with a more centralized leadership role incommodity procurement, could help create real mar-ket demand and thereby help unlock significantproject financing for product development.Leveraging these mechanisms means using the like-lihood of markets (future procurement) to unlockdollars from capital markets today.

An ability to work on these four areas of resource mo-bilization is central to the task of raising necessary fundsfor product development and preparing the groundsfor successful and early introduction of products.

The business case – A tool for attracting financingThe need for the business case approachGiven that investors and donors do not operate on lim-itless funds, both for-profit investors and not-for-profit

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funders must employ business-savvy strategies to evalu-ate potential investments. Many investors/funders inboth sectors assume a portfolio perspective, distribut-ing their investments across multiple specific objectives,and diversifying risk/benefit relationships within thoseobjectives. The review processes they use to evaluateapplicants increasingly reflect this perspective and relyheavily on the business case model of presentation.Thus applicants seeking funding from for-profit or not-for-profit investors must become adept at presentingtheir proposals as business cases if they are to commu-nicate the value of their project and funding proposaleffectively.

A business case seeks to outline a specific product’sability to generate a return on investment (ROI) andto present an organized package of context, methodsand analysis in support of the ROI assertions. To for-profit investors, ROI is in general a financial conceptexclusively and is characterized by the total profit re-turned from the project in relation to the total invest-ment made in the project. For not-for-profit funders,ROI takes on a broader meaning, but remains a con-cept central to the business case. For these funders,ROI is characterized in terms of total programmaticbenefit in relation to the total amount invested. As re-gards global health, the total programmatic benefitmight be measured in terms of health outcomes suchas deaths averted or overall morbidity reduction, or interms of other more intermediate programmatic ob-jectives such progress towards product licensure orsuccessful construction of a vaccine or drug manufac-turing facility. No matter how a particular fundingsource defines ROI, once provided with this ‘package’of information, both for-profit and not-for-profit in-vestors/funders can readily evaluate a funding proposalbased on its overall opportunity, financial soundness,proposed ROI and compatibility with the investor’sparticular strategy.

As potential recipients of investment funds, PPPsmust develop new competencies in this business casepresentation style. Armed with these tools for makingbusiness- or financial-style requests for funding, PPPswill be better equipped to apply to diverse and multi-ple investors and should have increasing success inobtaining funding.

This section seeks to provide a general introductionto the business case approach. First, the basic compo-

nents of a business case are introduced and detailed,focusing on key items required by investors. Second,guidelines for adapting the business case format to thenot-for-profit sector are delineated. Finally, an actualoutline of a business case style proposal is presented inthe appendix.

Components of a business caseA business case framework contains a set of criteria thatenables the potential investor to make an informedinvestment decision. The investor wants to know twothings: what is the potential return on investment; andcan the project succeed in providing that return? Inorder to assess these questions efficiently, an effectivebusiness case-style funding proposal will contain thefollowing components:

• a market analysis• a project description• a financial analysis• a return on investment analysis.

Market analysisThe market analysis presents current market charac-teristics and analyses the new product’s ability to per-form, given those characteristics. It emphasizes themarket need for the product and the product’s pro-posed strengths.

Market characteristics: A description of the marketshould include its size, growth potential, competitionand market segmentation:

• The size of a market, estimated by multiplying theoverall quantity demand for the product by the prod-uct’s proposed price.

• The growth potential of the market will be influ-enced by variety of factors (population growth, in-come growth, macro trends, etc.). If possible, marketgrowth should be quantified.

• Discussion of the competition should include char-acteristics of competing products and product sub-stitutes, and how those products compete on price,quality and other features with the main product inquestion. It should also review the companies thatproduce these competitive products.

• Market segmentation refers to the phenomenonwhereby markets are divided into groups of buyerswho share a similar response to a given set of mar-



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keting efforts. A market analysis should describethose market segments that the new product seeksto target as potential buyers.

Product characteristics: An analysis of the product’sinteraction with the market should include a generalproduct description, product characteristics that willenable it to compete and estimated market share. Fea-tures such as quality, differentiation and price influ-ence the product’s competitiveness and also determinethe market share, or the product’s share of the totalsales within its category.

Project descriptionThe project description should outline the process tobring the product to market. The goal of this sectionis to provide evidence to investors that the proposedplan has been thoughtfully developed, and is feasibleand affordable. This evidence is provided through thefollowing:

• A project outline which focuses on the who, what,where and how of each step in the process. Thesesteps include, for example, research, development,manufacture, distribution and marketing.

• A discussion of the key risks and constraints thatcould threaten the project.

• A timeline with milestones, which consistently par-allels the project outline.

• An introduction of the project team detailing theirbackground and qualifications.

• A discussion of how to monitor the project and howto assess whether milestones have been attained.

Financial analysisThe financial analysis is designed to highlight the fi-nancial aspects of the project in question. Total costsand general allocation of funds should be covered inthe body of the business case, while itemization of in-dividual costs may be included in supplementary ma-terials. Some key components of the proposal include:

• A summarized budget, including total costs of theproject by major category and fiscal year.

• A proposed timetable for fund-raising and projectinitiation.

• Pro-forma financial statements or model, if appro-priate.

• The proposed financing of the project: Currencyand amounts itemized by source.

• Assessment of risks in financing that could impactproject cost and ultimately profits.

• A description of current financing already obtained(if any) and its source(s).

• The share the investor will receive of the generatedincome.

• A thorough discussion of assumptions used in de-veloping the analysis.

Return on investmentThe ROI component synthesizes the information inthe market analysis, project plan and financial proposal.The ROI part of the overall business case need notnecessarily be a ‘stand-alone’ section, but may be in-cluded in another section as appropriate (e.g. the fi-nancial analysis).

The ROI section seeks to present a measurable ex-pected outcome, or return, which justifies investmenton the part of the investor. For example, the ROI analy-sis might demonstrate – based on information pre-sented in the market, product and financial analyses –that an investment of US$25 million would be expectedto return US$40 million over the following five yearsbased on expected future sales.

Investors often perform their own sensitivity analy-ses that may lead to different assessments of the finalROI. It is important that the analyses presented withina business case be as transparent as possible in disclos-ing risks and constraints of the project and in layingout key assumptions. In summary, the ROI is only asstrong as the assumptions and analysis that lead to it.

Adapting a business case for not-for-profit fundersThe usefulness of the business case approach is not lim-ited to the for-profit sector. The not-for-profit sectoralso seeks a return on its investment and must choosefrom among a variety of investment opportunities toachieve its goals. While some funders, such as the WorldBank and IFC, have for years required funding appli-cations to follow such a model, other funders such asGAVI are only now developing fund allocation frame-works that leverage the business case framework.

While a business case can be a highly effectivemethod of applying for funds from the for-profitsector, it is necessary to tailor one’s approach to a not-

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for-profit framework. Such investors, by definition,define their mission and measure success using out-comes other than a purely financial ROI. Therefore, afunding proposal targeting a not-for-profit investormust begin by defining ROI in a manner consistentwith the funder’s programmatic goals and investmentstrategy. Below are some of the differences, by busi-ness case component.

Market analysisThis area, which can also be referred to as a ‘problem’or ‘opportunity’ analysis, should focus on understand-ing a funder’s overall goals and the product’s ability toaddress these goals. In place of market size, other meas-ures must be used to define the scope of the problemor opportunity. Instead of assessing the market in termsof competitors, funders are interested in assessing theavailable alternatives for addressing the problem. Theyalso will evaluate product’s potential for adding valueto efforts in controlling the problem. Some examplesmight include:

• Estimates of deaths averted or other key outcomesmeasures.

• Current and projected burden of disease by regionand demographic group.

• Current treatments available, such as mosquito netsfor malaria.

• Explanation of why current treatments lack effec-tiveness.

• Expected impact of product on the burden of dis-ease over time.

• Future products on the horizon and how they mightmitigate impact of vaccine being developed.

Project descriptionThere is limited need for modification of this section,since both types of funders are equally concerned withthe thoroughness and feasibility of the project plan.However, one area of note for applicants for not-for-profit funding is whether the project proposal is con-sistent with the funder’s organizational and governance

context. For example, an investor may require thatcertain affiliated organizations be included in a scien-tific review panel. In such a case, the project plan and/or key personnel may need to be modified to accountfor such specific requirements.

Financial proposalAdaptation of this component to the not-for-profitsector is, again, a fairly simple process. Non-profit in-vestors want to make sure a financial plan is detailedand prudent within the context of the investor’s port-folio strategy.

Return on investmentUnlike for-profit investors, who conceptualize ROI infinancial terms, not-for-profit funders assess returnmainly on the basis of programmatic objectives andhealth outcomes. In this case, it is necessary to adaptthe concept of ROI accordingly, and perhaps incorpo-rate cost-effectiveness measures to facilitate compari-son with competing investment opportunities (see Table3).

Business case – ConclusionsSuccessful for-profit private investors have become soon the basis of a sound portfolio strategy that includesa strong framework for assessing potential investments.Not-for-profit investors are increasingly adopting thebusiness case framework to insure that they invest theirlimited resources in the most effective manner possi-ble.

By using a business case model as a foundation fortheir funding proposals, PPPs can seek funding from awide variety of sources, building a powerful case basedon measurable outcomes for the investor. While per-forming the analyses required for such an approachcan be at times challenging due to the difficult-to-predict nature of the market and public health out-comes, it allows applicants to present their strongestcase to investors.



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APPENDIX

International Finance Corporation fundingproposal templateIFC proposal template1

1. Brief description of project.

2. Sponsorship, management and technical assist-ance• History and business of sponsors, including fi-

nancial information.• Proposed management arrangements, and names

and curricula vitae of managers.• Description of technical arrangements and other

external assistance (management, production,marketing, finance, etc.).

Table 3. Tailoring a business case for for-profit and non-profit investors

For-profit sector Non-profit sector

Key • What is the financial ROI? • What is the expected benefit (cost-effectiveness) of the project?questions • Can the project in question deliver the expected ROI? • Can the project in question deliver the expected ROI?

• Does the project fit within the investor’s investment strategy?

Market • Size of market (financial) • Size and distribution of ‘“problem’” (burden of disease, etc)analysis • Expected market growth • Expected size of problem over time

• Competitors, both current present and future, in the market • Current Present and future alternatives to addressing problem• Expected market share of product • Expected impact of product on problem over time

Project • Who will run the project? All of the for-profit sector steps, plus:description • What is the action plan? • How does the structure of the action plan fit within the

• What are the risks involved in the project? organizational context and investment strategy of the• What is the timeline for the project, (includewith key funder?

milestones)?• Who will assess the project’s attainment of milestones,

and how?

Financial • Detailed budget by area and over time • Detailed budget by area and over timeproposal • Total funding requirement and expected source(s) of • Total funding requirement and expected source(s) of

financing financing• Description of how expected income will be distributed

among investors

Return on • What is the ROI to investors (based on expected product • What is the expected benefit for the investment (cost-investment market share, project costs, and distribution of generated effectiveness), based on the expected impact of the product

income)? and the overall cost of the project?• What other, non-quantifiable benefits does the project/product

provide which fulfillfulfil the investment goals of the funder?

3. Market and sales• Basic market orientation: local, national, regional

or export.• Projected production volumes, unit prices, sales

objectives and market share of proposed venture.• Potential users of products and distribution chan-

nels to be used. Present sources of supply forproducts.

• Future competition and possibility that marketmay be satisfied by substitute products.

• Tariff protection or import restrictions affectingproducts.

• Critical factors that determine market potential.

4. Technical feasibility, manpower, raw material re-sources and environment• Brief description of manufacturing process.• Comments on special technical complexities and

need for know-how and special skills.• Possible suppliers of equipment.1 http://www2.ifc.org/proserv/apply/proposal/proposal.html

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• Availability of manpower and infrastructure(transport and communications, power, water,etc.).

• Breakdown of projected operating costs bymajor categories of expenditures.

• Source, cost and quality of raw material supplyand relations with support industries.

• Import restrictions on required raw materials.• Proposed plant location in relation to suppliers,

markets, infrastructure and manpower.• Proposed plant size in comparison with other

known plants.• Potential environmental issues and how these

issues are addressed.

5. Investment requirements, project financing, andreturns• Estimate of total project cost, broken down into

land, construction, installed equipment andworking capital, indicating foreign exchange com-ponent.

• Proposed financial structure of venture, indicat-ing expected sources and terms of equity and debtfinancing.

• Type of IFC financing (loan, equity, quasi-equity, a combination of financial products, etc.)and amount.

• Projected financial statement, information onprofitability and return on investment.

• Critical factors determining profitability.

6. Government support and regulations• Project in context of government economic

development and investment programme.• Specific government incentives and support avail-

able to project.• Expected contribution of project to economic

development.• Outline of government regulations on exchange

controls and conditions of capital entry and re-patriation.

7. Timetable envisaged for project preparation andcompletion.


ANNEX 9D

Portfolio management in thepharmaceutical industryEsther Schmid (Research Strategist, Pfizer UK)

potential drugs be discovered?); and development fea-sibility (can the hypothesis be tested at reasonablecosts?).

Portfolio management in actionRisk reduction through exclusion of high-risk projects(project-specific risk)A typical project consists of a ‘drug target’ (the receptor,enzyme or organism that causes disease) and associ-ated compounds (the chemicals that interact with thedrug target). Both drug targets and compounds canfail for a variety of reasons. Even a century of R&Dexperience has given the industry only partial insightsinto why projects fail, and not many of these insightshave prospective value. This means that winners can-not be selected, but (some) obvious losers can be dis-carded (based on technical infeasibility). So even beforeany physical work has started, experienced drug dis-coverers can often decide whether a project has hardlyany chance of delivering a medicine. This first-leveldecision removes the losers before costs are incurred(see Table 1). Such stratification of high-, medium- andlow-risk projects can be useful for investment decisions,as well as to achieve a risk-balanced portfolio.

Table 1 only illustrates a generic methodology, whichmost pharmaceutical companies would follow, albeitwith different degrees of granularity, weighting of fac-tors and types of factors considered.

The projects that remain are included into the port-folio if they meet cut-off criteria for commercial anddevelopment feasibility. But they still carry both knownand unknown risks regarding technical feasibility andmany will be ‘killed’ at different stages of the R&Dprocess. The earlier such ‘kill’ decisions are made, thelower the costs incurred. Most pharmaceutical com-panies have made significant investments in order to

Executive summary

Research and development (R&D) into new medi-cines is inherently risky. On average, only 1 in 10

new project ideas will deliver a development candidate,and only about 1 in 20 development candidates willever reach the market as a medicine. However, not allprojects carry the same level of risk, and some of theserisks can be reduced with relatively small investments.The aim of portfolio management is not to eliminaterisk altogether (which would be impossible anyway),but to maximize the chance of success whilst limitingcosts and time.

Purpose of portfolio managementPortfolio management is a routine part of running apharmaceutical R&D function. Senior R&D manage-ment use it on an ongoing basis to manage risk, costand output. Key portfolio performance indicators (e.g.,survival rates, numbers in stage, time to next milestone,etc.) are used both prospectively and retrospectivelycontinually to optimize portfolio content and perform-ance across all nine major stages of R&D. The objec-tives of portfolio management are threefold:

• Risk balance: For this, high-risk and low-riskprojects are combined at required ratios

• Maximizing the chance for a new medicine: De-pending on the overall risk profile, a smaller or largernumber of projects must be included in the port-folio

• Managing time to market: Projects at differentstages of maturity should be part of the portfolio sothat failing projects can be replaced quickly.

Portfolio entry is managed by evaluating projects alongkey axes: commercial opportunity (based on patientnumbers and medical need); technical feasibility (can


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acquire the necessary data for kill decisions as early aspossible. Such investments include computer simula-tion models of compound-target interactions; acquisi-tion and maintenance of large databases to linkcompound structures with toxicity problems: high-throughput screening technologies: and test-tubemodels, which mimic disease processes. The key aimof these large, up-front investments is to allow indi-vidual projects to accumulate more relevant informa-tion earlier in the R&D process so that informeddecisions can be made at lowest possible costs. Thiswill not always result in project termination – oftenthe information can be used to change the chemicalstructure of the compounds made in order to advancealong a different path.

Management of systematic risk through portfolio approachDespite the best efforts of the pharmaceutical indus-try, it has recognized over the years that an undesir-ably large part of project risk is systematic, i.e., inherentin the R&D process. Therefore, all pharmaceuticalcompanies, even smaller ones, use portfolios to man-age systematic risk. This approach does not reduce sys-tematic risk – rather it accepts that R&D is partly basedon luck, and that many attempts are needed to achievean overall goal. This statistical approach is used to buildan optimized portfolio (in terms of the number ofprojects required at different stages of maturity).

Early stages need to be populated with manyprojects; late stages often only contain single-digitnumbers of projects. Conversely, projects are ‘cheap’in the early stages, whilst costs increase exponentiallytowards later stages. The long timelines involved inR&D mean that a sequential approach to portfoliomanagement is rarely feasible.

Overall, active pharmaceutical portfolio manage-

Table 1. Example of risk-stratification

Ability to provide early Likelihood Costs ofevidence, or existing evidence of technical Confidence confirmative Overall

for role in human disease success in safety clinical trial risk

Project 1 Low Medium Low High High

Project 2 Medium High Low Medium Medium

Project 3 High High Medium Medium Medium

ment is dependent on a large ‘pool’ of potential andactive projects at various stages in the R&D life cycle(see Figure 1) to allow data-driven terminations,prioritizations or accelerations. Stage gates are used asquality hurdles prior to the next (and increasingly moreexpensive) investment decision. As a project proceedstowards the final stages, its inherent value will increase,whilst its attrition risk will decrease. The number ofprojects in each stage will start to reduce with eachstage, effectively producing a funnel effect, with veryfew, carefully selected, high-cost projects in the laststages.

Figure 1. Generic stages from idea to market

• Nine major ‘gates’ from idea to market• Risk is inherent in each stage and multiplicative• The earlier the stage, the higher the risk• The later the stage, the higher the cost• The earlier the stage, the higher the number of projects required

to ensure one project survives to the last stage.

idea market

Portfolio management in Pharma

Figure 1 illustrates the need for portfolio managementnot only from a project-type perspective, but also froma portfolio dynamic viewpoint. From idea to marketcan take 10 to 15 years, which means the ability to‘parachute’ later-stage projects into the portfolio canadd significant value by shortening time to market, andthrough avoiding some of the earlier attrition stages.

A N N E X 9 D . P O R T F O L I O M A N A G E M E N T I N T H E P H A R M A C E U T I C A L I N D U S T R Y

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Figure 2 is only an illustration, albeit a representativeone, of early attrition, and transit through stage gates.In this example, 10 new ideas, started in 2004, willonly deliver five projects into the second stage withinone year. Overall, it takes four years for these 10 ideasto deliver 1.4 development candidates (CANs). Theprobabilistic nature of this forecast means that 1.4equates to a high likelihood of one CAN and a lowlikelihood of two CANs in 2008.

Figure 3 illustrates that forecasting stage content infuture years from existing projects, based on survivalrates allows estimation of future resource requirements.Active portfolio management will try to ensure overallstage content meets overall output goals (e.g. one prod-uct), whilst ensuring future resource demand is con-sidered.

In summary, pharmaceutical portfolio managementis vital for achieving future success. It is a complex com-posite of:

Figure 2. Forecasting future output from current stagegate content in discovery

Figure 3. Forecasting future resource demands throughdynamic modelling of stage gate transition

• Decisions on which disease areas to work in. Suchdecisions are based on medical need, epidemiology/demographics

• Consideration of technical feasibility• Ongoing data collection to inform early decisions• Costs and time required for reaching decision points• Costs of goods (of the final product)• Required numbers of projects in each stage and their

composite risk profile commensurate with statedgoals (number and types of products) and availableresources.

Portfolio management is an ongoing process, requir-ing frequent decisions/remedial actions to create andmaintain a balanced portfolio that has the highestchance of delivering against stated goals.

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ANNEX 9E

Demonstrating value: Performance metrics for healthproduct development public-private partnerships

Marc Pfitzer (Foundation Strategy Group, Switzerland)

In this paper, we propose a performance frameworkthat goes beyond the usual measures to capture howPD PPPs create value in four ways:

1. Building unique capabilities and platforms to attractand select the most promising projects

2. Improving their partners’ research capabilities3. Mobilizing funds in line with portfolio and organi-

zational developments4. Enhancing knowledge and knowledge dissemination

among research partners and the broader publichealth actors involved in turning new products intohealth impact.1

We further seek to demonstrate the connection be-tween these added-value activities and progress in R&Dand operational costs.

Three levels to performance assessmentDonors and management can assess the performanceof PD PPPs, on three levels, as shown in Figure 1.

Executive summary

Anew and important type of public-private partner-ship (PPP) has emerged in recent years, mobilizing

hundreds of millions of dollars in philanthropic andpublic funds to subsidize the private research and de-velopment (R&D) of new health products to cure orprevent diseases that afflict the world’s poorest popu-lations. Private firms have found that subsidized R&Dcan justify the development of products that bring littleor no expectation of future profitability. Conversely,governments and philanthropists have found thatleveraging the resources and expertise of private firmsworking in partnership with public and academic researchinstitutions can accelerate drug discovery, creating a newgeneration of effective, affordable and patient-friendlyhealth products that can save millions of lives.

In contrast to more immediate health interventions,however, it is extremely difficult to evaluate the effec-tiveness of these health product development (PD)PPPs. Inevitably, the development of new health prod-ucts is a scientifically complex and lengthy process thatconsumes vast sums of funding and offers only uncer-tain prospects of success. Increasing the difficultly ofevaluation, PD PPPs are merely funding intermediar-ies, adding a layer of overhead in channelling donorfunds to targeted R&D projects. To justify their costs,PD PPPs must be able to demonstrate the value theycreate through easily understood metrics of performance.

Developing explicit performance metrics that go wellbeyond the usual reporting of dollars raised and dis-bursed will serve both PD PPPs and the donors thatsupport them. Identifying and tracking the value thatPD PPPs add will encourage donors to sustain theirinvestments over the long term and, simultaneously,focus PD PPPs on the activities that are most likely tocontribute to their own success.

1 These four forms of value creation are derived from theHarvard Business Review article: “Philanthropy’s New Agenda:Creating Value”, by Michael E. Porter and Mark Kramer, co-founders of Foundation Strategy Group.

Level 1

Level 2

Level 3

Direct activities andcosts (R&D)

Indirect and valueadded activities

Operationalcosts

Intermediaryand primary

impact

Registrationof an efficacious,

affordable andpatent-friendly

product

Figure 1

A N N E X 9 E . D E M O N S T R A T I N G V A L U E


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Level 1 indicators track direct progress towards theorganization’s objective. In essence, this first level cap-tures whether the PD PPPs, and particularly the R&Dpartners and projects directly or virtually linked to theorganization, are progressing towards new productsin line with expected milestones and costs.

Level 2 performance measures represent a new per-spective, highlighting the PD PPPs’ primary value-added activities. This is often the missing link inperformance frameworks, and yet an essential one indetermining whether the PDPs are successful in pur-suing activities that more than justify their costs byenhancing the chances for accelerating the success ofR&D efforts.

Level 3 measures assess operational costs in view ofthe value-added activities of the preceding level. Thisthird level allows stakeholders to assess the PD PPPs’project-related and management overhead costs in viewof the extent and value of the activities deemed neces-sary for success – rather than relying on arbitrary levelsof ‘acceptable’ overhead costs.

The following analysis outlines selected elements ofa performance framework for PDPs, without claimingto be comprehensive for any specific organization orproduct.

Level 1: Performance on direct R&D activitiesDeveloping and maintaining a portfolio of projects meetingproduct criteriaBased on industry experience, and knowledge of dis-ease and product-specific attributes, PD PPPs have agood sense of how many compounds will have to bescreened in early discovery phases and/or tested in

subsequent development phases to succeed with at leastone product registration. For new drug development,for example, the number of projects added at variousstages of the portfolio versus the expected numberneeded to result in a final product is a key perform-ance indicator.

Transitioning the R&D projects in line with industry best practicesAgain, based on industry experience, PD PPPs candemonstrate that projects are (not) transitioned intothe next phases of discovery and development basedon best practices and on a clear expectation of howlong it should take the R&D partners to complete thestudies associated with each step and with the particu-lar challenges of the target disease and product. Thesemeasures can quickly point to deviations and mostimportantly, to accelerated projects that are most prom-ising

Achieving competitive costs in R&DWith an understanding of the required studies associ-ated with each phase in the R&D process, PD PPPsshould have a good sense for the cost ranges associ-ated with each phase of each project. These figures,reported across the portfolio, will increase donors’understanding of the total direct project costs of thePD PPP, and the extent to which the PD PPP’s activemanagement has decreased R&D costs, as describedmore fully in Level 2, below.

Level 2: Intermediate measures of progress onadded-value activitiesThe direct measures of success listed above, however,still leave donors and management far short of a totalperformance review for PD PPPs. Equal progress ondirect R&D performance indicators could have beenachieved by funding projects directly, without the in-termediary of a PD PPP. Performance metrics there-fore must also demonstrate how the PD PPPs’ specificadded-value activities have contributed to the directR&D results, as depicted in Figure 3.

Building unique capabilities and platforms to attract and selectpromising projectsPD PPPs can exploit their legitimacy, reach and knowl-edge advantages to mobilize the best projects or projectelements. They are neutral, unaffected by profit mo-

Level 1 Performance on direct activitiesand costs (R&D)• Portfolio of R&D projects meeting efficacy,

affordability and acceptability criteria• Transitioning R&D projects through the

portfolio in line with industry best practice• Achieving competitive costs in R&D

Operational costs

Impact

Indirect and value added activities

Level 3

Level 2

Figure 2

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tives, dedicated to a public health cause, offer the prom-ise of fair contractual terms with partners in all kindsof institutions on a global scale and have access to ex-pert advisors in their respective fields. In reporting onperformance, PD PPPs can demonstrate that they areexploiting these advantages. Superior project selectionis a key area of added value and one that builds on thePD PPPs’ inherent advantage. Project selection in par-ticular may create value towards adding the rightnumber and kind of projects into the pipeline and to-wards creating better prospects for competitivetransitioning.

Key indicators on project selection may include feed-back on the profile of the PD PPP with the relevantscientific community. In turn, the number of projectsproposals resulting from requests for proposals (RFPs),or even better, the number of high-quality/on-targetproposals will indicate whether high awareness is con-verted into concrete initiatives. Additionally, feedbackon the RFP and selection process may provide insighton areas for improvement.

Reporting on the time the PD PPP is taking on av-erage to convert proposals into funded projects willpoint out how well a it is managing (or subcontract-ing), for example, the intellectual property right (IPR)process. Another early indicator of projects’ potentialfor meeting competitive transition rates will be visiblein the nature of the partnerships created. Projects thatintegrate teams from industry, academia and researchinstitutes may have better access to compound screen-ing libraries, scientific expertise, lab infrastructure, etc.

In terms of project selection, in summary, PD PPPscan demonstrate their added value by linking their ac-tivities to their reputation in their scientific commu-

nity, to a continuous supply of high-qualitycandidates and to excellent management ofthe selection and contractual processes.

Improving partners’ research capabilitiesAt the core of much of the PD PPPs’ activi-ties are those that enhance their partners’ ca-pabilities. Success on this level may particularlyadd value to the direct transitioning and costmeasures of progress.

As part of the contractual process leadingto the funding of specific projects, studyguidelines, work plans and milestones are es-

tablished early with the R&D partners. This processserves to focus the efforts on the desired product out-comes and sets expectations for timely delivery on thestudies. The rate of fulfilment on key milestones forprojects and across the portfolio is indicative of disci-pline towards meeting the product objectives. Indica-tors can point to particular studies that are beingaccelerated through the PD PPP’s effort, as a result,for example, of securing fast-tracking conditions withregulatory authorities. Other important determinantsof added value in this area may be the partners’ feed-back on the performance of the scientific or programmeofficers in contributing to their progress. Such feed-back can be mirrored by the officers’ own self-assess-ment and other important internal human resourcesindicators on job satisfaction, staff turnover, etc.

PD PPPs can have a tremendous influence on low-ering the cost of studies through such added-value ac-tivities as outsourcing of project studies, facilitating theentry of new assets to the partnership through sharingof technologies and infrastructure or providing accessto experts or compound libraries. They can also helplocate clinical studies in disease-endemic countries toreinforce both the health impact and the cost objec-tives, and secure in-kind donations from all sectors in-volved (access to infrastructure, technologies, clinicaltrial sites, etc.). While establishing precise estimates ofcost savings may prove too cumbersome, well-foundedestimates can provide stakeholders with a convincingdemonstration of added value.

In short, PD PPPs can demonstrate their added valuein enhancing the capabilities of their partners by indi-cating how their activities have kept portfolio projectsin line with aggressive timelines, accelerated particular

Level 1

Operational costs

Impact

Superiorproject

selection

Level 3

Level 2:Indirect andadded valueactivities

Imptovedpartnershipcapabilities

Newresearchfunding

Newknowledge

Performance on direct activities and costs (R&D)

Figure 3



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studies or R&D phases, contributed to cost reductionswhile maintaining a high level of satisfaction amongpartners.

Mobilizing funds in line with portfolio and organizationaldevelopmentsOf crucial significance for all PD PPPs is the extent towhich they succeed in mobilizing sufficient funds, typi-cally from both private philanthropic and publicsources, to meet the demands of the projects and ofoverheads. This funding gap or surplus, reported forexample as a percentage of total annual needs, as inthe case of Medicines for Malaria Venture (MMV), isan essential indicator of added value. PD PPPs can breakdown these targets by funding sources or segments,and associate fulfilment of fund-raising goals with eachtarget segment. Backing these figures, in turn, mightbe feedback from donors and prospects concerning theventures’ profile, progress and so on.

In essence, the PD PPPs added value on the costdimension is determined by their ability to close thefunding gap and to demonstrate that fund-raising ac-tivities are leading to increasingly informed donors orprospects and to success with specific donor segments.

Enhancing knowledge and knowledge dissemination amongresearch partners and the broader public health actors involved inturning new products into health impactKnowledge development and dissemination, in theform of reports, communications and advocacy cam-paigns, conferences, etc., can be of substantial valuetowards advancing the work of all partners. Yet, link-ing these activities with direct measures of progress isalso likely to prove the most challenging. However,PD PPPs do have a sense of – or seek to research – themajor knowledge or practice gaps that are or mightlimit the partnerships’ progress. Based on these priori-ties, PD PPPs should be able to report how advancesin these areas are influencing both internal and part-ner activities. Disseminated breakthroughs on identi-fying biological targets may stimulate both scientistsand donors, new field information on the disease bur-den, disseminated through the scientific communityassociated with the partnership, may sharpen researchand development criteria. Expert additions to the sci-entific advisory committee may also improve projectselection and review criteria, and so on.

While the focus of this paper has been on PD PPPs’core R&D activities, it is clear that knowledge activi-ties may be most valuable upstream from R&D (forexample, in informing the donor community of theextent of funding required for success), or downstreamfrom R&D (e.g., to inform access partners of emerg-ing breakthroughs and to begin integrating these in-novations into the post-R&D delivery process) toinfluence all other actors involved in turning new prod-ucts into health impact.

PD PPPs, in brief, can demonstrate the impact oftheir knowledge activities on the integration of high-quality projects into the portfolio, on sharpened R&Dstudies based on scientific breakthroughs, and mostimportantly upstream and downstream from R&D, ona better context for R&D and improved conditionsfor product delivery.

Level 3: operational costsOnly now can we begin to address the third level ofperformance around operational costs. Far too often,project overheads are evaluated on the basis of ‘gener-ally acceptable’ levels. In fact, it is only with a clearsense of the nature and scope of the added-value ac-tivities performed by PD PPPs’ scientific staff thatstakeholders can view the direct project support withan informed eye. Reporting total project overheads(covering the scientific teams, advisory councils, R&Dconsultants, IPR fees, etc.) as a percentage of R&D ortotal costs only makes sense if put into the context ofadded-value activities.

As with project-related overheads, it is only withregards to all added-value activities that the other or-ganizational overhead costs become relevant figures.Clearly, a PD PPP with substantial fund-raising andadvocacy activities will have different overhead coststhan a PD PPP that is focused more on the science andmanagement of R&D.

Summary of total performance frameworksfor PD PPPsFigure 4 summarizes select performance metrics thatPD PPPs might therefore employ to demonstrate theiradded value and progress towards product innovations,as a basis for disease prevention or alleviation.

Clearly, for each PD PPP, whether fully focused onR&D activities or more broadly covering health access

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issues, the relevant set of performance measures willdiffer. But the logic of reporting on both direct andintermediary or added-value results should not.

For all PD PPPs, demonstrating clarity of purpose

Portfoliodevelopment

Best practicetransitioning

Cost & riskminimizing

Superiorproject

selection

Improvedpartnershipcapabilities

Newresearchfunding

Newknowledge

•• Profile in thescientificcommunity•• Number ofproposals•• Feedback onselection process

•• Disseminationreach of newscientific findings

■ Number of projectsselected or terminatedby phase versus plan

■ Level of projectalignment with targetcriteria

•• Time fromproposal tocontract•• Number andtype of partnersmobilized

•• Number andimpact of researchcommunity events•• Profile of thescientific advisorycommittee

■ Success rates andstudy duration versusindustry best practiceor plan

■ Project acceleration

•• Number ofprojects on mile-stone objectives•• Regulatory fasttracking impact•• Partnerfeedback

•• Funding gap orsurplus as apercentage of totalannual cost needs•• Results on sub-annual cost needs•• Donor/prospectfeedback

■ Cost per projectsper phase

■ Narrowing of costuncertainty (ranges)

•• Cost savingsestimates perstudies, R&D phaseor portfolio wide

Intermediaryand primary

impact

Registrationof an efficacious,

affordable andpatent-friendly

product

Overhead costs as a percentage of total costs –and breakdown by added value actrivity

Figure 4

through performance measures, which illustrate boththe interconnectivity and added-value in their variousactivities, will undoubtedly contribute to their much-needed success.


ANNEX 9F

The current research-to-development‘hand-off’ process for product concepts/candidate

products and possible improvements in itSolomon Nwaka (Medicines for Malaria Venture) and

Roy Widdus (Initiative on Public-Private Partnerships for Health)

Executive summary

The research-to-development transition refers to theinterface between basic research and identification

of pharmaceutical product concepts or leads that feedinto the development pipeline. Innovative and sustain-able development of pharmaceutical products for ne-glected diseases will increasingly depend on thisinterface. This discussion paper attempts to cover aperceived ‘gap’ and obstacles in the continuum of ac-tivities in product R&D for neglected diseases throughwhich scientific research is ultimately applied to im-prove human health (see Figure 1).

Why the research-to-development gap is importantThis particular gap is important to pharmaceuticalproduct development public-private partnerships (PDPPPs), since they rely on a flow of product conceptsfrom basic research. The flow that feeds their develop-ment pipeline may be insufficient if either there is in-adequate funding for basic research in the relevant areasor if product concepts coming from basic research are

not translated into plausible candidate products whichthey may then develop further. Except for a few PDPPPs that have made some investment in this high-risk area, available PD pipelines are based on identifi-cation and testing compounds from other indicationareas or modification of existing compounds followedby clinical development.

The gap should also be a cause for concern for thosefunders whose support of basic research is driven ulti-mately by the desire to improve human health. If thefruits of their basic research funding are stalled by lackof attention to this gap, they are not fulfilling theirmandate(s).

The discussion generalizes to cover the problem forall pharmaceutical health products, but readers shouldrecognize that there are significant differences in theprocess for drugs and vaccines in particular.

Why the gap existsThe perceived gap in translation of product conceptsinto early candidate products stems from the same

‘market failure’ which stimulated the crea-tion of not-for-profit PD PPPs. However,for the reasons explained below, remedy-ing it may require interventions by actorsother than the PD PPPs. Such actors in-clude the traditional public funding agen-cies, academic institutions in collaborationwith their technology transfer offices,philanthropic agencies supporting bio-medical research, etc.

The nature of the gap can be furtherexplained by examining the differences ininvolvement where a prospective commer-cially attractive market exists, or is absent.

Figure 1. Gaps and obstacles


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Academics lack tools for chemical validationAcademics lack access to chemical libraries

Industrial strategic considerationsLack of financial resources

BIOLOGICAL FILTER

CHEMICAL FILTER

CLINICAL FILTER

Mos

t PPP

s are

her

e

A fe

w P

PPs a

re co

verin

g th

ese

gaps

(exa

mpl

e M

MV)

Targets do not enter formal discovery phase

assessment and clinical trials

Drugs do not reach patients

Candidates do not enter animal safety

Drug

Drug candidates

Leads

Target validation

Targets

ProteinsGenes

GAP

The research-to-development transition where acommercially prospective market exists• Pharmaceutical companies scan basic research and

sometimes invest in specific academic research pro-grammes to establish concept and identify leads forpossible products of interest.

• Those undertaking basic research who can envisagea product with a commercially attractive market, ifso inclined, can create start-up companies, oftenfunded by venture capital or agreements with ‘bigpharma’ to develop the product idea into a candi-date product.

• These efforts are usually supported by dedicatedbusiness development units working with a clear in-tellectual property (IP) mandate.

These factors lead to funding and management of theresearch-to-development transition where some com-mercially attractive market exists.

The research-to-development gap where a commerciallyattractive market does not exist• Pharmaceutical companies are not motivated to scan

basic research or fund ‘upstream’ from developmentsince they would not engage in PD due to the ab-sence of a prospective market. Venture capital orcontracts from pharmaceutical companies are una-vailable to those investigators wishing to pursueproduct concepts arising out of basic research. Mostexisting PD PPPs are focused on developing themost promising candidate products available. Theydesire to demonstrate their effectiveness (to fundersand the general public) as early as possible. Invest-ing in early discovery concepts is unattractive be-cause (a) the ‘time to market’ is likely to be verylong; (b) there is a high risk of failure at these ear-lier stages; and (c) some available collaborators maybe unfamiliar with the activities necessary for proofof concept, and may be reluctant to cede control oftheir ‘invention’ to others and to adhere to rigor-ous deadlines.

• Basic researchers addressing neglected diseases havefewer opportunities to feed product ideas or com-pounds into preliminary screening systems than forcommercially attractive products. In this regard,screens recently established by NIH and under theauspices of TDR are welcome moves in the right

direction. TDR is supporting whole-cell screens atthe Swiss Tropical Institute, London School of Hy-giene and Tropical Medicine, and at the KitasatoInstitute (Japan). A screening facility against mo-lecular targets is now in place in Harvard University(http://iccb.med.harvard.edu) and in Melbourne.The NIH is supporting a team of structural biolo-gists in Seattle, USA.

• For leads that might be identified by industry sci-entists sympathetic to addressing ‘neglected dis-eases’, there is no structured system for referral (forexample, scientists at a major pharmaceutical com-pany have identified possible new agents againstonchocerciasis/river blindness, but lacked a systemto which to ‘hand-off ’ these leads).

• No consistent IP strategy exists for products com-ing out of academic basic research.

• The limited number of R&D-capable pharmaceuti-cal companies in low- and middle-income countrieswhere ‘neglected diseases’ are endemic are unlikelyto view these diseases as attractive investments, giventhey also desire to be profitable. These companiesare happy to participate in R&D for neglected dis-eases but they need financial support and appropri-ate partnership.

• Activities that are more ‘applied’, particularly wherethey involve repetitive or routine screening, aresometimes perceived as less prestigious or innova-tive among academic researchers, and may not com-pete well for awards from basic research funders.One can argue, however, that the overlap of differ-ent technologies and expertise required for this re-search-to-development interface makes some of theearly routine activities less obvious. Some scientificjournals now emphasize applied research and prod-uct development issues. Most academics are morethan willing to help fill this gap (and have expressedstrong desire to do so) but funding is limiting. Typi-cal academic funding is well suited for hypothesis-driven research but moving beyond hypothesis intoapplication would require higher investment forproof of concept and project management. It shouldbe mentioned that the management part of this tran-sition is important.

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How big is the problem? How should it be viewed?These factors point to the existence of a gap and ob-stacle early in the research-development-utilizationcontinuum for neglected diseases. This gap appears tobe significant and could constrain the capacity of PDPPPs to be successful in the long term and be sustain-able. The extent to which existing PD PPPs are beingconstrained by a lack of promising candidate productshas not been (but should be) subject to a systematicsurvey. Anecdotal reports suggest it may be most se-vere in the uniquely tropical diseases (trypanosomia-sis, Chagas disease, and leishmaniasis) and fortuberculosis.

It is possible to identify product concepts forneglected diseases that deserve more resources (e.g.,alternative potentially-cheaper, protein-based pneumo-coccal vaccines) and technologies that might be appli-cable to neglected diseases (e.g., development ofappropriate animal models for drugs and vaccines).

The perceived gap may not be easily quantifiableand may be better viewed as part of a continuum ofactivities that must function adequately for other play-ers also to achieve success:

• Without satisfactory research-to-development hand-off for neglected diseases, basic research funders witha mandate for health improvement will not achievetheir mission

• Without an adequate flow of promising candidateproducts, PD PPPs will be forced to accept scien-tifically less attractive candidates, and their prospectsfor success will diminish

• Without earlier steps in the continuum functioningsatisfactorily, those engaged in disease control pro-grammes will lack effective tools to contribute toimproving the health of populations in poorer coun-tries

• Without adequate investment on the research-to-development interface, neglected diseases will con-tinue to loose out from recent advances in genomicsand technologies such as bioinformatics, high-throughput screening, in silico modelling, X-raycrystallography and the structural determination ofprotein-ligand complexes and combinatorial chem-istry.

What actions might help close the gapActions that could close the research-to-developmentgap can be considered from four perspectives:

• Players currently operating: researchers and fundersin this part of the continuum

• Establishing an understanding of the long-termimplications of this gap for neglected diseases

• New funding mechanism to help fill the gap• The current PD PPPs that are ‘mid-stream’ in the

continuum.

Helping researchers move product concepts tocandidate productsAs noted above, researchers in academia and otherresearch institutions may have difficulty in moving be-yond functional hypothesis and testing their nascentproduct concepts such as novel compounds, potentialtherapeutic targets or ‘designs’ for vaccines.

They may also have difficulty identifying potentialcollaborators with expertise or skills in early productdevelopment who are interested in neglected diseases.

To ameliorate these problems, funders of varioussorts could consider:

• A funding strategy that seeks to support the trans-lation of basic research into early product leads thatwill feed into the development pipeline of PPPs. Thiswould involve targeted collaboration between bi-ologists who have the potential to identify and vali-date targets, structural biologists with the potentialto feed structural information back into productdesign and chemists with access to compounds andthe ability to prepare compounds that can bescreened against targets and in whole cells of thedisease organism. The next big step in the transla-tion of insight gained from genomics of parasiticorganisms into drug leads is to integrate compoundscreening and chemistry into this effort. This willform a good basis for innovative product develop-ment.

• Establishing necessary infrastructure for productconcept analysis within public institutions throughincreased funding support.

• Increased investment in enabling technologies suchas rodent models will provide early filters in pro-gressing projects.

• Whenever possible, encourage interaction between

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academic laboratories and pharmaceutical compa-nies as complementary academic and industrial cul-tures are valuable in establishing product concepts.

• A strategy to integrate researchers in disease-endemiccountries will help build capacity and increase theirparticipation in supporting early product R&Dwhich is currently lacking in most developing coun-tries.

• The recently instituted Gates Foundation/NIHGrand Challenge programme is an important ap-proach targeted at filling part of this gap. Encour-age establishment of dedicated centres withininstitutions for whole-cell and target-based screens,as well as structural work to support early promis-ing programmes.

Helping current players in the research-to-development transition contribute more effectivelyPharmaceutical companies support active networkingto create links across the research-to-development gapfor commercially attractive products.

Systematic linkages between basic researchers onneglected diseases and the PD PPPs interested in thesame diseases have not arisen to any great extent be-cause the PD PPPs are focused on quick results andhave very limited resources for addressing such up-stream, unproven ideas

Those basic researchers that are interested in verify-ing the potential of product concepts as potential can-didate products have access to very few funding sourcesat present. The few PPPs that have activities in thisearly stage research have learnt that this area requiresmore resources and management to make an impact.

Hence, potential solutions include:

• Sponsoring networking between basic researcherson neglected disease and related PD PPPs. A key-stone meeting held in March 2001 focusing onDrugs against tropical protozoan parasites: targetselection, structural biology, and rational medicinalchemistry, and on Malaria’s challenge: from infantsto genomics to vaccines (Science 297, 343–347) isan excellent example of how networking can helpto bridge this gap.

• Establishing a road map or criteria for transitioningbasic research into product concepts for each dis-ease and product area (drugs, vaccines, diagnostics).

• Increased funding for exploring the actual feasibil-ity of product concepts.

• Helping support the establishment of infrastructurefor the feasibility of product concepts in public in-stitutions.

• Encouraging partnerships between investigators,institutions and the private sector.

• Encouraging the participation of developing coun-tries in networking and establishment of partner-ships.

• Integrating a management component to appliedresearch.

• Defining a strategy to handle IPR coming out theprogramme.

Current PD PPPsInitially it may appear as though current PD PPPs aregenerally best positioned to cover the process of mov-ing product concepts from basic research to candidateproducts. However, this may not be practical given thatmost neglected diseases and their PPPs lack activity inthis area.

Most existing PD PPPs have defined their taskswithin the product R&D chain and have geared upwith advisors and staffing accordingly. Most of themare reluctant to fund upstream for the reasons givenabove. Expectations for early delivery are high andfunding for their chosen role is already limited. To addthe responsibility for translation of basic research intocandidate products would add a significant adminis-tration burden to their current tasks.

Initial lessons learned through MMV’s activity inthis area show that moving beyond exploratory earlydrug discovery research is limited by:

• Target validation, compound availability, high-throughput screening, and medicinal chemistryinput

• The lack of a multidisciplinary funding strategy forprojects

• New drug targets in academic labs need strong linksto chemistry, high-throughput screening and man-agement support

• Investment in enabling technologies are importantfor filling this gap

• Academics are willing but funding is limiting• Early interaction between academic researchers and

PD PPPs is important.

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References and additional reading1. Nwaka S, Ridley R. Virtual drug discovery and de-

velopment for neglected diseases through publicprivate partnerships. Nat. Rev. Drug Disc. 2003, 2,919–928.

2. Towse A, Mestre-Ferrandiz J, Renowden O. Esti-mates of the medium-term financial needs fordevelopment of pharmaceuticals to combat ‘neglecteddiseases’. Prepared for an IPPPH Workshop, heldon 15–16 April 2004, London, UK.

3. Gelb MH, Hol GJ. Drugs to combat tropical pro-tozoan parasites. Science, 2002, 297, 343–344.

4. Long CA, Hoffman SL. Malaria-from infants togenomics to vaccines. Science 2002, 297, 345–347.

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ANNEX 9G

Ethical review capacity: Country needs, role andresponsibility of partners and researchers

Rose Gana Fomban Leke (University of Yaoundé 1, Cameroon)

search partnerships are beneficial to both parties andto the community, and should be encouraged, collabo-rations sometimes lack good research practices. It isessential that those who fund and sponsor researchdevelop real partnerships with researchers in develop-ing countries. True partnerships will ensure all-roundcapacity strengthening for these developing countryinstitutions, which will then make the most efficientuse of resources to attain the objectives.

Setting up ethical review committees in Africancountries that do not have one is urgently needed, asis training the members of these newly established com-mittees on the review process. Where the committeesdo exist, it is also important to strengthen their re-view-process capacity among their members. Bodieslike AMANET, which is already very active in strength-ening the capacity of these committees, the Pan-African Bioethics Initiative (PABIN) and the AfricanHealth Research Forum (AHRF) should be furthersupported in their efforts.

The ethics of health research in African countrieshas been of great concern, and increasingly deservesmuch attention. This is even more critical today withthe increasing, devastating effects of HIV/AIDS, on-going interest in vaccine research and development,and advances that have and are being made in newtechnologies and in genomics. There is a trend for in-creased funding for research in Africa and the conti-nent, with its multiplicity of endemic infections andincreasing disease burden, is now fertile ground forclinical trials of drugs and candidate vaccines, and forepidemiological studies. Although there is still an ab-sence of a research culture, the importance of healthresearch as a tool for development is recognized. In afew countries, institutions have been set up and arenow involved in health research, although their research

Executive summary

The ethics of health research in African countries hasbeen of great concern, and increasingly deserves

much attention. This is even more critical today withthe increasing, devastating effects of HIV/AIDS, on-going global interest in vaccine research and develop-ment, and advances that have and are being made innew technologies and in genomics. There is a trendfor increased funding for research in Africa. The conti-nent, with its multiplicity of endemic infections andincreasing disease burden, is now fertile ground forclinical trials of drugs and candidate vaccines, and forepidemiological studies. Although there is still an ab-sence of a research culture, the importance of healthresearch as a tool for development is recognized. In afew countries, institutions have been set up and arenow involved in health research, although their researchinfrastructure is weak and they lack the critical mass oftrained and devoted research scientists.

Some African countries still do not have an ethicalreview committee (Institutional Review Board). Othercountries have recently set up such a committee, butonly because its establishment was a pre-requisite for aclinical trial planned for the country. Of the Africanethical review committees that exist, some functionwell, most are mediocre, and in some countries thescientific committee does both jobs. Most members ofexisting committees do not have access to standardinternational guidelines, and have not had any train-ing in following and interpreting them. In cases whereinformed consent is sought, much more awareness-rais-ing, education and communication are needed to makethe process of obtaining true consent credible.

Research, and health research in particular, is almostcompletely dependent on external funding due to in-sufficient national investment in this area. Whereas re-

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infrastructure is weak and they lack the critical mass oftrained and devoted research scientists.

National investment in health research is insufficientand the private sector in Africa is not involved as apartner in research funding, so institutions are com-pletely dependent on external funding. Health researchoften does not address the country’s priority healthproblems, either because research projects have notbeen set up by the country itself or because the re-search is sponsor-driven. Partnerships are rarely an as-sociation of equal parties, but rather a donor–recipientpartnership. For these, and for many other, reasons,health research ethics require much more emphasis andan urgent need is seen for a valid and functional regu-latory framework in each African country.

This paper will focus on some aspects of ethics inhealth research that need urgent attention.

Ethical review committeesSome African countries still do not have an ethical re-view committee (Institutional Review Board). Othercountries have recently set up such a committee, butonly because its establishment was a pre-requisite for aclinical trial planned for the country. Of the Africanethical review committees that exist, some functionwell, most are mediocre, and in some countries thescientific committee does both jobs. Most members ofexisting committees do not have access to standardinternational guidelines, and have not had any train-ing in following and interpreting them correctly. Al-though existing international guidelines and regulationsshould be considered generic, it must be emphasizedthat they were developed mainly by non-African na-tions and have not taken into consideration culturaldifferences that may exist.

The African Malaria Network Trust (AMANET),1

Pan-African Bioethics Initiative (PABIN), AfricanHealth Research Forum (AHRF) and other interna-tional bodies have been involved in efforts to helpstrengthen capacity for health research ethics on thecontinent. AMANET has organized six training work-shops in capacity building for African scientists in healthresearch ethics. The National Institutes of Health, USA,has also organized similar workshops in various

countries in Africa. AMANET and PABIN jointlyorganized one of these workshops specifically for chair-persons and secretaries/administrators of ethical com-mittees in February 2003 in Entebbe, Uganda.Participants came from ten African countries. But thecontinent has 46 countries… So, many more suchworkshops are needed, along with a set curriculum, toensure that committee members acquire some compe-tence and skills to enable them to provide ethical guid-ance in health research in their various countries.

AMANET has also organized and run many work-shops on Good Clinical Practice (GCP) for Africanresearchers, and plans to hold more workshops in thefuture depending on available funding. The AHRF isworking on an inventory of existing committees; it thenintends to find ways of establishing them where theydo not exist. Due to lack of funds, however, the projecthas not been able to progress as well as planned. Asregards funding, it is important to note that in manycountries, ethical committees cannot meet with othersto review grants because members receive no fundingto cover their travel costs to the proposed meeting lo-cation. In some countries, committees may be given acertain sum (about US$100) per project, but this isoften not sufficient to cover transportation costs forall committee members. This lack of remuneration isdemotivating for members, who may already have manyother reasons to feel frustrated. The funding shouldbe available so that members are encouraged to par-ticipate fully in these meetings.

Informed consentInformed consent means the participants in a researchproject/ clinical trial have been well informed aboutall the advantages/risks involved in the process; thatthey fully understand and give their consent. In theAfrican context, being well informed is sometimes veryrelative. Many participants can neither read nor write.They often do not understand English, French, Por-tuguese or Spanish, and so are dependent on transla-tors/interpreters to explain the process to them; suchinterpretation has its own constraints. How true, there-fore, is the ‘informed’ consent that the participant hasgiven? Even if people living in a village where a studyis to be undertaken receive a thorough explanation ofthe procedure and understand that consent is required,they may feel ‘obliged’ to give their consent because,1 See AMANET website: www.mnet-trust.org

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given the enormous lack of medical personnel and care,they may fear that they will get ‘lower-quality’ treat-ment than those taking part in the study. So they give– perhaps half-heartedly – their consent. Getting trueinformed consent is not always successful, due to lackof understanding and/or education, and is a constantpreoccupation. Another problem in the African con-text is that consent is very often required not only fromthe individual adult participant, but also first from thechief or village head and then the family head. If eitherof these people refuse, it will be difficult for the indi-vidual to consent even if he or she wishes to do so.Information, education and communication have tobe greatly improved to get true informed consent.

Collaboration and partnershipsResearch partnerships are beneficial to both parties andto the community and should be encouraged. Collabo-rating with partners, however, sometimes lacks goodresearch practices.1 Research should be designed tobenefit the participant, the community and the nation,but this is not always the case in research partnerships.The sponsor is the donor and sets the tune. But whoowns the research is not always determined. Initially,both parties should agree on – and adhere to – theterms for the collaboration. Any changes should bemade only after mutual agreement. In true collabora-tions, the terms should include establishing in the de-veloping country better means of communication,information and data access; authors’ rights (whichshould be respected) and intellectual property rights(IPR) on the results of collaborative research. As re-gards IPR and when publishing the results of research,both parties must agree on the list of authors and theposition they are allocated in the manuscript accord-ing to their contribution. Also, in true collaborationsand partnerships, the financial benefits for the investi-gator and staff of the developing country should belooked into. It is very common to find expatriatesworking in a developing country on the same job as anational, but earning five to ten times more. Salariesin developing countries are very low and are the maincause of the ‘brain drain’ that has robbed Africa of mostof its qualified scientists. The poverty of researchers,

research participants and research institutions, includ-ing members of the regulatory bodies, could influenceethics review. African scientists who choose to work intheir counties should be given a salary supplement, sothat they can concentrate on research rather than tak-ing on additional jobs so that they have enough moneyto support their families. Taking all these points intoconsideration when setting up a research partnershipwill ensure true collaboration.

Responsibility of researchers and sponsorsMany new global initiatives exist that promote healthresearch for development. At present, they are the mainbodies funding/sponsoring health research in devel-oping countries. They are responsible for ensuring thatthe capacity to carry out research of local institutionsis strengthened, so that they can provide service andbenefits to the local community. By supporting capac-ity building, the sponsors would be providing, as partof the whole process, the right regulatory frameworkfor the pursuit of health research in poorer nations.

Researchers and sponsors should make sure that adrug to be tried out in a community is one that will bebeneficial to the community after the trial and also thatit will be made available to the participants after a suc-cessful trial.

AccountabilityThe African researcher has a dual responsibility whenit comes to accountability. Firstly to manage projectsby accounting for all funds provided, and then to givefeedback to the village or town on the results obtainedby working in their community. African countries areknown for their competence in mismanaging funds.So credibility in managing research funds is often ques-tioned. African scientists therefore have the responsi-bility to show the world that they can be relied on asfar as accounting for research funds is concerned. Thisis really urgently needed so that funds destined forhealth research on the continent can come directly andbe managed by credible African research leaders andmanagers. AMANET is one of such bodies that is al-ready setting the pace, and is presently funding a clini-cal trial in Burkina Faso, in partnership with Europeanfunding agencies.

1 International Conference on Health Research for Development.Conference Report. Bangkok. 10–13 October 2000.

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Way forward for health research ethics in AfricaThere is an urgent need to locate countries in Africawith no ethics review committees.1 Where committeesexist, review process capacity needs to be strengthened,by training all members of the committee, and ensur-ing that they have the expertise and confidence inworking efficiently as members of the review board.Some financial allocation for these committees is re-quired for proper functioning. At the workshop hostedby AMANET and PABIN, the accreditation of theseethics review committees was discussed. While exactstandards for accreditation will have to be developed,only committees that function correctly will qualify foraccreditation. Standard international guidelines will alsohave to be adapted taking into consideration the socio-

1 Global Forum for Health Research, Forum 6, Arusha, Tanza-nia. November 2002.

cultural differences of the continent, and in individualcountries. In all of this, true success will depend onthe development and sustenance of strong and dura-ble partnerships between interested and committedparties.

A research culture is urgently needed. Education inthis line must be given sufficient attention. Communi-ties need to be educated on the importance of healthresearch for development, as well as on the ethics ofhealth research.

African research scientists working in Africa shoulduse all the opportunities available to foster good ethi-cal practices and ensure that all financial and regula-tory exigencies in carrying out research projects aremet.

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ANNEX 9H

Current status of clinical trials in AfricaEbi Kimanani (International Biomedical Research in Africa [IBRIA], Kenya)

and Vaila Clements (Quintiles, USA and South Africa)

The Medicines for Malaria Venture (MMV) has 17products in the discovery and development pipelinewith three in exploration, four in lead identification,five in lead optimization, three in phase I and two inphase III. The Malaria Vaccine Initiative (MVI) hasseveral development projects with a few in clinical test-ing stage in Africa.

These organizations have to find sites to clinicallytest products under regulatory and ethical require-ments, find resources to manage the clinical data andprovide biostatistical analysis of the data. At present,each sponsoring organization develops or finds theseservices independently from others with similar inter-ests. IAVI has a vigorous site development approachstarting with extensive feasibility and preparedness stud-ies in potential testing locations. A significant portionof the activities of the Aeras Global Tuberculosis Foun-dation involves clinical site development designed toenhance the capabilities of physicians, scientists andpublic health workers in TB-endemic areas, the West-ern Cape region, South Africa being one example.Among testing sites for MMV products are those rep-resented in the portfolio of programme developmentpartners for the specific project. For the immediateneeds of the sponsor organization, this solo approachto site development will serve its purpose since it isdesigned to optimize specific site capacities for thesponsor’s needs.

However, the disadvantages to this approach includehigh per capita cost and potential site competition.Moreover, because such an approach primarily focuseson trial-specific requirements, more institutional-specific development issues may be overlooked, suchas appropriate Institutional Review Board (IRB) over-view and health authority intervention in ensuring pa-tient safety. Most importantly, no safeguards prevent

Executive summary

Diseases of the developing world’ have been the fo-cus of increasing interest from governmental and

non-governmental organizations, the pharmaceuticalindustry and non-profit organizations such as the In-ternational AIDS Vaccine Initiative and Medicines forMalaria Venture. A key catalyst to the non-profitefforts at bringing affordable drugs and vaccines toresource-constrained regions has been the Bill &Melinda Gates Foundation which alone has providedover US$3 billion to global health care initiatives, US$1billion of which has been for research in infectious dis-eases. The United States’ National Institutes of Healthand the European Commission have also committedbillions of dollars into research in malaria, tuberculosis(TB) and HIV/AIDS. On the industrial front,GlaxoSmithKline, Novartis and AstraZeneca are alsoinvesting both human and financial resources in thesediseases.. Furthermore, there are over 300 productsbeing developed for HIV, 45 for malaria and 22 forTB. A gap exists between products in development andthe current capacity in sub-Saharan Africa for variousphases of clinical trials necessary to support this prod-uct pipeline. In this paper, we review some areas ofinadequacies and suggest some ways forward.

Clinical trials pipelineIn response to the global call for more attention andresources to be given to diseases of poverty, a numberof organizations and pharmaceutical companies haveinvested resources in R&D for more medicinal prod-ucts for infections endemic in developing countries.The International AIDS Vaccine Initiative (IAVI) hasan ambitious goal for the decade 2000–2010: to de-velop up to 12 novel vaccine candidates and advancethe best of them to final phase clinical trials by 2007.

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most – if not all – of these services being contractedand dispatched to the northern hemisphere especiallyby organizations for whom site development may notalways be a primary goal. Pharmaceutical innovatorcompanies, for example, do not typically invest in sitedevelopment, rather they will identify fully capablecentres or entrust a contract research organization fortheir later-phase testing programme. For most of theseorganizations, the primary concern of product discov-ery and development is daunting enough without be-ing required to take on such a significant additionalresponsibility as developing generic infrastructure atstudy locations. Therefore, the essential task of build-ing capacity in the endemic regions to support later-phase clinical trials per se will be most effective ifcoordinated by a separate body.

The current status of clinical trials in AfricaPreliminary investigations1 into the current status ofclinical trials in Africa pointed to some priority areasthat need immediate attention. These are presentedbelow.

A framework for clinical trials existsHealth-care providersOf the 166 health-care providers who responded to asurvey on the current status of clinical research in EastAfrica, 68 per cent had university training in a medicalor biomedical field and 32 per cent were clinical offic-ers with certification from other medical training in-stitutions. Clinical officers are often those in maincontact with patients and in many rural areas are thesole providers of medical care. Hence, it is importantto have information about these professionals, as theywill be involved at some level in clinical trials when-ever non-urban locations are included as research sites.Fifty-two per cent of all participants had additionaltraining in clinical research such as good clinical prac-tice (GCP). All respondents expressed a desire for fur-ther training in aspects of clinical trials and a stronginterest in collaborating with other regional and inter-national researchers. This availability of keen, motivatedand qualified health-care professionals represents a sig-

nificant advantage for those working to develop hu-man resource and other essential systems.

Hierarchical health-care delivery systemsIn most African countries, national health deliverysystem follows a hierarchical structure, with nationalreferral hospitals at the top level, followed by provin-cial or regional hospitals, district hospitals and finallycommunity health centres. The latter represent the firstcontact point with the population. In parallel to thisare private health providers ranging from village homeconsultants to well-qualified specialist physicians , somewith research experience. When setting up a clinicaltrial, the sponsor has to take into account the fact thatthe investigator site will provide basic medical care. Atthe same time, this provides an opportunity to use theframework for health delivery as a vehicle to install clini-cal trial infrastructure and systems such as regulatoryand ethical review systems. Many countries such asKenya, Uganda, Tanzania, Nigeria and others are in-deed using this structure to institute national ethicalreview committees and research guidelines. Protocolsapproved at the national level can be conducted in anyof the hospitals or clinics at the lower strata.

Research networksResearch networks are a collection of sites in variouscountries with a common function. One example isthe African Malaria Network Trust (AMANET), whichis a collection of about 30 institutions in 20 countriesall carrying out some level of malaria research (seeAppendix 1, Figure 1 for locations of sites and Table 1for key to the map). Collectively, the network has about600 scientists at undergraduate, doctoral and physi-cian level, 70 per cent of whom are nationals. It hasbasic and non-uniformly distributed equipment andminimal experience with clinical trials. However, thenetwork is keen to enhance the collective infrastruc-ture for clinical trials in order to meet a significantportion of the looming demand for sites as adhered toin the introduction.

Another major research network is INDEPTH withabout 30 sites in 16 countries involved in long-termintensive demographic surveillance systems (DSS). Bytheir very existence and access to a rich base of longi-tudinal population data through their communities,all INDEPTH sites have basic infrastructure and a high

1 Kimanani EK. Good Clinical Practice in East Africa: Call for aregionally harmonized ICH GCP guideline. East African Medi-cal Journal, October 2001, pp549–554.

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potential for clinical trials. In particular, the networkhas tremendous marketable resources for clinical tri-als, namely, access to participants in highly malaria,tuberculosis and HIV/AIDS endemic communities.The network is in the process of developing a healthintervention platform, which will primarily focus onassessing and classifying sites, developing the capacityand brokering for clinical trials for member sites. Intheir initial phase of this platform, 10 INDEPTH siteshave expressed an interest and are actively working onthe platform for the network. These have been indi-cated in Figure 1 and Table 1 in Appendix A.

In summary, while a skeleton framework for clinicalresearch exists, it must be noted that much of the re-search conducted to date has been either academic-driven projects or epidemiological surveys, few of whichhave been run to serve a regulatory purpose. The fo-cus of future research projects needs to be undertakenwithin the framework of product license applicationsto regulatory health authorities.

Political will towards clinical trials exists but is distractedGovernments in the region have shown initiative to-wards promoting clinical research by setting up researchinstitutions with the general mandate to carry outmedical research to influence public policy. Examplesof these institutions are the National Institute for Medi-cal Research in Tanzania, the Joint Clinical ResearchCenter in Uganda, the Kenya Medical Research Insti-tute in Kenya and the National Institute for Pharma-ceutical Research in Nigeria. These institutions havebeen responsible for raising the general public’s aware-ness of the advantages of clinical research, for provid-ing venues for local scientists to pursue clinical researchinvestigations and for influencing public policy to someextent. More significantly, African leaders have pledgedtheir political will and platforms for promoting andcreating social, political and economic environmentswhich can boost creativity and support all efforts toalleviate poverty. Health in general and in particular,creative initiatives and research activities targeting thethree leading killer diseases, HIV/AIDS, malaria andTB, have been identified as priorities. A commitmenthas been made in the New Partnership for Africa’sDevelopment (NEPAD)1 manifesto for individuals andgroups to come up with ideas and ways for researchinto the alleviation of these diseases.

Non-urban areas are isolatedMedical practitioners in remote areas who have thepotential and are keen to enter into the field of clinicalinvestigation feel isolated from the core of clinical re-search, facilities, funding and decision-making. Accord-ing to such practitioners, almost all clinical studiescarried out in their countries take place in just one ortwo institutions usually located close to the nationalcapital. While these experienced sites run the risk ofbeing overwhelmed, the potential of more remoteareas remains untapped. In these areas, patient popu-lations have little or no access to care and attentionand would therefore be desirable for clinical studiesbecause they are treatment-naive. Moreover, there is aneed to expand clinical research infrastructure beyondexisting, experienced institutions.

Inadequate facilitiesFacilities for handling and managing clinical trial dataare minimal at best, especially relative to global stand-ards. When they exist, subject screening tools, facili-ties and biological sample handling laboratories arelimited to research institutions (usually no more thanone in each country), medical training institutionshospitals (at most three per country) and national hos-pitals (again usually one per country). Data processingand reporting are almost entirely handled by the spon-sor, typically from outside the continent.

Inadequate travel and communication infrastructureLogistics involved in conducting clinical trials in sev-eral sites in the region present difficulties, but thesecan be overcome. As in most developing countries,transportation and communication issues remain chal-lenging. However, there are good air connections be-tween major international cities, although travel by airis less dependable within each country. Roads to mostof the remote areas are good enough for a reliable ve-hicle. Communication in most areas is possible by cel-lular phones. The pledge of government leaders tosupport clinical research in general will help to createlogistically viable environments.

1 The New Partnership for Africa’s Development (NEPAD). Thefirst core document, 2001. http://www.touchtech.biz/nepad/files/en.html



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Significance of cultural factorsCultural factors are still significant issues to be consid-ered when planning and conducting clinical trials inAfrica. As long as a study is seen to be from the ‘out-side’, acceptance and cooperation may not be as forth-coming as may seem on the surface. Site developmentcovers a multitude of activities, the basic foundationfor which needs to comprise social and ethical accept-ance that clinical trials are positive for the people.Health-care clinics, local religious and community lead-ers, etc., need to give studies a favourable receptionfor such acceptance to be forthcoming. So, essentialsystems should be built from the ground up, allowingenough time for the systems to be rooted in goodwilland earn the trust of all local players. Community Ad-visory Boards (CABs) are a good start in this regard.Their role is to promote communication between thesponsor, the research team and the community of trialparticipants and ensure that community leaders areinformed about the protocol, buy in to the trial andhelp with logistics and follow-up of the study.

Dependency on outside fundingCurrent methods of sponsoring studies do not fosterself-sufficiency and capacity building. The reasons aremulti-factorial but may be largely due to the lack ofindigenous drug development, lack of financial re-sources, insufficient political support and unclearlycommunicated missions and motives of the sponsors.Including Africa as an authentically feasible, viable andsustainable partner in global drug development hasmany significant advantages that may not be immedi-ately monetary. Articulating these advantages andbuilding capacity to support later-phase clinical trialswould best be fostered by an independent organiza-tion situated in Africa which has credibility on bothlocal and international fronts. The role of such an or-ganization would be to serve as a link between Africaninstitutions and the affected people, and the clinicaltrial sponsors with sustainable milestones on local self-sufficiency.

Way forwardWhat targets do we set?In order to meet the prospective demand for clinicaltrial capacity it is necessary to set some targets. Themost basic and achievable targets for the next decadeare, for example:

• Regionally harmonized clinical trial guidelines• International Conference on Harmonization (ICH)

compliant IRBs to ensure both ethical and safe clini-cal research in a number of African countries

• Clear accessible health research requirements basedon regulations

• A threshold level (say 50 per cent) of local capacityto support a wide range of clinical trials.

How do we get there?The workshop on clinical trials capacity in low- andmiddle-income countries1 highlighted some areas thatneed urgent attention and outlined some minimumrequirements for an entity such as proposed above.Briefly, these are presented below.

• Building infrastructure and capacity for clinical tri-als is a multifaceted and expensive challenge but ab-solutely essential. Hence most urgent is the call forleadership in capacity strengthening.

• Committed and compassionate scientific and politi-cal leaders are needed in order to advocate for andmanage clinical trials.

• Material and financial support will be needed toenhance basic infrastructure, general training of clini-cal trial support personnel with particular attentionto GCP and publicity of research sites through, forexample, a regularly updated database of clinical trialinvestigators and sites, preferably Internet based.

• Investigators and research sites will need to workon research governance structures.

• This means entering into dialogue with the rightgovernment offices that regulate clinical trials so thatthese are communicated clearly to those that are in-volved in clinical research. It also means institutingscientific and ethical review committees accordingto local and international regulations is critical.

• There needs to be relevant, self-regulating andadaptable systems for administration, project man-agement, study conduct and site audit.

1 Clinical trials capacity in low- and middle-income countries:Experiences, lessons learned and priorities for strengthening,Meeting Report by the Initiative for Public-Private Partner-ships for Health, 2004. http://www.ippph.org.

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RecommendationsWe end this paper with two recommendations to beconsidered by PD PPPs and funders.

• Many components for clinical trial support and fa-cilitation are common to multiple disease areas andtheir interventions. It would be worthwhile for PDPPPs to consider some common platforms for build-ing the capacity to realize these cross cutting ca-pacities.

• We feel that for many reasons such as those discussedabove, PD PPPs’ African partners should spearheadclinical trial facilitation in Africa.

AcknowledgementsWe are grateful to Roy Widdus for providing the di-rection for this paper. Discussions with Dr ChrisWebber, MD, Dr Willie Conradie, MD, Ms SorikaVannieker and Dr Annalene Nel of Quintiles provideda useful contract research perspective in site develop-ment.

APPENDIX A

Table 1. Names of sites shown in Figure 1

Key Country Site Network Remarks

1. Senegal Institut Français de Recherche Scientifique AMANET Malariapour le Développement en Coopération,Centre ORSTM de Dakar

2. The Gambia Medical Research Council Laboratories, AMANET MalariaBasse Field Station

Medical Research Council Laboratories, Fajara

Farafenni INDEPTH Farafenni is a small town on the north bank of theThe Gambia River about 170 km from the capitalBanjul. The surveillance site is located in a rural areaand comprises 40 small villages.

3. Côte d’Ivoire Pierre Richet Institute AMANET

4. Burkina Faso Centre National de Lutte contre le Paludisme AMANET Malaria(CNLP) Muraz Centre

Centre de Recherche en Santé de INDEPTH CRSN is located in the Nouna health district in north-Nouna (CRSN) western of Burkina Faso. The research area includes

about 55 000 inhabitants settled over 1 175 square km.

5. Togo National Malaria Control Program, Ministry AMANETof Health

6. Benin Regional Center for Entomological Researches AMANETof Cotonou

Figure 1. Location of INDEPTH (DSS) and AMANET(malaria) sites in Africa


AMANETINDEPTH

17

20

18

16

19

15

13

14

12

10

11

21

957

86

3

421


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Table 1. Continued

7. Nigeria Cellular Parasitology Program, Ministry of Health AMANET

8. Niger Research Center for Meningitis and AMANETSchistosomiasis

9. Cameroon Organisation de Coordination pour la Lutte AMANETcontre les Endemies en Afrique Centrale (OCEAC)

10. Gabon Centre International de Recherches Médicale AMANETde Franceville (CIRM)

11. Ghana Navrongo Health Research Centre AMANETINDEPTH

12. Sudan Blue Nile Research and Training Institute (BNRTI) AMANET

13. Ethiopia Jimma Institute of Health Sciences AMANET

Butajira INDEPTH The DSS was started in 1987 with a population of28 000, which has now grown to over 41 000.

14. Uganda Med Biotech Laboratories AMANET

Rakai INDEPTH The Rakai project is situated in the Rakai district insouth-western Uganda. The DSS covers 320 square kmand a population of about 45 200.

15. Kenya Kenya Medical Research Institute, Kilifi Unit AMANET

16. Tanzania Amani Medical Research Centre AMANET

Institute of Public Health AMANET

Magu INDEPTH Magu is located in Magu district, in Mwanza region ofnorth-western Tanzania. The DSS area covers 6 sixvillages.

Ifakara Health Research and Development AMANET Ifakara’s DSS includes 25 villages of in Kilombero andCentre INDEPTH Ulanga districts, in Morogoro region in, south-western

Tanzania with a population of about 67 000.

17. Mozambique Instituto Nacional de Saude AMANET

Manhica INDEPTH Manhica site is located in Maputo province in southernMozambique. The DSS population is about 62 000.

18. Zimbabwe Blair Research Institute AMANET

19. Zambia Tropical Disease Research Centre AMANET

20. South Africa National Malaria Research Program, Medical AMANETResearch program

Agincourt INDEPTH Agincourt is located 500 km nNorth-east of Johannes-burg in the Bushbuck region. The DSS covers 21 villageswith a population of about 67 000.

Africa Centre INDEPTH This DSS is located in northern KwaZulu-Natal, SouthAfrica with a population of about 11 000 households.

21. Guinea Bissau Bandim INDEPTH The study area comprises five suburbs of the capitaland a mobile rural unit. It covers a population of about100 000 inhabitants.

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ANNEX 9I

Emerging lessons in preparingfor uptake of new vaccines

Gargee Ghosh (Center for Global Development, USA)1

tries had introduced Hib. The cost of this approachhas been estimated in hundreds of thousands of pre-ventable deaths.2

Current attempts to prepare for introduction of aMeningococcal conjugate vaccine, an HIV vaccine,rotavirus and pneumococcal conjugate vaccines usedifferent approaches, but all attempt to create and sig-nal credibly more predictable demand3 for vaccinesbefore (sometimes long before) products are ready formarket. These PPPs hope that enhancing demand willinfluence not only the timing and rate of uptake oncea product is available, but also the suitability of theproduct being supplied (e.g. profile, price) and thesupplier landscape itself (e.g. number of firms, devel-oped versus emerging suppliers).

Other initiatives in the vaccine community, such asthe Pull Mechanisms Working Group, may offer addi-tional demand-creation tools for PPPs to incorporatein their strategies. By guaranteeing financing for a prod-uct not yet on the market, pull contracts may mitigatedownstream market risk to encourage PD and assuresupply.

Emerging lessons for today’s PPPs are both intui-tive and important. A product introduction strategy isa critical part of a product development strategy. Lackof the first may actually inhibit the latter, so planningfor introduction must begin early. Planning for intro-duction is not just about understanding epidemiologi-

Executive summary

Public-private partnerships (PPPs) are a potentially‘win-win’ approach to speeding the availability of

new products for the poorest of the poor. They helpmitigate industry’s risks associated with commercial in-vestment in global health products in exchange for ac-celerating development and/or securing access. Manyof today’s PPPs see the most direct route to this goalas mitigating upstream risks for biotechnology or phar-maceutical companies by providing direct ‘push’ fund-ing for scientific research, clinical trials or licensure; assuch they are focused on funding and managing in-creasingly complex product development (PD) port-folios. But in this exclusive (or overwhelming) focuson PD, PPPs may be defining their mission too nar-rowly and in a sense not preparing for their own suc-cess – adequate plans will not be in place for what todo when a product becomes available. Instead, PPPsshould develop a parallel track of thinking and prepar-ing for introduction, starting today. This parallel agendashould be part of the strategic plan for all PPPs in-volved in new product development, but will becomeincreasingly important (and urgent) as a productemerges in the development pipeline.

The vaccine world is on a learning curve when itcomes to preparing for the introduction of new prod-ucts. Its recent and current efforts may offer some les-sons for PPPs involved in the development of a widerange of global health products. The historical approachto developing an introduction strategy has been to startthinking about it only after the product is available. Ahepatitis B (HepB) vaccine was introduced in the de-veloping world in the late 1980s, nearly 10 years afterthe developed world; the vaccine for haemophilus in-fluenza type b (Hib) has a similar story. By 2001, 126countries had introduced HepB vaccine; only 77 coun-

1 Global Health Policy Research Network at the Center for Glo-bal Development, 1776 Massachusetts Avenue NW, Suite 301,Washington, DC 20036, USA. Email: [email protected]

2 GAVI estimates that in 2001, 521,000 people died of HepBand 450,000 died of Hib. See GAVI website www.vaccinealliance.org

3 Demand in the case of vaccines incorporates willingness to usewith ability to use and ability to pay (or find funding). Fromtelephone conversation with Alan Brooks.

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cal need; it requires an integrated package of activitiesincluding demand creation through marketing, com-munication and education; credible demand estima-tion; financial planning; and procurement strategies.These activities must be undertaken with an eye onthe long-term objective – product introduction is nota goal in itself, but must be done as a first step to achiev-ing sustainable public health impact in a mature mar-ket. PPPs are well placed to play a critical role in thiswork – they should already embody global expertiseand energy around a particular effort. But PPPs todaydo not necessarily have the right skills – or budget – inplace to take on this task. Preparing for uptake requiresa different set of skills than product development port-folio managers; expertise analogous to a commercialproduct launch team must be built to complementexisting skills and be dedicated to the task. And nomatter what their internal capacity, PPPs cannot dothis alone – they must in the end motivate others toact as well.

Preparing for uptake is a significant task to place onthe shoulders of already overburdened PPPs. Even inthe best of circumstances with all resources in place,bringing new products to market is a risky business.For public goods like vaccines, in resource-poor de-veloping countries with shifting priorities and politicaltradeoffs, and with complex public sector donors, thetask is all the more difficult. But preparing for intro-duction is central to the ultimate success of the PPPs’enterprise and far too important to be ignored anylonger.

This paper is divided into three sections:

• Defining the problem• Approaches to the solution• Emerging lessons.

Defining the problemDespite all evidence pointing to their life-saving powerand their overwhelming cost-effectiveness, vaccines areoften not used to the extent they could be in the de-veloping world, are not supplied to the extent they areneeded or are not even created in a form that meetsthe needs of those who need them most.

Why is the vaccine market failing the developingworld? Vaccines are extremely risky and costly to make,and commercial suppliers often see developing world

vaccine markets as high-risk and low-reward becausedemand is unpredictable and prices are low.1

For mature vaccines, demand can be unpredictableas need, distribution capabilities and national priori-ties change. Uptake of new vaccines can be slower thananticipated if individuals and governments do not un-derstand the benefits of vaccination in general, let alonethe value of a particular vaccine. This results in fore-casts and procurement awards that can be wildly dif-ferent from actual offtake.2

For all vaccines, the ability to pay is an overwhelm-ing constraint on market demand. Traditional vaccines– like diphtheria-tetanus-pertussis (DTP) combinations– sell for very little per dose, and until recently therehad been little reason to think that would change fornew vaccines.3 The existence of the Global Alliance forVaccines and Immunization (GAVI) and the VaccineFund (VF) creates an important opportunity to workwith industry in a new way, but this opportunity hasnot yet been fully tapped.

In this context, PPPs charged with the mission ofreducing burden of disease in a neglected area face acomplex challenge. PD is critical, but it is not enough.Product development without a parallel plan for un-locking some of the constraints on demand (ability touse, willingness to use and ability to pay) has criticalconsequences. When a product is available, years canbe lost developing, negotiating and financing a strat-egy. The opportunity to save lives is wasted during thattime. But there is another important ‘trickle-up’effect. From industry’s perspective, the lack of a pub-lic sector introduction strategy, in a world wheredonor-financed procurement will make or break the

1 While margins may vary across developing world vaccine prod-ucts, revenue opportunity as a whole is minimal. Vaccine rev-enues amount to only 1.5 per cent of global pharmaceuticalsales, and are roughly equivalent to annual sales of single block-buster drugs such as Lipitor or Prilosec. Of 2000 vaccine sales,low-income countries consumed nearly 50 per cent of doses(approximately 2.5 billion) but contributed only 3.3 per centof revenue (US$250 million).

2 In 2001, GAVI purchased 18 per cent per cent of the doses itawarded for combination vaccines; for monovalent HepatitisB, offtake in 2001 was only 11 per cent per cent of the award.For further details, see Mercer Management Consulting, 2002.

3 Average UNICEF procurement prices for Diptheris-tetanusand whole cell pertussis (DTPw) vaccine were well underUS$0.10 per dose throughout the 1990s. Since 1998, the priceof DTPw has actually been increasing – from US$0.06 perdose in 1998 to approximately US$0.09 in 2003. See GlobalAlliance for Vaccines and Immunization, 2001.

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market, means there is no credible information avail-able about the market in advance – no insight on mar-ket size, price or predictions about market maturity.In short, industry is left without the critical pieces ofinformation on which it usually bases production, com-mercialization and even earlier research allocation de-cisions.1 This makes the developing world an extremelyrisky market – one that may not offer sufficient rewardto justify the risks of engagement. The results of thisuncovered risk – as we have seen in the 10/90 gap andin the pipeline of products being developed2 – is thatthe developing world is relegated to receiving cast-offproducts from industrialized markets, or even worsethat industry is deterred from playing in developingcountry markets at all. And this, in turn, makes theproduct development goals of the PPPs much hardertoday.

Approaches to the solutionRecent effortsThe hepatitis B (HepB) experienceMerck introduced a plasma-derived hepatitis B vaccinein the developed world in 1981, at a price of aboutUS$30 per dose or nearly US$100 for the completeseries of three shots. The vaccine used a chemical puri-fication technology that resulted in a high-quality buthigh-cost product, specifically targeted to health work-ers and other high-risk individuals in industrializedcountries. “Only after the companies were successfulat producing such a Hepatitis B vaccine did they real-ize that the real need was not in the West but in thecountries of Asia and Africa” (Asian Development Bank,2001).

In 1986, several HepB experts formed the Interna-tional Task Force on Hepatitis Immunization with thegoal of creating supply and making the case for inte-

gration of a HepB vaccine in the developing world.The task force’s primary objectives were to lower theprice of the vaccine by transferring technology to lower-cost producers and to convince developing countriesand the international health community that HepBcontrol through immunization of infants should be atop priority.

The use of pilot projects in developing countrieswas central to the task force’s efforts, to prove that theproduct could be successfully integrated into immuni-zation programs with positive results. These demon-stration projects would prove to countries that HepBimmunization was both possible and worth doing andprove to industry that demand could exist at the rightprice, in the hope of creating incentives to supply atthat price.

In 1987, the task force designed and piloted its firstproject in Lombok, Indonesia. They solicited interna-tional tenders for supply of the vaccine; the tender re-quired that bidders offer Indonesia the same price onceit introduced the vaccine nationwide and offer the sameprice to other developing countries. The winner wasthe Korean Green Cross, which, capitalizing on ad-vances in lower-cost production technology, offeredto supply the vaccine at US$0.95 per dose, i.e. muchlower than the prevailing market rate of US$15–30per dose.

This low price fundamentally changed the nature ofthe HepB market. Through the late 1980s furtherdemonstration projects followed, and the task forceprovided assistance to several countries developing in-ternational tenders. By 1992 a number of Asian coun-tries, including China, Thailand, Indonesia, thePhilippines and Mongolia, had introduced HepB intotheir routine immunization programmes. The pricedropped as low as US$0.65 per dose in 1991.

In parallel, Merck and SmithKline Beecham intro-duced a recombinant DNA vaccine in the late 1990sat a price of about US$40 per dose. Competition withthe plasma-derived vaccine drove prices down, anddeveloping country manufacturers also began to sup-ply low-income markets at drastically lower prices.Prices dropped to just over US$1 per dose for therecombinant product by the early 1990s.

In 1992, WHO recommended that all countriesincorporate hepatitis B into their routine immuniza-tion schedules by 1997. Since then, price has contin-

1 While guaranteed information is obviously not available indeveloped world markets, biotechs and pharmaceutical com-panies are able to make market estimations based on assess-ments of need and willingness to pay. This market analysis is acritical part of ‘go/no-go’ decisions during the PD and pre-launch phases.

2 Less than 10 per cent of the amount spent worldwide on heathresearch and development is devoted to the major health prob-lems of 90 per cent of the world’s population. The impact ofthis has been clear in new drug development: of 1 233 drugslicensed worldwide between 1975 and 1997, only 13 were fortropical diseases (and only four of those were developed bycommercial pharmaceutical companies specifically for civilianhuman populations). See Institute of Medicine, 2003.



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ued to be a major barrier to the introduction of HepBvaccine in the developing world (even at US$0.30 perdose for the monovalent vaccine, it was three-to-fivetimes more expensive than older vaccines like DTP andmeasles1). Still, the availability of a low-cost supply haskept the price decreasing and the market reasonablyrobust; more recent support from GAVI and the Vac-cine Fund has accelerated introduction in many of theworld’s poorest countries. As of 2001, nearly 100 coun-tries provide the HepB vaccine as part of their routinecampaigns, but more than 60 per cent of the world’schildren2 – mainly the poorest of the poor – had stillnot received this potentially life-saving vaccine (Widdus,2000 and WHO, 2003).

From the time a hepatitis B vaccine was available onthe market, it took five years to begin a concerted glo-bal effort to bring the vaccine to the developing world;10 years to reach even double-digit coverage in South-East Asia; and 11 years to convince WHO to make auniversal recommendation for use. This lag in intro-duction and uptake is completely unacceptable whenit means five, 10 or 11 years of lives lost. The publicsector and the developing world were almost caughtby surprise with the availability of this effective butexpensive vaccine, and had to start from scratch in 1981by creating both supply and market demand. HepBcan be seen as a success story in some sense – pricesdid drop and the product was introduced with somesuccess – but it is a story that leaves room for improve-ment.

The haemophilus influenzae type b (Hib) experienceSince the late 1980s, highly effective vaccines againstHib have been licensed and widely used in the indus-trialized world.3 The effect has been dramatic – inci-dence of invasive Hib disease has fallen by more than90 per cent in those countries. Yet in the developingworld, Hib runs almost unchecked as very few coun-tries use these vaccines in routine immunizations. In2001, only 77 countries of WHO’s 191 member stateshad even introduced Hib vaccine, and most of this fig-ure represents introduction in North America, Europeand Latin America. The vast majority of countries inSouth-East Asia and Africa have still not introducedthe vaccine.

Cost is commonly cited as a significant barrier tothe introduction of Hib vaccine. Even at the price in

2000 of US$2 per dose for a three-dose schedule, Hibis significantly more expensive than traditional vaccines.In this sense, it is like the HepB vaccine. Perhaps moreimportant for Hib, however, is the fact that many gov-ernments are simply not convinced that the disease is aproblem in their country. Despite being a major causeof bacterial meningitis and pneumonia in young chil-dren worldwide, the Hib bacterium is difficult to iso-late without invasive procedures – all pneumonia, themost common result of the Hib bacteria, looks alikeso doctors and public health professionals rarely diag-nose or think about Hib.

By the mid-1990s international efforts to increasechildren’s access to Hib vaccines in the developingworld began in earnest. These efforts, led by a numberof scientific and public health champions, centred onestablishing and communicating the burden of Hibdisease. In the Gambia, West Africa, between 1993 and1995, researchers assessed the impact of a Hib conju-gate vaccine on the incidence of pneumonia overall ina double-blind trial involving over 40 000 infants, andconcluded that one in five episodes of severe child-hood pneumonia in the Gambia was Hib-related. Re-searchers in Chile have performed similar studies withvery similar results. As a result, a handful of countriesoutside the established industrialized economies pio-neered the introduction of Hib vaccine – mostly inLatin America and some in Africa.

In 1998 WHO published a position paper recom-mending use of Hib conjugate vaccines in routineinfant immunization programmes. Two years later, aHib vaccine trial similar to those in Latin America andAfrica was undertaken in Lombok, Indonesia with the

1 See footnote 2, page 163 or Global Alliance for Vaccines andImmunization, 2001 for details.

2 Global reported coverage in 2002 was 44 per cent (WHO-UNICEF estimate: 32 per cent). In WHO’s Africa region, 25per cent (6 per cent); Americas 74 per cent (58 per cent); South-East Asia 12 per cent (9 per cent). WHO, 2003.

3 Until the late 1980s, the only available Hib vaccines were basedon the polysaccharide, or sugary, capsule of the bacterium.These vaccines were protective in older children and adults,but not in infants – those at greatest risk of infection – becausetheir immune systems could not respond. The new generationof conjugate vaccines contain two components: the Hibpolysaccharide capsule and, attached to it, a carrier proteinantigen such as tetanus toxoid which stimulates a strong T-cellrelated immune response from the infant immune system. Sev-eral Hib conjugate vaccines have been licensed, including com-binations with DTP and DTP plus hepatitis B. For furtherdetails see P. Brown, forthcoming.

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aim of increasing awareness and uptake in Asia. Up-take today remains low – the WHO estimates 9 percent (12 per cent reported) in the South-East Asiaregion in 2002 (WHO, 2003).

In fact, based on the growing data on burden ofdisease and the still disappointingly low rates of up-take, GAVI has set itself a target of introducing theHib vaccine to 50 per cent of high-burden, low-in-come countries by 2005. If they achieve this target,they will still reach only half of the people who needthis vaccine most, more than 25 years after it was madeavailable.

Current effortsPreparing for a vaccine against meningitis AAfrica, in particular the ‘meningitis belt’ that stretchesfrom the Gambia and Senegal in the west to Ethiopiaand Somalia in the east, needs an effective vaccineagainst meningitis. The majority of meningitis cases inAfrica are caused by the serogroup meningococcal A.The technology required to make a suitable vaccine isknown, but no product has yet been developed.1 Infact, vaccine manufacturers had begun to work on avaccine in the 1990s, but discontinued these projectsby the end of that decade. The low level of researchand development in this vaccine has been attributed to“doubts about the ability to deliver the vaccine in someof the poorest countries with weak immunization in-frastructure, the future prioritization of introducingmeningococcal vaccines versus other disease efforts, andthe future willingness to actually purchase a vaccine ata ‘reasonable’ price” (Batson et al, 2003).

The Meningitis Vaccine Project (MVP) was createdby WHO and the Program for Appropriate Technol-ogy in Health (PATH) in 2001, with a US$70 milliongrant from the Bill & Melinda Gates Foundation, toaccelerate the development of a group A meningococ-cal conjugate vaccine and ensure it is “widely used in1- to 29-year olds to control [the] disease”. The vac-cine is also intended for use “as an EPI antigen inchildren under one year of age” (LaForce, 2003).Affordability is a core principle of the project, and MVPhas committed to delivering a vaccine priced at “wellunder $1 per dose” (LaForce, 2003).

MVP defines four strategic areas of focus: vaccinedevelopment; research and surveillance; vaccine roll-out and distribution; and communications, advocacy

and resource mobilization. It sees all four areas as “criti-cally interlinked not sequential”,2 and as such has en-gaged in a unique demand creation and signallingmechanism to stimulate vaccine production and supply.

Early in its life, MVP concluded that multinationalpharmaceutical companies would not be core suppli-ers of an affordable (< US$1 per dose) monovalent Aconjugate vaccine. Instead, they focused on transfer-ring conjugation technology from developed worldcollaborators to a developing world manufacturer thatcould scale-up, produce, lyophilize, pack, store anddistribute the vaccine. As part of this effort to engagea sustainable supplier, MVP is currently negotiatingan offtake agreement for the future vaccine in order tosecure long-term supply at low and predictable trans-fer prices.

Simultaneously, MVP is preparing the groundworkfor uptake by working with ministers of health and fi-nance in Africa to build awareness and demand, andworking with the donor community to secure finan-cial support.

The final results of MVP’s efforts remain to be seen,but progress is clear. Clinical lots of product are ex-pected to be ready this year and phase I trials will be-gin in sites across the ‘meningitis belt’ in early 2005.3

Accelerated Development and Introduction Plans forpneumococcal and rotavirus vaccinesThe Accelerated Development and Introduction Plans(ADIPs) currently in place for pneumococcal androtavirus vaccines represent another concerted efforton the part of donors to reduce the time lag betweenintroduction of products for industrialized and devel-oping nations, and to speed breadth of coverage in the

1 Polysaccharide vaccines were developed in response to epidem-ics of meningitis in industrialized countries in the 1960s. Thesevaccines are also used in developing countries but in responseto periodic epidemics rather than in routine immunization;their effect in Africa is limited, both by immunogenicity andmethod of use. Conjugate vaccines are in general more effec-tive, particularly in infants. In the 1990s, pharmaceutical com-panies were in the process of developing a conjugate A-Cvaccine, but instead focused solely on a meningococcal C prod-uct when the UK government issued a request to purchase in1999. A mening conjugate vaccine against serogroup C wasdeveloped for the UK soon after. For further details, seeLaForce 2003 and the Meningitis Vaccine Project website(www.meningvax.org).

2 From telephone interview with Marc LaForce, MVP.13 Ibid.



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developing world. The ADIPs are sponsored by GAVIwith an initial investment of US$30 million, and aremodelled after pre-launch teams that pave the way forthe introduction of new commercial products. Theyare meant to be three-year projects that alleviate someof the demand uncertainty faced by manufacturers, andprovide countries with the “information required tomake the best choice about introduction”.1

The ADIPs for both pneumococcal and rotavirusvaccines focus on three main sets of activities: estab-lishing the value of the vaccine, communicating valueand delivering value. Again, these are parallel – notsequential – activities.

The objective of ‘establishing the value’ is that bur-den of disease should be established and that the ben-efit of the vaccine be well understood at the countrylevel. This requires disease burden studies, efficacy tri-als and other fact-gathering activities to prepare thecase. Establishing value will also require a first assess-ment of latent demand, and an initial price estimate.

‘Communicating value’ is a unique recognition thateducation is a critical part of making the right deci-sions. The goal of these activities is to craft a messagethat convinces decision-makers to prioritize introduc-tion of the vaccine where it is appropriate, e.g. throughadvocacy and demonstration trials, and commit to long-term use.

Finally, a reliable and sustainable supply of the vac-cine as well as continued prioritization by national au-thorities will be required to ‘deliver its value’. ADIPswill work to assure long-term supply and delivery withsustainable funding.

Both the pneumococcal and rotavirus ADIPs areseeking to identify ‘early adopter’ countries which willbe the first to introduce their respective vaccines. Theseadopters will become the priority focus in terms ofenhanced disease surveillance, demonstration projectsand eventual introduction. Success in these countrieswill then lead to introduction and success in ‘earlymajority’ and ‘late majority’ countries. This user seg-mentation reflects the varied need, capacity and will-ingness of countries to adopt new vaccine technologies,and adapts commercial approaches to market segmen-tation and phased introduction.

In parallel, the ADIPs are working with multina-

tional pharmaceutical companies – the suppliers clos-est to market for both pneumococcus and rotavirusvaccines for the developing world – to negotiate pric-ing arrangements. All of this is being done while prod-ucts are still in development so the ADIPS arepotentially shaping the products being created andexplicitly trying to influence future supply dynamics.

Ensuring access to AIDS vaccinesThe International AIDS Vaccine Alliance (IAVI) hasalready begun to consider the issues around access toAIDS vaccines for the poor, though the developmentof these vaccines is still in its early stages. A study com-missioned by IAVI in 2000 (Widdus, 2000) recom-mended five essential steps to ensuring simultaneousworldwide access to AIDS vaccines as soon as they wereready for market:

1. Effective pricing and global financing mechanismsdeveloped in advance, to ensure products could bepromptly available for use where they are needed.

2. Mechanisms need to be developed to make reliableestimates of demand for specific vaccines and toensure creation of production capacity to permit ac-celerated worldwide access.

3. Appropriate delivery systems, policies and proce-dures need to be developed for adolescents, sexu-ally active adults and other at-risk populations.

4. National regulations and international guidelinesgoverning vaccine approval and use must be har-monized.

5. Immediate efforts should be undertaken to achievemaximum use in developing countries of one ormore currently underutilized non-AIDS vaccines inorder to demonstrate global commitment to effec-tive worldwide deployment of important vaccines.

A second study (Madrid, 2001) focused on specificactions that governments could take to facilitate theabove goals, including support for regulatory reformand tiered pricing. This is an important reminder thatPPPs may be the lead champions of these efforts, butsuccess will require others to act as well.

In addition to further work to detail the above rec-ommendations, two complementary need and demandestimation exercises are already well under way: a jointIAVI-WHO-UNAIDS project and a European Com-mission-funded World Bank project.1 From telephone interview with Orin Levine.

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This integrated approach for an early-stage vaccinereflects a new and important shift in thinking abouthow best to prepare for the introduction and use of anew product in the developing world. In this forwardthinking, the international community may have anunprecedented opportunity to influence the vaccinebeing developed, so that it is useful for (and compat-ible with) conditions in the developing world.

Guaranteeing a market through advance contractingOne way the donor community could enhance themarket for new global health vaccines is by fundingmulti-year advance guarantee agreements. These com-mitments take the form of specific legal contracts toencourage the production of existing vaccines or thedevelopment of new vaccines, e.g. near-term vaccineslike rotavirus and pneumococcus, or early-stagevaccines for HIV, TB and malaria. In either scenario,these contracts would be closely associated with esti-mated demand from developing countries and providefor some sort of price guarantee as a means of offset-ting some of the risks facing vaccine manufacturers. Inaddition, these contracts may need to allow for ‘dy-namic pricing’, i.e., allowing for higher prices when aproduct is first introduced (when quantities tend to belower) and then reduced prices over time as volumesincrease and, eventually, as developing countries as-sume the responsibility for payment. Liability and theoverall credibility of the offer are two important issuesthat must be addressed for this mechanism to haveimpact.

The Pull Mechanisms Working Group – funded bythe Bill & Melinda Gates Foundation and convenedby the Global Health Policy Research Network at theCenter for Global Development – has spent the pastyear evaluating the feasibility and potential impact ofthese tools in the PD portfolio, and has delivered pre-liminary conclusions that confirm both their practical-ity and importance.1

Emerging lessonsIn order to meet their public health objectives in aparticular disease area, PPPs must be concerned withmitigating both upstream and downstream risks in the

vaccine market. Direct push funding will facilitateresearch and product development by directly reduc-ing cost and therefore risk. But laying the groundworkfor product introduction and sustained use – by creat-ing predictable demand and securing financing – isessential to affecting both the timing and the speed ofuptake, and the nature of supply itself.

Concern with the market requires more than thetraditional approach of having sympathetic experts inWashington or Geneva understand the global burdenof disease. Concern with the market requires demandcreation in the developing world – by communicatingthe value of the vaccine to its users and understandingdemand constraints like willingness and ability to pay.It requires demand signalling to reduce unpredictabilityfor industry – by demonstrating willingness to purchase,guaranteeing willingness to pay or even generating acredible demand estimate. And it requires fund-raisingand financial planning to support the market. New re-sources offered through institutions like GAVI and theVaccine Fund create a unique opportunity to improveon a poor track record of vaccine introduction. Thelessons of HepB and Hib have led to new approachesbeing implemented today. The results of these newinitiatives have yet to be proven, but progress is prom-ising. At a minimum the vaccine community appearsto be converging around some critical success factorsfor new product introduction.

Start earlyPlanning for introduction when a product is on themarket is already too late. Past experiences with hepa-titis B and Hib demonstrate the dangers of such anapproach: products were not produced in a profile orat a price that would serve the needs of the developingworld; it took years to generate the demand, financingand international support to affect change in the prod-uct profile; and the work continues even today – morethan 20 years after the introduction of the originalproduct– to reach the full life-saving potential of thesevaccines in the developing world. Preparing for uptakemust run in parallel with product development. Start-ing early to create the market, e.g. through burden ofdisease assessment and communications with countriesand with the donor community, is critical to accelerat-ing the impact of vaccines once introduced. Equallyimportant, however, is the opportunity to use demand

1 Report of the Pull Mechanisms Working Group forthcomingfrom the Center for Global Development. Contact Ruth Levine([email protected]) for details.



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as leverage to shape the products being developed to-day. This is, after all, how PD works in industrializedmarkets – insight into what a market wants to buy drivesinnovation and product development. Advance demandplanning gives the international community unprec-edented leverage to partner with industry early in thePD process to ensure the most practical and useful vac-cine is developed for those who need it most. This mayfundamentally affect the product (e.g., a vaccine thattargets African clades of HIV) or be a minor tweakthat significantly affects usage in the field (e.g. testinga product’s full thermostability instead of the standard2–8 degree range). Finally, thinking early about finan-cial sustainability and a long-term supplier landscapemay have an impact on push funding or intellectualproperty decisions today.

Take an integrated approachPreparing for uptake is more than just estimating needor even estimating demand, it is an integrated packageof measurement, education, understanding and per-suasion that must affect demand, supply and financ-ing. If sustained use of a new product is the end goal,then all three of these pieces must be addressed to-gether in an introduction strategy. Demand for mostproducts, including vaccines, is created; willingness touse can and often must be created through educationabout the burden of disease and communication aboutthe value of a vaccine; ability to use may require someparallel investment in health systems. Supply will clearlybe shaped by the nature and value of demand – com-mercial entities will respond to credible demand esti-mates (both for quantity and also for product profile)as they invest in research, development, clinical trials,capacity installation and licensure. The internationalcommunity must not only understand when and howit can affect these supply decisions, but also engage inan evidence-based dialogue with industry in order tolay the foundations for sustainable supply. Finally fi-nancing – the glue that will link supply and demand –must be in place in advance to leverage the power ofdemand today and ensure long-term supply into thefuture.

Commit to a long-term visionNeither product development nor introduction is a goalin itself. It is the long-term vision of reducing burden

of disease that motivates the key stakeholders, andtherefore should be the starting point for all interme-diate steps. PD and planning for introduction must beundertaken with a view to accelerating time to marketmaturity, and more importantly a particular vision ofhow that mature market will impact public health. Themature market will combine sustainable supply at af-fordable prices with sustainable use for all those coun-tries that need and want the product – and this visionwill have immediate impact in terms of target productprofiles, demand forecasts, prices paid in the initialyears, desired number of suppliers and the amount/structure of financing that must be in place today. Itis, however, a long-term vision with many moving partsand therefore must be approached on a realistic timehorizon. The phased introduction approach of theADIPs may offer some lessons on setting intermediategoals in an integrated long-term planning process, forexample, to get a product developed (years 0–5 forthe near-term candidates of the current ADIPs), tointroduce in early adopter countries (years 6–9), tospread broader coverage with multiple suppliers (years10–13), and finally to reach market maturity (years 13–15). These stages then have implications for financingneeds and priority PPP activities today.

Dedicate the capacity to do it rightPlanning for product introduction requires supple-menting existing public health and scientific expertisein PPPs with a particular skill set analogous to productlaunch teams in a pharmaceutical or biotechnologycompany. These teams may include scientists and port-folio managers, but should also include people withbusiness development, market planning and market-ing skills. The key activities required for successful up-take planning certainly include disease surveillance, butalso demand estimation, marketing and communica-tions, financial planning and knowledge of commer-cial product development practices. This is not apart-time job; it requires dedicated capacity to do itcorrectly and probably requires funding upfront to bemost efficient. These skills are available for hire butshould also be internalized in the international com-munity so public sector ‘product launch teams’ can beassembled as needed.

If we get this right, there will be increasing num-bers of products for which this type of upfront plan-

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ning is critical to achieving meaningful health impact.This is a virtuous cycle that needs to begin today.

SourcesIn addition to the references cited below, this docu-ment was prepared following telephone interviews ande-mail exchanges with: Amie Batson, Senior HealthSpecialist, The World Bank; Alan Brooks, Senior Pro-gram Officer, Bill & Melinda Gates Children’s Vac-cine Program at PATH; Paul Fife, Health Advisor atthe Center for Health and Social Development, Nor-way; Marc LaForce, Director of the MVP; Orin Levine,Director of GAVI’s Pneumococcal ADIP; and RuthLevine, Director of the Global Health Policy ResearchNetwork, Center for Global Development.

Immunization Financing in Developing Countries andthe International Vaccine Market: Trends and Issues.Manila, Philippines: Asian Development Bank. 2001.

Batson A, Glass S, Seiguer E. Economics of Vaccines:From Vaccine Candidate to Commercialized Project.In Bloom B, Lambert PH (eds), The Vaccine Book.San Diego, CA: Elsevier Press, 2003.

Brown P. Hib Vaccination in Chile and The Gambia.What’s Worked: Accounting for Success in GlobalHealth. Washington, DC: Center for Global Devel-opment, Global Health Policy Research Network,What’s Worked Working Group, forthcoming.

Brown, P. The Invisible Culprit. GAVI ImmunizationFocus – Special Feature. Geneva: GAVI, 2000.

Centers for Disease Control and Prevention. 2003.Global Progress Toward Universal Childhood Hepa-titis B Vaccination, 2003. Morbidity and MortalityWeekly Report, 2003, 52(36).

Center for Global Development. Hib Immunization:Success in Contrasting Countries. What’s Worked?Success Stories in Global Health. Washington DC: IIEPress, forthcoming.

GAVI Financing Task Force. Out of the Box. Back-ground reading prepared for the Out of the Boxmeeting, Warrenton, VA, USA, 25–26 July 2001.

Institute of Medicine. Financing Vaccines in the 21stCentury: Assuring Access and Availability. Reportof the Committee on the Evaluation of VaccinePurchase Financing in the United States. Washing-ton, DC: The National Academies Press, 2003.

LaForce FM. Defeating the Scourge of MeningococcalDisease in Africa: A Work in Progress. 2003. Avail-able at www.meningvax.org

McKinsey & Company. Accelerated Introduction ofPriority New Vaccines in Developing Countries –From Credible Investment Case to ADIP. Report pre-pared the Global Alliance for Vaccines and Immu-nization, 2002. Available at www.vaccinealliance.org.

Madrid Y. A New Access Paradigm: Public Sector Ac-tions to Assure Swift, Global Access to AIDS Vaccines.IAVI Access Project White Paper. New York: IAVI,2001.

Mercer Management Consulting. Lessons Learned: NewProcurement Strategies for Vaccines. Final Reportto the GAVI Board, 2002. Available at www.globalalliance.org.

Widdus R. AIDS Vaccines for the World: Preparing Nowto Assure Access. Prepared for IAVI. An New York:IAVI Blueprint, 2000.

Wittet S. Hepatitis B Vaccine Introduction: LessonsLearned in Adovcacy, Communication and Train-ing. Bill and Melinda Gates Children’s Vaccine Pro-gram at PATH Occasional Paper #4, 2001. Availableat www.path.org

Progress Towards Global Immunization Goals – 2001.Summary presentation of key indicators. WHO,2003. Available at www.who.int/vaccines


ANNEX 9J

The costs of developing vaccines:Case study of VaxGen’s HIV candidate vaccine

Donald P. Francis (Brisbane, CA, USA)

The cost of developing any new pharmaceutical prod-uct is high. A recent study from Tufts University (USA)estimated the cost required to develop a single drug tobe US$802 million.1 Although some have debated theexact number, no one will debate that it costs severalhundred million dollars for each product brought tomarket. This is true for therapeutic drugs as well aspreventive vaccines.

Despite the large costs, pharmaceutical companiescontinue to invest in drug development for the poten-tial benefits (profits) received from successful products.For example, products like atorvastatin (Lipitor) andomeprazole (Prilosec) each bring in revenue of approxi-mately US$6 billion per year. Evidently, society valuesthese drugs that, respectively, lower cholesterol anddecrease heartburn. These high-profit drugs are the‘blockbuster’ products that all pharmaceutical compa-nies seek.

Vaccines, unfortunately, do not fit into this ‘block-buster’ category. The atorvastatin/omeprazole rev-enues far outstrip revenues from any vaccine. Indeed,the annual revenue for one of these drugs is equivalentto all vaccines combined! Moreover, the modest rev-enue from currently marketed vaccines comes prima-rily from selling products in industrialized countries.The minimal revenues from sales in the developingworld hardly register on the same scale (see Figure 1).Thus, the financial incentive for pharmaceutical com-panies to develop vaccines for the developing world –extremely important products by anyone’s assessment– is minimal.

In the field of AIDS, and as is the case for otherinfectious diseases, therapeutic drug candidates andvaccine candidates compete for the same developmentresources. Looking back, most would have anticipatedthat an HIV vaccine would have successfully completed

Executive summary

In recent years, great progress has been made towardsboth the understanding of infectious diseases and the

means by which to make vaccines to prevent them.However, the powerful tools that have been developedto make vaccines can be used just as effectively to makeother pharmaceutical products. Thus, there is compe-tition for their use. Unfortunately, market forces, drivenby social values and financial resources of the industri-alized countries, direct these tools away from the de-velopment of important vaccines for developingcountries towards that of high-profit therapeutic drugsfor wealthier parts of the world. As a result, few ur-gently needed vaccines are being developed. Unlessnew models are constructed which alter this paradigm,the full power of modern science will not be harnessedto prevent disease in the less developed parts of theworld.

Here, the example of the development of a candi-date HIV vaccine is presented. This vaccine, know asAIDSVAX, required over 20 years of development timecosting approximately US$200 million. AIDSVAX wasevaluated in very high-quality studies in Thailand, dem-onstrating that world-class vaccine trials can be suc-cessfully completed in many areas of the world. Withminimal efficacy measured in the phase III studies,development of this vaccine is far from complete.

In the end, the problem is not the lack of either thescientific/technical tools to make vaccines or our abil-ity to conduct complex clinical vaccine trials in regionswhere tropical diseases exist. The problem rests withthe will and commitment to finance the developmentof these important public health tools.

1 Frank RG, J. Health Economics 2003; 22:325–330.


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the development process far earlier than an HIV anti-viral agent. At the time of the discovery of HIV, therewere far more viral vaccines available than there wereantiviral therapeutic drugs. But the opposite happened.Despite the immense challenge of developing antiviraldrugs, more than a dozen are currently available foruse whereas there is still no vaccine. I do not believethis reflects a contrast in the scientific difficulty to de-velop a vaccine versus a therapeutic. Instead, I believeit is the imbalance of market forces that has driven in-dustry towards antiviral agents where the profits arefar greater.

No one would debate that the social need forvaccines is enormous. But this immense need is notmet with the financial resources to drive developmentof these products. Thus, although the social need isthere, it does not translate into a social valuation highenough to drive industry to produce. Such ‘marketfailures’ of vaccines have received extensive discussionsin the literature, including some dealing specifically withAIDS vaccines.1

With such an imbalance, it should come as no sur-

prise that many large pharmaceutical companies haveabandoned the vaccine business (see Figure 2). As aresult, the number of vaccines being developed is smallcompared to the number of therapeutic products inthe development pipeline. This is despite the monu-mental advances that have been made in microbial ge-netics, immunologic methods, recombinant DNAtechnology and manufacturing. With these new tools,the ability to make safe, effective and economicalvaccines has vastly increased in recent years. Yet, thenumber of products in the pipeline does not approachthe potential that modern science offers.

One is tempted here to say that such a situation isthe fault of the pharmaceutical industry. It is not. So-ciety, in its wisdom, decides, directly or indirectly, whatproducts it wants (values) and industry attempts to fillthe resulting void. If society valued vaccines (i.e. wouldpay for them), industry would develop them to meetthat value. Putting yourself in the position of a boardmember of a pharmaceutical company makes it easy tosee why decisions are made not to develop vaccines.Board members have the legal responsibility to makedecisions that maximize the financial return for theirinvestors. If the choice before you, the board member,is to invest corporate resources into developing a po-tential blockbuster drug or a vaccine, the decision youwill make is obvious – go for the blockbuster. Unlessequivalent profits can be expected from vaccines, theywill not be developed by industry. If each new drug orvaccine consumes the same development costs, whywould you choose to invest in the low-yield vaccinesover the high-yield therapeutic drugs?

All must recognize that the expertise to developvaccines rests primarily within the pharmaceutical in-dustry. Basic research often comes from university orgovernment laboratories, but moving such discoveryfrom the bench to a final vaccine product requires theexpertise that rests in industry. If industry continuesto abandon the vaccine field, fewer and fewer vaccineswill be developed. Unless a new model is constructedwhere publicly supported institutes/projects, havingindustrial expertise, are funded to develop vaccines(‘push’), or major funds are established to purchasevaccines (‘pull’), little change will be forthcoming. This

6

4

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0

$ bi

llion

s Allvaccines

Lipitor PrilosecVaccines –less developed

countries

Figure 1. Annual revenue from ‘blockbuster’ drugsvs. vaccines

30

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10

5

0

Num

ber o

f pha

rmac

eutic

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Figure 2. Large pharmaceutical companies developing andmarketing vaccines, 1967–2004

1 Batson A, Ainsworth M. Private investment in AIDS vaccinedevelopment: obstacles and solutions. WHO Bulletin, 2001,79:721–726.

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unfortunate situation is true for the industrialized partsof the world where limited potential profit keeps somevaccine development alive. For the less developed partsof the world, it is nearly hopeless with the currentmodel.

Perhaps we can gain some insight into what is re-quired to develop a vaccine by examining the AIDSVAXstory.1 It will also help the reader to better understandthe considerable effort required to bring these prod-ucts from the bench to the public. What is importantin this review is to understand that the effort requiredto develop AIDSVAX is similar to the effort requiredto develop any pharmaceutical product. Thus, from acompany’s standpoint, a decision-maker must decideif the company is going to expend this effort on thedevelopment of a vaccine that has a questionable po-tential market or on a therapeutic drug whose poten-tial market is much greater.

For HIV/AIDS, there is an obvious social need.The medical and social costs for AIDS have been sub-stantial for almost all countries of the world. For sub-Saharan Africa, with upwards of 30% of the adultpopulations infected with this nearly 100% fatal virus,the adverse impact is stunning. Here the demand for avaccine should be obvious. Indeed, from a social van-tage point, the several hundred million dollar devel-opment costs for a vaccine are small compared to thetens of billion dollars in direct medical costs that HIV/AIDS accumulates each year.2 One would think, giventhis immense economic, public health and personalthreat, that dozens of HIV vaccines would have com-pleted phase III by now and at least several would belicensed. But none has been. Unfortunately, the worldis not always logical.

For VaxGen’s vaccine, a total of 20 years has beenconsumed to date and development is far from com-plete. Genentech started the project in 1984 andstopped after the 1994 decision by the United States’National Institutes of Health (NIH) not to fund thephase III trial. VaxGen was then established to com-plete the development and, after receiving private fund-ing, restarted the programme in 1997. Two candidate

vaccines were developed – one matched to HIVsubtypes found in North America and Europe and theother matched viruses found in South-East Asia. Thephase I/I studies in the United States and Thailandwere conducted between 1997 and 1999. The phaseIII studies, one in North America and Europe and onein Thailand, were completed in 2002 and 2003 (seeFigure 3). Unfortunately, the vaccines’ efficacy meas-ured in these trials was low and much additionaldevelopment will be required.

The expense for such an endeavour can be meas-ured from at least two points of reference. One is di-rect financial cost. It is estimated that Genentech spentUS$50 million in the early stages of development. Inaddition, VaxGen spent approximately US$130 mil-lion, the US government contributed another US$11million (plus in-kind efforts by CDC in Thailand) and,in the final months of the Thai trial, the Bill andMelinda Gates Foundation contributed US$2 million(Table 1). Thus, in total, the vaccine development,manufacturing and clinical trials, including two largephase III trials, cost almost US$200 million.

Besides being time consuming and expensive, vac-cine-development programsmes, like the one forAIDSVAX, are complex and require multiple, highlytrained teams with skills ranging from laboratory test-ing and manufacture to clinical research and regula-tory affairs. VaxGen employed over 100 people toconduct these trials. An additional 800 people wereemployed outside of VaxGen in four countries and 78clinical sites. Over 12 000 volunteers were screened toidentify the 7 930 volunteers for the two studies. Thesevolunteers had over 135 000 clinic visits, 55 000 in-

1 Francis DP, Heyward WL, Popovic V, et al. Candidate HIV/AIDS vaccines: lessons learned from the world’s first phase IIIefficacy trials. AIDS 2003, 17:147–156.

2 Mann J, Tarantola D (eds) AIDS in the World II. Oxford:Oxford University Press, 1996.

Table 1. Approximate costs of AIDSVAX’s development,1984–2004

US$ million

Genentech* 50

VaxGen* 130

US government + 11

Bill & Melinda Gates Foundation 2

Total 193

* Private investment+ CDC and NIH(Does not include US$100 million for manufacturing facility in Republic of Korea.)

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jections and 71 000 blood draws, and submitted over1 million case-report forms. Each blood specimen hadto be processed, stored and tested. Each case-reportform had to be entered into a database. In the end, allof the data had to be analysed.

Important for this discussion was the success of theThai investigators in conducting the world’s first large,phase III trial of a candidate AIDS vaccine in the de-veloping world. As mentioned above, such trials, espe-cially given the Good Clinical Practice standardsrequired by international regulatory authorities, arecomplex. Yet, investigators, regulatory and ethical over-sight committees, and clinics dealing with volunteersplanned and conducted the Thai trial to the higheststandards. Thus, the experience in Thailand added fur-ther evidence supporting the feasibility of conductingchallenging vaccine trials in less developed areas of theworld.

Interestingly, the costs for the development and tri-als were not much different for the Thai or NorthAmerican/European vaccine. The laboratory develop-ment costs and manufacturing for the two vaccines wereidentical. For the clinical trials, the most expensive partof vaccine development, the costs per –volunteer, wereonly slightly less in Thailand than in the United States,Canada and the Netherlands. The Thai trial enrolled2 527 volunteers and the North American/European

Figure 3. Development timeline for candidate HIV vaccine, AIDSVAXAIDSVAX B/B for North America and Europe; AIDSVAX B/E for East Asia (Thailand)

84 85 86 87 88 89 90 91 92 93 97 98 99 00 01 02 03

AIDSVAX research begins

Nucleotide sequenceof HIV determined

Antibodies to rgp 120neutralize HIV

Antibodiesinhibit bindingto CD4

IIIB producedChimps protected (IIIB)

IIIB Phase I

MN produced

MN Phase I

MNPhase II

Chimps protected (MN)

B/B and B/E produced

B/B Phase I/II

B/E Phase I/II

B/B Phase III Trial

B/E Phase III Trial

Genetech, Inc VaxGen, Inc

trial enrolled 5 403 volunteers. Paralleling the numberof volunteers in each trial, the actual costs for the Thaitrial were about half of the larger, North American/European counterpart.

A second point of reference involves the opportu-nity costs. The money and person years expended todo this effort are large and, if not invested in HIV/AIDS vaccines, could have been invested in somethingelse with, perhaps, more chance of success. US$ 200million is a considerable amount of cash. But cash canbe replaced. Time cannot. Twenty years forms a sub-stantial portion of a company’s history and the careersof its staff.

In summary, there exists a huge potential healthbenefit offered by the recent immense advancementsin modern science and vaccinology. Although small inrelation to the costs of the targeted disease, the costsof moving bench-science advancements to new vaccinesare considerable. Currently, no well developed systemexists that either pushes or pulls vaccine developers todevelop new vaccines against diseases that are preva-lent in the less developed parts of the world.

In the end, it is social value. If society values vaccinesfor diseases like AIDS, and if that value is translatedinto well coordinated efforts to develop them, theywill be developed. Viewed objectively, the problem issimple. It is us.

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ANNEX 9K

Requirements for vaccine product and field sitedevelopment at a licensure standard

Jerald C. Sadoff (Aeras Global TB Vaccine Foundation, USA)

and risk is the critical part of the overall plan. The abil-ity to convince talented local investigators to take own-ership of the project and dedicate themselves to itsdesign and execution will ultimately, however, deter-mine its success.

Field site developmentThe best way to develop a field site is to actually per-form a vaccine trial. This will provide the real basis forunderstanding the political, legal, infrastructural, lo-gistic, communication, scientific and professional de-velopment and other requirements unique to theparticular site. Obviously the best way to carry out asuccessful vaccine trial is to perform it in a site andwith investigators where a successful vaccine licensingtrial has recently been performed. If this is not possi-ble, then in the two or three years of ramp up, phase Iand II studies should be conducted at the field siteand an epidemiological cohort study performed. Thisstudy should be designed with enrolment entry, in-formed consent, case report forms, case detection andfollow-up, monitoring and data management systemssimilar to those to be used in the trial. The study willserve two functions: a logistic and professional devel-opment function and a scientific estimate of diseaseincidence and volunteer drop-out rates.

Certain fundamental things have to occur in orderfor a phase III vaccine study to lead successfully to thegranting of a licence:

• First and foremost, the disease the vaccine is de-signed to protect against must occur in the immu-nized population at a rate consistent with predictionsthat the study sample sizes were based on. For thisto occur, a well defined case definition is requiredat the time of epidemiological estimates as well asthe curve of change of incidence of disease over time.

Executive summary

Field site preparation, clinical testing, process devel-opment, manufacturing and licensing of a new vac-

cine in the developing world will cost at least US$150million depending on the product and market require-ments. Total costs for preparing two sites for phase IIIclinical trials providing the necessary infrastructure, epi-demiology and phase I and II trials will be aroundUS$14 million. Phase III clinical trials in 10 000 sub-jects carried out in these two sites including productcost will be around US$26.5 million. The processdevelopment will be US$12–15 million. A total ofapproximately US$55 million will be required to doeverything necessary for a 10 000-subject efficacy trialrunning at licence standard. A US$100 million esti-mate for factory construction is on the low side anddependent on yield and market requirements.

An overall planField sites and vaccine process and analytic develop-ment should be designed with the view to supportingthe licence-granting procedure so that the vaccine canbe used by millions of individuals in the developingworld. This field site and vaccine product development(PD) is therefore part of a PD plan with milestonesand ‘go/no-go’ decisions. In its initial iteration, thisplan contains the pipeline of lead, back-up and second-generation products, a rudimentary product profile forthese vaccines, product and assay developmenttimelines and an early clinical development plan forthe lead candidates. Eventually this plan becomes highlydetailed and goes all the way through to full-scalemanufacturing. This is a time- and resource-driven planthat incorporates known risks to shorten as much aspossible the time taken to launch and make availablethe new vaccine. This balance between time, resources


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• Volunteer retention rates must be high because thoselost to follow-up may be considered as vaccine fail-ures in the intent-to-treat analysis, and thus elimi-nate the potential to demonstrate the vaccine’sefficacy.

• Follow-up of all adverse events, especially seriousadverse events and death, has to be very stringent.Verbal autopsies will not suffice; if that is all thatcan be obtained in the area the site may not be suit-able for efficacy trials.

• Informed consent must be given properly. This re-quires considerable training of the personnel ob-taining consent.

• Vaccine must be properly transported to and storedat the site, and administered.

• Blood samples must be properly drawn, processed,handled, transported and stored. Assays whose op-erational characteristics have been validated to anindustry and regulatory standard must be used.

• Detection of disease must have an active surveillancecomponent that is comprehensive and cannot relyentirely on a passive surveillance system. The sam-ple size estimate and the disease incidence estimatesmust have taken into account the effect of this ac-tive surveillance and treatment. This requires assem-bly and training of active surveillance teams.

• The entire process of consent, immunization,adverse event follow-up, blood draws, follow-upvisits, disease detection and all other aspects of pro-tocol execution must be rigorously monitored at thesite level and at the data safety and monitoring board(DSMB) level. Such monitors require training if notavailable and a rapid communication system betweenthe field site and DSMB needs to be operational.

• All of the data collected in the study need to be putinto a database. Reliable transport of the data to acommon database is required. The data need to bechecked for accuracy, consistency and completenessbefore the database can be locked prior to un-blind-ing. This has sometimes taken more than two yearswhich is unacceptable. Current industry standardsare 30 to 90 days.

A longitudinal cohort study utilizing the entry crite-ria, case definitions, consent forms, case report forms,active and passive surveillance systems, monitoring anddata management systems, blood collection, process-

ing and transport and assays envisioned for the phaseIII trial is the ideal way to ensure the professional de-velopment, logistical support, communications andinfrastructure will be in place to support a well de-signed trial. Such a trial will also prepare communityleaders as well as officials throughout the system forthe phase III trial.

At the same time that the large longitudinal cohortstudy is under way, phase I and II vaccine trials in thepopulation at the field site should also be undertaken.The local scientific community should be encouragedto become involved in the trials, so that they can ben-efit from early scientific papers on the vaccine. Thesetrials will determine realistic time frames for ethical andregulatory review in the site and country. They willalso flush out political and other problems that may befaced in the phase III trial.

A training programme to encourage professionaldevelopment of those involved in implementing thetrial is critical for success. The programme should in-clude academic and practical aspects of GCP and otheroperational aspects of the trial and needs to be imple-mented early in the field site development plan.

The success of the phase I, II and III trials is totallydependent on identifying talented and dedicated localinvestigators who are integral to the design of all stud-ies and their implementation. If it is a multi-centre trial,a local lead investigator should be in charge of the trialin the region and play a large role in the overall planning.

For generic costs, it takes about three years to de-velop capacity to do large clinical trials and that thetotal cost is approximately US $3.9 million, excludingthe cost of phase I and II trials and the data manage-ment system. The costs would be more in the first yearand less as time went on, but annual average costs arepresented in Table 1.

Table 1

US$

General infrastructure 100 000Cohort studies 700 000Laboratory capacity 300 000Professional development 200 000

Total per year 1 300 000Total (3 years) 3 900 000

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This provides a community ready to enrol 4 000 to5 000 people per year in a manner fully compliant withhighest GCP standards. The cohort studies include aneonatal cohort and an adolescent cohort. The epide-miological parameters studied would be limited to base-line prevalence of infection and disease and annual riskof infection and disease and the requirements for co-hort retention and formation would also be known.The laboratory capacity includes diagnostic labs andinfrastructure to obtain, pre-process and transportimmunology specimens.

The phase I studies cost around US$7 500/subjectand the phase II around US$2 500/subject includingmonitoring. Data management would be aroundUS$1 200/subject at this stage. For phase III study,costs are around US$1 500/subject plus US$1 000/subject for monitoring and data management. Labo-ratory costs of approximately US$1 million should beanticipated. Product costs of at least US$500 000would be for consistency lots. Table 2 lists estimatedcosts for clinical phase I , II and III studies.

Table 2

US$

Phase I (for 50 subjects): 435 000Phase II (for 600 subjects): 2 220 000Development of a validated assay: 500 000Capacity Building (see Table 1) 3,900,000Total cost over 3 years: 7 055 000Phase III (10 000 subjects):

Study costs: 15 000 000Monitoring and data management: 10 000 000Laboratory: 1 000 000Product costs: 500 000

Total (for 10 000 subjects): 26 500 000

It is important to include the costs of phases I and IIinto the field trial development costs because a sitecannot really be developed without performing thesestudies at the site. If more than one site is being con-templated, then the phase II studies can be dividedbetween the sites.

Product developmentDevelopment of the processes for vaccine productionand analytic tools for release and stability at licencestandard should happen while field site developmentis occurring. Phase III trials should not begin withvaccines that are made by processes considerably dif-ferent from those envisioned for full-scale manufac-turing. Otherwise, despite the potential for bridgingstudies, the efficacy trials may need to be repeated.There is considerable controversy here, but it is gener-ally accepted that a phase III efficacy trial should beperformed with the final factory product or at leastwith a process that with some modifications can be-come a full-scale process.

The fundamental requirements that should be de-veloped in order to make decisions concerning whento build and how to size factories are listed below. Thesecritical decisions on when and how much capital toinvest determines the timing of availability of vaccine.Lack of availability of certain vaccines for the develop-ing world despite proven clinical efficacy has been amajor tragedy in the past and continues today. Thebetter the quality of the information about each of thefive areas listed in Table 3, the sooner a vaccine can bemade available and the more likely that investment willoccur and will not be wasted.

Product profile characteristics of importance tomanufacturing listed above, tied to product profilecharacteristics related to clinical performance of thevaccine such as efficacy, adverse event profile, deliverymechanism (i.e. needle, nose, oral) and costs, all affectestimates on the amount of vaccine needed for eachterritory as well as estimates on time to regulatory ap-proval. These estimates, which justify the amount andtiming of capital investment for factory construction,are therefore critical factors for success of public pri-vate partnerships attempting to save as many lives aspossible.

Of course all costs are product related. Estimatesderived from live viral vaccines and recombinant pro-tein vaccines expressed in E. coli are listed in Table 4.

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Table 3

1) A product profile in terms of:a. technical specifications for release of the productb. dosagec. regimend. method of deliverye. target populationf. final packageg. multiple and single dose requirementsh. Stability, storage and transport issues:

i. minimum acceptable expiry period after shipping fromfactory

ii. estimate of bulk and finished product storage require-ments

iii. Manufacturing window filling model which incorporates1. maximum potency at release in terms of clinical safety2. minimum potency at expiry in terms of clinical

efficacyiv. Bulk stability datav. Final product stability datavi. Stability data during and following reconstitution out of

storagevii. Stability data in relation to temperature and transport

i. Estimates of costs of vaccine bulk, final product and packagedproduct.

2) A fully developed, reproducible and scaleable vaccine manufactur-ing process for transfer to a full scale manufacturing facility has been developed where:a. Estimates of yield at scale initially and after improvements are

reasonably accurateb. Losses during downstream processing and lyophilization have

been determined to satisfy overall yield estimatesc. Processes are robust enough to reduce failure rates to an

acceptable and predictable leveld. Initial materials are readily available from reliable suppliers

ideally with multiple sources3) Fully developed, validated and statistically characterized release and

stability assays which demonstrate:a. potency, based on well characterized and properly stored and

characterized standardsb. product purityc. freedom from adventitious agents

4) Roll-out of regulatory approvals in each territory including packag0ing, pricing and other required governmental approvals.

5) Roll-out of estimated product requirements by quarter and terri-tory following regulatory approval and other governmentalapprovals.

Table 4. Material for Phase II and potentially for Phase III

US$

Process development 2–5 millionVaccine 1 million

Final factory scaleProcess development 12–15 millionFactory design and construction 70–500 million3 vaccine consistency lots 100 000–1 500 000(can possibly be sold)

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ANNEX 9L

Product development public-private partnershipsfor diseases of poverty

Are there more efficient alternatives? Are there limitations?Robert G. Ridley (Director, UNICEF/UNDP/World Bank/WHO Special Programme for

Research and Training in Tropical Diseases)

level of a small pharmaceutical company, but there is alikely to be a doubling of size in the coming five yearsresulting in many more individuals being engaged inproduct R&D for diseases of poverty. There are sev-eral areas that warrant future discussion, support andoversight to ensure:

• The partnerships are neither over-competitive witheach other, nor monopolistic

• There is a sense of common purpose and direction,and cross-linkages and synergies are facilitated

• The product profiles being sought by PPPs are inline with global health needs

• Exploratory research and early product R&D –translational research – is supported to ensure thatpipelines are maintained

• Appropriate mechanisms are in place to ensure thecontinued and sustainable production of useful newproducts once they reach the market

• There is appropriate downstream research – transi-tional and implementation research – undertakento optimize the use of the products and provide evi-dence for policy and implementation

• Conflicts of interest are minimized• Capacity building and capacity utilization in devel-

oping countries is integrated into product R&Dactivities

• There should be strong stakeholdership from de-veloping countries within the context of productR&D, product use and product delivery.

Product development public private partnerships fordiseases of poverty. Are there more efficient alterna-tives? Are there limitations?

Executive summary

Abrief analysis of the alternatives to public privatepartnerships (PPPs) for product research and de-

velopment (R&D) for diseases of poverty is presented.At their extremes these alternatives consist of privatesector-driven and -managed R&D and public sector-driven and -managed R&D. It is concluded that theprivate sector alone will not collectively/competitivelyfully finance and manage product R&D unless thepublic sector injects many billions of dollars into cre-ating a competitive market for such products. Simi-larly, the public sector cannot endeavour alone to takeon the full role of innovators and providers of newproducts unless it is prepared to invest much moreheavily, not just in financing R&D, but also in the sus-tainable generation of a capital-intensive product R&Dinfrastructure. Such an infrastructure, which currentlyresides in the private industrial sector, is necessary toprovide any chance of sustained success in what is gen-erally recognized to be a high-risk endeavour. It is con-cluded that PPPs, despite the cross-cultural challengesof managing activities across the public and private sec-tors, offer many advantages over product R&D un-dertaken solely by either the private sector or the publicsector. This is especially the case when they are man-aged virtually with little need for additional capitalinvestment. Furthermore there is limited evidence thatthe products generated through PPPs are efficientlygenerated and highly relevant to public health needs.Thus, PPPs should be further promoted and supported.

The current environment and landscape in whichproduct R&D PPPs operate is assessed. It is noted thatthere has been a significant increase in product R&Dactivity but that this has been diverse and multi-organizational in nature. The total product R&Dactivity for diseases of poverty currently ranks at the


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IntroductionThe last several years has seen an explosion of productR&D-based not-for-profit organizations dedicated todevelop new drugs, vaccines and diagnostics for dis-eases of poverty. Many of these classify themselves aspublic private partnerships, though some engage morereadily with the private sector than others. Examplesinclude: IAVI for HIV vaccines; MMV for malariadrugs; MVI and EMVI for malaria vaccines; GATB forTB drugs; Aeras for TB vaccines; IOWH for multiplediseases of poverty; DNDi also for multiple diseases ofpoverty; Microbicides Initiative; FIND for TB diag-nostics, with possible expansion beyond TB. The vastmajority of these organizations owe their existence tofunding from a limited number of foundations andgovernment donors. By far the largest of these is theBill & Melinda Gates Foundation, though theRockefeller Foundation has also been instrumental inmany partnerships. In addition a variety of single PPPactivities have been initiated such as the developmentof a diamidine for African trypanosomiasis, funded bythe Gates Foundation, or the development of Lapdapfor malaria, funded by the UK’s DFID. For the pur-poses of this article, I may sometimes include founda-tions such as the Gates Foundation within the ‘publicsector’, in that they are not-for-profit and are provid-ing resources solely for the public good.

The PPP organizations have added to several pub-lic sector and philanthropy-based organizations andprogrammes that have long been active in this fieldand also partner with industry to deliver new prod-ucts. Such organizations include WHO/TDR (Tropi-cal Disease Research); WHO/HRP (HumanReproductive Programme); PATH (Program for Ap-propriate technology in Health), WRAIR (Walter ReadArmy Institute for Research), NIH Small BusinessResearch Grants; and other national ad hoc pro-grammes and projects. Special mention should bereserved here for the Chinese government-sponsoreddiscovery and development of the artemisinin deriva-tives. These organizations have also added to theactivities of several pharmaceutical companies that havebeen active in this field over the years, such as Merck,Roche, Aventis, GSK and Novartis, as well as numer-ous smaller companies. It is worth noting in passingthat many additional companies also have programmesrelated to improving access to specific products, rang-

ing from vitamin A to antiretrovirals (ARVs). In con-nection with product R&D the establishment of multi-million dollar drug discovery facilities by GSK (Madrid,malaria and TB), AstraZeneca (Bangalore, TB) andNovartis (Singapore, TB and dengue) should also behighlighted, as well as other industry initiatives suchas Sanofi’s malaria drug R&D programme.

With this background in mind, this paper will ad-dress two key issues:

• First, what are the alternatives to PPP? Are we cor-rect to move down the PPP road? Should weinstead, as some people have argued, focus on pro-viding financial and market (‘pull’) incentives forindustry to engage competitively in product R&D?Should we focus on developing public sector capac-ity to discover and develop, and hence own, prod-ucts and thus bypass pharmaceutical companiesaltogether?

• Second, are there limitations, or gaps, in the land-scape of the multiple organizations working todevelop new products? If so, what are they and howcan they be addressed?

Assessment of alternative options to, and uniquecharacteristics of, PPPsFor the purposes of this discussion I will define a pub-lic private partnership as a project, or portfolio ofprojects, in which public or philanthropic funds andresources are combined with pharmaceutical companyresources, in a functional partnership that is co-managed by both parties under an agreement thatstipulates the terms of that arrangement and definesthe product that is to be discovered/developed to meeta public health need.

By definition, this does not include products forwhich pharmaceutical companies identify a marketopportunity, or a strategic objective, that justifies in-dependent competitive activity. Currently antibioticsand antiretrovirals for HIV/AIDS fall into this non-PPP category.

The two extreme alternatives to PPP are: privatesector-financed and -controlled product R&D andpublic sector-financed and -controlled product R&D.I will deal with each of these in turn and finally assessthe attributes of product R&D PPPs before stating myconclusion.

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Private sector R&DI can classify two types of case where private sector-owned R&D could operate for diseases of poverty:

• First, if a company recognizes a commercial and/orstrategic and/or philanthropic motive in develop-ing a product by itself. Past examples of this includethe development of coartem for malaria by Novartisand previous cases of antimalarial drug developmentduring the 1980s and 1990s. It also applies to manydiagnostics, of which I will say more below.

• Second, if a system (perhaps legislative) is put inplace that offers sufficient (financial) incentive forcompanies to invest by themselves in developing andproducing new products for specific indications.Examples of this are not yet found in the area ofdiseases of poverty, but can be found in the marketexclusivity granted through orphan drug legislationfor rare diseases of the North and in US legislationto promote the development of paediatric formula-tions. One might also classify the concept of theGlobal Fund for AIDS, TB and malaria as a poten-tial non-legislative financial pull mechanism if thefunds were adequate in size. At the moment theyare self-evidently insufficient to have such an im-pact.

Taking the first case, history has shown that even if afew companies do take on the praiseworthy task ofdeveloping such products for limited financial gain, orfor strategic/philanthropic reasons, the collective out-put does not result in a sustainable pipeline of innova-tive new products, especially in the case of drugs andvaccines. Excluding HIV/AIDS, the closest examplewe have over the past 50 years of industry workingindependently in this manner is for malaria, and thathas obviously left us with an inadequate situation. Iwould also go further and add that the antimalarialproducts historically produced by such pharmaceuti-cal companies have not always been primarily directedat the poorest of the poor, or even if they have, thelack of public sector/academic engagement in theirdevelopment may have contributed to some of the limi-tations of those products.

Thus, malarone was developed for malaria prima-rily as a prophylactic agent. This is not to belittle theaccomplishment or the medical need for this product,but it shows that not all products for the target dis-

eases are automatically going to be of use to poorpopulations suffering from the disease. In the case ofCoartem, the product is good, but its development –through the private sector route only – perhaps con-tributed to its slow introduction into widespread use.In addition, certain initial limitations on its label anduse probably would have been averted if there had beenstronger earlier public sector engagement. Coartemintroduction was slow as the company needed, aftermarketing approval, to discuss with the public sector(in this case WHO), on the need, cost and other as-pects of its introduction. In addition, due to its (label)use as either a 4-dose or 6-dose treatment and its limi-tation to children above 10 kg, further PPP researchwith TDR has had to be carried out to validate a6-dose regimen in Africa and to demonstrate safetyand efficacy in children down to 5 kg. This informa-tion is now about to be submitted to the Swiss regula-tory agency.

No product, including one developed in PPP, shouldautomatically find its way into public sector use. Thiscan only occur if it demonstrates ‘in real life’ its supe-riority and value over other products and, in the caseof drugs, justifies inclusion on national essential drugslists. However, if a PPP-developed product has the rel-evant qualities, it often has the potential to be morereadily transitioned into use. For example, the recentlymarketed products of Lapdap (GSK – TDR) for ma-laria and miltefosine (Zentaris – TDR) for visceral leish-maniasis are now already undergoing extensivepost-regulatory investigation to provide evidence toinform policy-makers on their appropriate use.

For vaccines, where the technical hurdles are muchgreater than for drugs and diagnostics, the economicsituation relating to private sector engagement for dis-eases of poverty is similar to that of drugs. In manycases we have been fortunate that advances in vaccinetechnology directed at the North has had benefits forthe South (e.g., Hemophilus Influenzae type B vaccine,hepatitis vaccines, multi-component childhoodvaccines). However, there are cases of vaccines beingdeveloped for diseases that had potential for use in thedeveloping world, but for economic reasons, they havenot been developed for such use within the private sec-tor. A good example of this is meningitis. The menin-gitis belt across sub-Saharan Africa is not covered bythe standard vaccine of the North because it results

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from a different strain of meningococcus. A special PPPinitiated by WHO, funded by the Gates Foundationand involving several other partners is now moving thisdevelopment forward.

In the case of diagnostics, companies have investedin products for diseases of poverty, but due to smallmarket size, small diagnostics companies predominate.In addition, due to a lack of regulatory oversight, avast array of products may exist with little advice beingavailable to the consumer, or purchasing organization,on their relative value. Once again, public sector en-gagement with companies after product approval isoften necessary to enable the pubic sector to assesswhich products meet approved standards for publicsector procurement. Examples of this approach haverecently been undertaken by TDR in collaboration withWHO’s Western Pacific Regional Office to establishcriteria for the identification of malarial diagnostics thatjustify public sector procurement. Similar studies arebeing completed to establish which of the marketedsyphilis diagnostics justify public sector procurement.It is noteworthy that so far in similar studies, none ofthe gonorrhoea or chlamydia diagnostics tests havebeen declared valid for public sector procurement.There are now some PPP projects being initiated wherediagnostic products are developed in partnership froman early stage. For example, the development of a patchtest diagnostic for onchocerciasis by TDR in collabo-ration with a German company, where extensive pre-clinical and clinical testing will provide evidence ofvalue, prior to marketing and a decision by controlprogrammes on its utilization. Other tests, includingsome for TB with TDR and FIND, are at late stages ofdevelopment and once again extensive evidence willbe generated to inform the public sector in advance ofmarketing on whether or not they justify procurement.

A final word needs to be made on biotech engage-ment in product R&D on drugs and vaccines for dis-eases of poverty. Biotech companies are indeed enginesof innovation and due to their small size they can movevery rapidly in areas in which they are specialized. Thishas led many to believe that biotechs are an answer toour problem if only we can appropriately employ dili-gent use of venture capital for investment. Evidence todate has not borne out this simplistic scenario, withseveral small ‘profit venture capital’-driven initiativesfailing to take off. There are two main reasons for this.

Firstly, small biotech companies, even more acutely thanlarge companies, have to cover their costs, especially ifthey are publicly listed and owned. Secondly, theirfuture, just like that of large companies, is dependentupon making people believe that they have one or twoproducts that will earn a significant financial return.Although they can write off some R&D costs by ‘dem-onstrating’ that their technology can produce a par-ticular result or product in the ‘diseases of poverty area’,and thus gain credibility and further investment, ulti-mately such an investment is always a poor second totheir core business. Although there are plenty of ex-amples where biotech companies have ‘tested thewater’ of neglected disease product R&D through lim-ited initial investment, there are few if any cases wherethey have successfully continued to go ahead on theirown, without significant public sector support. In thecase of a few companies which have attempted this,that I am aware of, the companies are no longer inbusiness.

The second case referred to at the beginning of thissection relates to proposals that might entice the pri-vate sector to fully commit to product R&D for ne-glected diseases through the creation of financialincentives, including through legislation. There are nocases to date where this has been successfully achievedfor diseases of poverty. The bottom line is that marketsales for a product of at least US$200 million a yearare needed to justify a company investing by itself in aportfolio of drug R&D projects. If multiple productsare already on the market for a given indication, creat-ing an element of competition, this makes the likeli-hood of reaching such sales figures even less. In additionif several of those products are, or will in the futurebecome, generic, this puts further pressure on pricesand profitability. One might in such cases require atotal market size approaching US$1 billion to gener-ate competitive industrial R&D. Furthermore, due tothe political nature of the diseases in question, there isintense pressure on companies to keep their prices lowonce a product comes onto the market, further limit-ing profitability and incentive for investment.

Many ideas have been put forward to mitigate thissituation, such as orphan drug legislation providingenhanced market exclusivity; tax breaks for both R&Dand for provision of final product; and transferable cred-its for extending patent life and/or market exclusivity



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on other profitable products. However, all of theserequire intense lobbying for legislative intervention,which may differ from country to country. Once onelooks into the details of these proposals they becomeincreasingly complex and potentially difficult to manage.

The idea of a grand prize for the development of aninnovative tool such as a vaccine that meets pre-de-fined specifications has also been proposed. This seemssimplistically straightforward. However, once againwhen one looks at the detail, problems arise. For ex-ample, what if a second, superior, product is devel-oped soon after the first? Which product is put intouse? Who gets the prize? Is some sort of sharing under-taken that devalues the reward? These are interestingquestions but of course the whole idea is currentlyhypothetical because nobody has yet put up the moneyto back the idea.

I believe the bottom line is that companies will onlybe incentivized to engage competitively in productR&D if they see, and hence believe, that the publicsector is investing funds in the purchase of existingtools. If they see the billions of dollars going into thepurchase of tools that public health needs demand andthat there is substance behind the rhetoric of provid-ing increased resources, then they will invest. How-ever, given that it takes many years to develop a drugor a vaccine they will also have to be convinced thatpublic sector purchase will be sustained over the longterm. It is also likely that companies will be very fo-cused in their response. A huge increase in funds forantiretrovirals will only elicit a response for ARVs, notfor other diseases of poverty.

Even the large funds moving into public sector pur-chase of ARVs, TB and malaria have not generated anysign of increased competitive private sector R&D. Theincrease in funds has, however, stimulated further com-petition and increased ‘less risky’ private sector invest-ment in production and manufacture and improvedformulations in these diseases, particularly in thegenerics sector. This suggests that if sufficient fundswere provided to generate a strong market then inde-pendent private sector R&D could be stimulated.

In conclusion, many additional companies have be-come engaged in product R&D over the past five years.My belief is that this is only minimally due to increasedpublic sector purchasing power, or the belief that therewill in the future be such an increase. This expansion is

mainly due to increased funds and resources availablethrough product R&D PPPs to ‘push’ R&D, coupledwith an increased political awareness by companies ofthe need to demonstrate good corporate citizenship.

Public sector R&DIt is stated by some individuals and organizations thatthere should be no reliance on the private sector forthe generation of products and that the public sectorshould take a stronger lead and fully resource productR&D. In such cases it is often left open how the pro-duction, manufacture, distribution (and sale?) of theseproducts should be managed.

There are several issues that need to be assessed inaddressing this argument, over and above the philo-sophical/political arguments of the relative merits ofthe case. Philosophical and political positions equallyimpact on both free market proponents, as well as anti-free market proponents, who oppose PPPs. As there isoften little that can be said to affect these opinions, nofurther discussion of this issue is warranted in this article.

With this philosophical/political caveat I would statethe issues surrounding public sector driven productR&D are as follows: can public sector-dominated ap-proaches produce tools of the quality and standardsthat we need? Can public sector-dominated approachesproduce tools in a time-efficient and cost-effectivemanner?

There are case histories demonstrating that publicsector-managed programmes can deliver new tools thatjustify clinical use. Perhaps the best historical exampleis the case of the early vaccine industry, which was builtlargely on public sector research leading to institutes,owned by the public sector, producing and manufac-turing vaccines. However, it is notable that over re-cent years, this approach has become unsustainable,and the need for private investment to improve on ex-isting technologies has resulted in R&D-based vaccineactivities moving largely into the private sector. Theother example that springs to mind is the R&D, pro-duction and manufacture of agents related to war andnational security. Thus antidotes and vaccines againstbiological and chemical warfare agents are often de-veloped and manufactured within the infrastructure ofthe public sector.

So, public sector R&D, manufacture and produc-tion are certainly achievable. However, globally, the

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experience is that private sector-managed innovationhas resulted in more, higher quality products. Mostareas involving product R&D have therefore movedinto the private sector. This has resulted in an extremelylimited public sector infrastructure available to sup-port product R&D. Where such infrastructure exists,it is also less likely to be as modern and up to date as inthe private sector.

This lack of infrastructure and manpower in thepublic sector is highly significant. Any long term stra-tegic public/philanthropic sector approach would re-quire the provision of this infrastructure, which wouldrequire substantial and extensive capital investment. Inorder to recruit the necessary high-quality human ex-pertise, there would be a need to offer incentives forscientists and technicians on a par with the private sec-tor, further increasing costs. Furthermore, the avail-ability of expertise that projects could draw upon wouldlikely be significantly less in the public sector than inthe private sector. The choice of people, of projectsand of location where research could be undertaken,would all be substantially reduced.

In conclusion, a public sector-driven approach is ‘do-able’, but would be extremely costly and capital inten-sive, due to the need to generate and sustain anextremely complex infrastructure. It would also resultin less choice and reduced access to available expertise.Finally, there is always the added concern that if such acapital-intensive organization were placed entirelywithin the public sector, where there is also limitedexperience of governing such institutions, additionalrestrictions would inhibit progress.

Public Private R&DMuch has been written about PPPs and there is noneed to repeat the concept in detail in this paper. How-ever, I would draw out the main argumentation as totheir added value over private or public sector pro-grammes and present some limitations.

The claimed added value of such partnerships comesfrom:

• the utilization of both private sector expertise inproduct R&D and product specification, and pub-lic sector expertise in the diseases, populations ofinterest and the environments in which the prod-ucts will have to be tested and ultimately used

• the sharing of resources for an activity thus limitingthe risk to partners in both the private and the pub-lic sectors

• the sharing of existing infrastructure, limiting theneed for capital outlay

• the use and combination of best practices of man-agement, selection and review of projects from bothsectors, and to secure avoidance of conflict of interest

• the potential ease of transition of new products intopublic sector use, based on a more detailed under-standing by the public sector of the relevant meritsand faults of any given product.

The potential negative elements of public private part-nership include:

• the need to develop and operate a partnership un-der legal agreements that may involve different op-erational cultures

• complex virtual managerial structures for individualprojects.

My belief is that the positive elements outweigh thenegative, though it needs to be recognized that PPPsare not a panacea. In some cases mistakes will be madeand projects and organizations will fail, not just due toscience but also to inherent organizational and part-nership reasons.

In summary, my personal conclusion is that unlessthe public sector is prepared to invest far more funds(many billions of dollars), either to ensure sufficientcommercial ‘pull’ to get the private sector to investcompetitively in R&D or to ensure that there is a vi-able capital intensive infrastructure for public sectorR&D, then PPPs remain the only viable alternative forthe foreseeable future. I would go further and statethat even if the options were available to go down ei-ther the private sector or the public sector route, onbalance PPPs have the capacity to deliver better prod-ucts more suited to public health needs and to pro-duce and get them into use more cost-effectively.

Assessment of the current operatingenvironment of PPPsThe expansion of organizations engaging in PPPs hashad the net effect of bringing in more public sectorand philanthropic resources into product R&D for dis-eases of poverty. In the next paragraphs I will be refer-ring to some financial estimates. I should stress that



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these figures have not been closely researched, but rep-resent ‘ballpark’ estimates based on my current under-standing of what is happening in product R&D PPPsand in related activities. They need to be further re-searched and validated. However, I believe that theyare useful in transmitting to you an idea of the scale ofinvestment that we are talking about.

Back-of-envelope calculations suggest that focusedproduct R&D funding from traditional organizationssuch as TDR, HRP, PATH, NIH, USAID, WRAIR,Wellcome Trust, EU and others, including variousnationally supported projects, probably stands ataround US$50 million. The increased expenditure dueto new organizations probably adds around US$100million per year, with potential to grow to aroundUS$200 million a year over the next five years as theseorganizations further scale up. This does not count alot of ‘overhead’ input from the public sector in termsof the university and organizational infrastructure thatis also committed to these activities. It is difficult tocalculate the in-kind commitment obtained from theprivate sector in partnership projects. However, it islikely that PPP institutional funding has leveraged atleast an equivalent amount of resources from the pri-vate sector through the contribution of in-kind re-sources into projects. This is particularly the case if onecounts investment in production and manufacturing.At an extreme, in the case of TDR’s partnership withZentaris to develop miltefosine, we have calculated thatthe ratio of company to public sector investment wasgreater than 10 to 1. If one takes into account thespecific industry initiatives of GSK, AstraZeneca,Novartis and Sanofi, mentioned in the introduction,then the collective total will probably easily match thatof the public sector. Thus we are talking of a total in-crease in resources of around US$200 million per yearsince the late 1990s, with the amount possibly risingto around US$400 million in the coming five years ifcurrent trends continue. By 2010 we might be talkingof total product R&D levels for diseases of poverty,excluding HIV/AIDS drug R&D, of around US$500million.

It is critically important to realize that these fundsrepresent the input of additional personnel, peoplewhose intellect, expertise and dedication would notbe channelled into these endeavours unless these fundswere available. If one assumes an average full-time

equivalent (FTE) cost of around US$100,000 (this isa conservatively high ‘guesstimate’ based on the factthat it includes the high FTE costs of industry andwell-paid public sector individuals, combined with thelower costs of scientists, technologists, post-doctoralfellows, graduates and technicians performing muchof the work, and the increasing numbers of peopleengaged in developing countries, where personnel costsare low), then we are talking of the equivalent of 5 000or more additional FTEs of people working on prod-uct R&D for neglected diseases by 2010.

As stated at the beginning of this section, these fig-ures are extremely approximate and need further veri-fication, but they give some idea of the scale andmagnitude that we are discussing. To put this furtherinto perspective, R&D expenditure of US$500 mil-lion is about 10 per cent of that found in the largestpharmaceutical companies and 5 000 people equatesto about 25 per cent of R&D personnel found in largepharmaceutical companies.

This represents a significant body of activity, but itis characterized by its diversity and its multiplicity ofactivity. Whereas output from a single pharmaceuticalcompany is coordinated and directed, the activity de-scribed above for PPP’s comprises many individualpartnerships each with their own goals, sometimes aspart of a broader portfolio of activities and sometimesnot. This multiplicity of activity brings to it an ele-ment of confusion amongst the donor community,those involved in health policy, governments of coun-tries in which the products are to be utilized and thegeneral public. This confusion can be further exacer-bated as the general public and many of those oversee-ing the financing of health research in general oftenfind it difficult to distinguish clearly between productR&D and research in general, and often even betweendrugs and vaccines.

I list below several areas where I feel specific atten-tion needs to be paid as we move forward with ex-panding product R&D PPPs and providing theinstitutional and governance background support toensure their success.

Partnerships should be neither over-competitive witheach other nor monopolisticThere is increasing competition for funds to financePPPs and other forms of health research. This is healthy,

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especially if it results in a net increase of funds cominginto the area. However, given the relatively small levelof investment going into product R&D for diseases ofpoverty, we also need to have an environment of mu-tual support and interaction between organizations.There has been an explosion of improved and moreprofessional ‘advocacy and communication’ activities,which again has been helpful in promoting the entirearea. However, we have to be careful as a communitythat we distinguish between ‘delivery’ and ‘promise’and between ‘reality’ and ‘soundbite’. There is a needto avoid too much duplication of effort and, in thefuture, we may even be merging small organizationsinto larger ones. However, there is a need to ensurethat no one organization creates an absolute monopolyin a given area. In any sphere of life, to put all oneshopes in one single organization can result in disap-pointment. The nature of innovation demands thatthere be a multiplicity of routes by which promisingscience can be converted into new tools and that noone person, organization or committee has completeglobal responsibility for one particular area.

A sense of common purpose and direction is needed thatfacilitates cross-linkages and synergies where appropriateAs mentioned above, the product R&D activities weare discussing represent a relatively small collective ef-fort compared to the pharmaceutical industry. Just asfor a pharmaceutical company, we need to focus onand generate new products. However, as a communityinterested in product R&D for diseases of poverty weare very diverse when compared to the cohesion of asingle company. Recognizing that there are many play-ers in R&D, that there are many stakeholders in thebasic science from which product R&D is derived, andthat many more stakeholders are involved in the enduse of the products, there is a need to generate a com-mon purpose and direction in this field. A commonvision. This does not mean that there should bemicromanagement of organisations, but that thereshould be discussion and consensus around the keyelements of the types of product that we need (prod-uct profiles) and an understanding of the environmentsand health-care systems in which they will be used.Such ‘common purpose’ then makes it easier to linkbetween organizations and generate synergies.

The product profiles being sought by PPPs should be in linewith global health needIt is absolutely critical that the profiles of the productsbeing sought are in line with medical needs and thelimitations imposed on their use by human nature andsocial environments, i.e. that the products we produceare relevant for the populations for whom they are in-tended. This sounds straightforward, but it is a factorthat can often be lost within the complex technicalenvironment in which the products are generated, andwhere there is often a temptation to ‘go early with whatwe have got’, rather than to wait a little and ‘go laterwith an optimal product’. In the past, with minimalR&D investment, we in the public sector have had totake the former philosophy. With increased resourceswe can now afford the luxury of moving toward thesecond philosophy. Once again, as intimated above,there is immense value in generating a broad consen-sus on product profiles and it is an area that justifiesfurther discussion. By generating and publicizing suchconsensus we can ensure that multiple organizationsare essentially ‘pulling in the same direction’.

Exploratory research, and early product R&D –translational research – needs to be supported to ensurethat product R&D pipelines are maintainedThe focus on product R&D should not detract fromthe need to invest in the early stage research that isnecessary to ensure a full pipeline of activities and soenhance the chances of success in delivering new prod-ucts. Particularly important is the need to focus moreinvestment in the area of ‘translational research’, re-search that moves an interesting scientific observationto a stage where it justifies significant investment tooptimize it and develop it into a product for testingand clinical evaluation. In the area of drug discoverythis requires the conversion of genomic informationinto robust biochemical assays and the availability ofhigh throughput screening and other secondary ac-tivities to generate lead molecules worthy of optimiza-tion. For vaccines it may be that a particular promisingantigen requires further optimization, scale-up ofmanufacture and detailed animal testing and processdevelopment. For diagnostics it may be that an earlystage assay needs to be further optimized prior to itsdevelopment into a format that is robust, quality as-sured and ready for evaluation.



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Appropriate mechanisms need to be in place to ensurethe continued and sustainable production and distributionof useful new productsIn addition to the lack of engagement by major phar-maceutical companies in product R&D for diseases ofpoverty, there is a danger that a similar lack of engage-ment occurs in the production, manufacturing, mar-keting and distribution of products. As we moveforward with an expanded agenda, this is particularlyof concern for diagnostics and for drugs and otherproducts for the smaller diseases. If a major R&D basedcompany or a major generic company is the privatesector partner then they can utilize their vast networksof affiliates to ensure marketing and distribution. Ifsmaller companies are involved this might limit distri-bution and availability. Some interesting and innova-tive examples exist which show how such issues can beaddressed. For example, the creation of a special not-for-profit organization, the Concept Foundation, wasinitiated to handle intellectual property rights and li-censing issues associated with a new contraceptive de-veloped through WHO’s HRP. This initiative, createdwith support from the Rockefeller Foundation, hasbeen highly successful in engaging with local manu-facturers and distributors to ensure widespread avail-ability of an affordable product. Even with theengagement of major pharmaceutical companies, thereis an urgent need for complementary activity to beundertaken to enhance the number and quality of dis-pensing (pharmacy) capacities in developing countries.In many cases products are being made availablethrough local shops and markets. This is better thanno distribution at all, but given the need for appropri-ate use of drugs to ensure cure and to limit drug re-sistance, more effort needs to be directed towardsdistribution mechanisms, dispensing capacity and regu-latory oversight.

Appropriate downstream research – implementationresearch – needs to be undertaken to optimize product useand provide evidence for policyAs well as ensuring adequate research to feed into prod-uct R&D, there is equally a need to ensure that ad-equate research is done on products as they becomeregistered so that evidence is generated for optimal useand policy. This requires a different skill set to productR&D and requires a deeper understanding of health-

care systems. As new products come through PPPs wecan learn from past TDR experiences in this area; forexample, ivermectin for onchocerciasis, praziquantelfor schistosomiasis, and more recently Lapdap for ma-laria and miltefosine for visceral leishmaniasis. Each ofthese cases is slightly different, but what has been com-mon is a fairly smooth transition from product devel-opment and regulatory approval into exploration ofoptimal use and the provision of evidence for policy.This has came about because of a strong public sectorand intergovernmental engagement in ensuring thatappropriate research was undertaken and in ensuringthe implementation of research output.

Conflicts of interest should be minimizedWith the increased sums of funding involved there is aneed to ensure that selection, monitoring and reviewof projects are carried out as objectively as possible andthat those undertaking the projects are not involved inany way in the selection and review of their own work.In order to minimize any perceived and real financialand other conflicts, strict rules should be enforcedabout declarations of interest.

Capacity building and capacity utilization in developingcountries should be integrated into product R&D activitiesIn order to develop a truly sustainable system wherebynew products are effectively discovered, developed andimplemented, it is important that appropriate capaci-ties in developing countries are both developed andutilized. A sense of local ownership of data and prod-ucts greatly assists and improves the ability of coun-tries to implement new tools, methodologies andpolicies. In addition, the expansion of research capa-bilities and the generation of an appropriate research-based culture in countries results in far betterunderstanding of the options available for policy andhence better decisions on how and what to implement.For example, for product R&D projects, the utiliza-tion of developing country investigators, especially forclinical studies, can be extremely useful in ensuring thatexpertise in best practices are built into country ca-pacities in a sustainable manner. TDR and others haveplaced great emphasis in recent years on enhancinggood clinical practice (GCP) training and facilitatingthe development of capacity for ethical review withinthe context of all their product development activities.

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There should be strong stakeholdership fromdeveloping countries within the context of product R&D,product use and product deliveryProduct R&D is often about speed and technical ex-cellence. This is sometimes interpreted to mean thatusing developing country expertise or ‘building re-search capacity on the job’ is a ‘nice to have’ add-onthat can be ignored in the interest of getting a rapidregulatory approval. This is further exacerbated by thefact that almost all donor organizations are from theNorth and many of the initial recipients of their fundsare based in technical, university and industrial institu-tions in the North. These individuals, even if they haveexperience of developing country environments, mayfail to understand the long-term value and indeed thesocial responsibility to engage equally with southernpartners and to work to ensure that once a project iscompleted that there is a sustained residual capacityleft behind to undertake similar work in the future.Part of this omission occurs, I think, because thoseinvolved in the projects view regulatory approval asthe end goal. That may be the limit of their responsi-bility, but it is not why the funding has been given,nor the true goal of the projects. That goal is reachedwhen the products are used and understood by theconsumers, and are put into use within national healthsystems, whether within the private or the public sec-tor. To ensure this occurs rapidly and effectively, theparticipation of developing country scientists and in-stitutions as equal partners in development teams isessential. There are thankfully many examples withincurrent portfolios where scientists and institutions fromdeveloping countries are playing the lead role. How-ever, there is a long way to go to bring any real sem-blance of parity in this area. If developing countriesgenuinely believe they are true stakeholders then theymay also be inclined to contribute more themselves toproduct R&D projects and organizations, through bothfinancial and in-kind resources.

Concluding remarksWe have come a long way very quickly in the area ofproduct R&D for diseases of poverty and this progressdeserves to be recognized. It should also be recog-nized that this is due to the financial contributions of alimited number of public sector and philanthropicdonor organizations and in-kind contributions from alimited number of pharmaceutical companies. Both ofthese contributions and the human capital and per-sonal commitment of many individuals engaged in PPPsat the scientific and technical level should be equallyvalued.

Much of this paper has presented the big pictureand has looked at product R&D for diseases of pov-erty as a whole. However, within the indications thatare of interest, we should recognize that there remainsa great disparity between areas of major expenditureand global impact (HIV/AIDS, TB, malaria, repro-ductive health) and others of lesser expenditure andmore regional impact (e.g. dengue, schistosomiasis,filariasis, kinetoplastid diseases). A person infected withone of these latter diseases is just as important as oneinfected with the major diseases and from a humanrights and equity perspective, and as a social impera-tive, these diseases should not be left out of the PPPequation and deserve further prominence.

Finally, we are operating in a new environment withmany new players on the stage of product R&D fordiseases of poverty. As a community we need to workclosely together to ensure that we obtain maximumbenefit from this increased array of activities. We needto ensure that pipelines are maintained through en-hanced translational research and that new products,once registered, are optimally evaluated and used. Asan integral part of a successful strategy we need to en-sure we work on the diseases of interest in a mannerthat is sustainable and builds and utilizes research andother capacities in developing countries.


ANNEX 10

Donor consultation on policy andprogramming for PD PPPs1

Katherine White

Main agenda items• Key takeaways and open questions from the IPPPH’s

financing strategies meeting.• Potential areas for coordination and/or further

research by the current group of funders.

Meeting summaryThe group on the whole agreed that the PD PPPs canbe thought of as a coherent field, albeit with broaddifferences driven by the context in which they oper-ate. There was also clear recognition of the scale of thecurrent funding gap and the urgent need to exploreopportunities to increase the efficiency of supportingthe existing field, for both funders and the PD PPPs.Primary levers explored were:

• expansion of the current funding base;• implementation of consistent/comparable perform-

ance measures, and ongoing performance manage-ment based on these; and

• increasing coordination across funders and betweenPD PPPs to avoid redundancy.

The discussion covered a number of areas surround-ing the current understanding of the PD PPP field andits future needs. The main themes of this discussionare summarized in the detailed notes.

Areas for further exploration/additional workA wide range of topics were discussed as potentialfuture work that the assembled group could commis-sion. There was, however, no discussion of priorityamongst these topics, which included:

• Landscape of current and potential fudners: whoare they, what is their focus, do they have any con-straints?

Executive summaryThe consultation was attended by:

Amie Batson World BankTed Bianco Wellcome TrustRuairi Brugha Development Cooperation

IrelandDenis Carroll USAIDCharles A. Gardner Rockefeller FoundationJane Haycock UK DFIDArnd Hoeveler European Commission,

Directorate General forResearch

Hannah E. Kettler Bill & Melinda Gates Founda-tion

John La Montagne NIHJacques Laruelle BelgiumDaniel Maeusezahl Swiss Agency for Development

and CooperationOle F. Olesen European Commission,

Directorate General forResearch

Ariel Pablos-Mendez Rockefeller FoundationSue Perl Consultant, Rockefeller

FoundationPaul Spray UK DFID, ModeratorKatalijne van Diest EDCTPHarry Van Schooten NetherlandsKatherine White Consultant, Rapporteur

Garry Aslanyan (Canadian International DevelopmentAgency) and Sigrun Møgedal (Norwegian Agency forDevelopment Cooperation) were unable to attend.


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1 Convened in association with the IPPPH workshop: Combat-ing diseases associated with poverty: Financing strategies forproduct development and the potential role of public-privatepartnerships.

• Expanded/complete costing analysis for the PD PPPfield to enable a comprehensive assessment of thepotential funding gap (based on the initial back-ground paper by Adrian Towse, Jorge Mestre-Ferrandiz and Olwen Renowden, see Annex 9a).

• Mapping of how individual PD PPPs relate or couldrelate to existing global partnerships (e.g. GlobalAlliance for TB Drug Development, Roll Back Ma-laria, Global Fund to Fight AIDS, Tuberculosis andMalaria).

• Framework of potential performance metrics for PDPPP outputs and/or governance issues.

• Assessment of PD PPP potential for future deliveryof public health impacts (may also be beneficial tomap PD PPP impact on Millennium DevelopmentGoals (MDGs) or other commonly agreed publichealth targets).

• Assessment of donor coordination opportunities(e.g. existing information/resources on the field,regulatory harmonization, advocacy for the field,performance management of PD PPPs) and vehi-cles for collaboration.

Next steps• Distribute meeting materials and list of participants

to meeting attendees and invitees.• Hold follow up conference call (all invited) to de-

termine how to move forward and which areas toexplore further.

• Publish summary of donor meeting discussion andoutcome for distribution with main meeting sum-mary.

Detailed discussion by themePD PPP modelThere was general agreement that the PD PPPs are acoherent field and that the model is a sound approachto bridge the gap that has existed between blue-skyresearch and the development of new products forneglected diseases. The field is generally characterizedby:

• focus on product development; and• utilization of the principles for the private sector

model for drug development including portfoliomanagement and ensuring communication along theR&D access continuum.

However, there was also recognition of the wide dif-ferences in approach across PD PPPs as a result of:

• nuances in product development between devices,drugs, microbicides and vaccines;

• extent of portfolio model implementation; and• context in which the PD PPP is operating.

For some donors the PD PPP model offers more thanincreased product development effectiveness. They seePD PPPs as helping to raise awareness regarding ne-glected diseases and the need for investment in R&D.The challenge for the field in moving forward is tocommunicate the core strengths and perceived ben-efits of the model with simple messages that cut acrossthe current field of PD PPPs.

Different views were expressed about future growthof the PD PPP field: some saw increasing proliferationof the PPP model across this and other fields; othersbelieved that the most important opportunities aretaken (i.e. greatest social demand and scientific need).

Open questions■ Do we have the right members of the field across

PD PPPs and/or within a disease area (are theregaps and/or overlap)?

■ Should we also be considering access PPPs with thisfield or separately?

■ What benefits are the PD PPPs delivering today?How does the current set of PPPs stack up relativeto the MDGs?

■ How do we balance the need to invest in PD PPPswith other approaches to product development?

■ How do we balance the need to invest in productdevelopment and other parts of the R&D to accesscontinuum?

■ How do we balance the need to work with existingtools with the development and delivery of newtools?

Role of PD PPPs within their fieldProduct development may be the core focus of PDPPPs but many of them are also operating to greaterdegrees both upstream (translation from basic research)and downstream (ensuring delivery and use of prod-uct once delivered). The exact balance between focus-ing on product development and filling the necessarygaps on the continuum is not clear. However, donors

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do not expect PD PPPs to take direct responsibilityfor establishing delivery systems or basic research pro-grammes. If the end goal of increased public health isto be achieved, they will need to play a role in articu-lating the needs across the spectrum when gaps areidentified.

Open questions■ What role can donors play in mobilizing required

resources to ensure delivery systems are in place?■ What is the right balance between getting the prod-

uct development done and ensuring upstream anddownstream gaps are filled?

InterfacesA large part of the drug development process involvesensuring the correct communication between variousdifferent constituents during the process. There wasgeneral recognition that in some fields there are stillgaps in the links along the R&D to Access continuum.In some disease areas there was concern that moremight need to be done to ensure effective ‘translation’of basic research ideas into high potential candidatesfor development.

There was also common agreement that ensuringstrong participation from the disease endemic coun-tries early in the development process would be cru-cial for ensuring usable end products for which therewill be demand. It was suggested that there might beopportunities to increase links with the disease-endemiccountries (DECs) beyond involvement in access issuesand still maintain efficiency of the PPPs (e.g., basicresearch).

Two particular groups were identified as offeringthe PPPs additional benefits though their increasedinvolvement in the drug development process: privatedrug development companies and the DECs for whichthe drugs are being developed.

Open questions■ How do we ensure strong links between the PD

PPPs and different sources of research in their field?Are there opportunities to strengthen links with re-search in DECs?

■ How strong are the current links to DECs and PDPPPs? Is there an opportunity to increase the com-munication about existing links?

■ Can we expand industry involvement from justlearning from their models to more direct involve-ment?

MetricsWhile many of the PD PPPs have business plans andmetrics available, there does not appear to be a set ofcommonly understood metrics across the field. Therewas also recognition of the importance for the fieldthat action be taken based on the metrics to reinforcethe management rigour associated with the PPP model.

Two sets of metrics would be required: operatingmetrics to measure internal performance and outputmetrics to quantify potential public health impacts.Clear metrics for the field could benefit the PD PPPsby communicating their performance beyond the cur-rent audience. In addition the cost of assessment andmonitoring for both donors and PD PPPs will becomesubstantial without common metrics. For donors, inparticular, there is a strong desire to have output metricsfor the field that allow them to compare investment inPD PPPs with other types of investment.

Open questions■ What operational metrics are applied by PD PPPs

today? What works?■ Is there a way to quantify both social demand and

scientific maturity to enable comparison across thePD PPP field and existing tools(e.g., actuarialmethods)?

■ Can products be mapped against MDGs with a rea-sonable amount of effort?

■ When things are failing should someone go in and‘fix it’ (i.e., the fire the CEO/board model) orshould the operation be shut down?

■ Are donors willing to be disciplined and withholdfunds when performance justifies it?

FundingThere was strong agreement about the severity of thefunding gap and concerns that the current funding baseis not sufficient to sustain existing field. There was alsoa strong desire to have a clearer picture of the truefunding gap (expanding on the background paper pre-pared for the main meeting, see Annex 9a).

The group agreed that broadening the funding basebeyond traditional ‘development’ funders would re-

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quire a focused advocacy effort if PD PPPs were toreach a wider group (e.g. not all G8 involved today).On top of this, there is growing concern that the PPPfield (not just PD PPPs) is stretching the bandwidthof human resources of both existing funders and thePPPs because of the time spent educating and lobby-ing. A number of potential strategies were discussed,e.g., a letter to the G8 signed by existing supporters.In general it was agreed that none of these strategieswould be successful without clear, simple messagesabout the benefits and public health outcomes the PDPPPs could deliver. At the same time the group recog-nized that PD PPPs are not the only product develop-ment model.

Open questions■ What is the true funding gap?■ Who are potential donors and what constraints/

goals influence what they can fund?■ What role can existing funders play to help attract

additional funders?■ What is the right funding balance between PD PPPs

and other product development models?

AdvocacyThe group also believed that donors will need to ex-pand their role beyond the provision of funds. Therecould be benefit from donors working together to ad-vocate for additional support and an expanded donorbase. Donors could also collaborate with existingstakeholders on issues such as regulatory harmoniza-tion and delivery systems.

Advocacy for the PPP model would need to includewhy we believe in them, their benefits and desired endpoints. A common advocacy effort would have theadditional benefits of increasing credibility of the PDPPPs as well as potentially broadening the funding base.

Open questions■ Could the MDGs be used to help support a com-

mon advocacy message (e.g., PPPs mapped toMDGs or analysis that we won’t meet MDGs andhighlighting what new technologies could bring)?

■ How can the resources of access PPPs be leveragedto help with some of the broader advocacy issues?Do all PPPs have appropriate access PPPs to sup-port them?

■ Could the role of advocacy for the PD PPP field bebetter achieved through a coordinated effort (i.e.,donors or PD PPPs, or both)?

■ Should advocacy (for the end use of the product)be delegated to an access PPP or other entity?

CoordinationThere was strong agreement that as the field grows, itwould benefit from increased coordination among thedonors and the PD PPPs. Representatives of PD PPPspresent at the meeting strongly believed that this wouldneed to be driven by the PD PPPs themselves. Amongstthe donor group, there was a belief that at minimumdonors could benefit from a quasi-regular sharing ofinformation (e.g., assessments/studies completed).

Open questions■ What resources are available to share across donors?

Are donors already duplicating effort?■ Are there opportunities to work together on new

work to be completed (e.g., independent assess-ments)?

■ Are there common frameworks for proposals, etc.(e.g., GAVI investment framework) that could re-duce transaction costs for PPPs and donors?

Topics raised but not discussed• Product liability• Intellectual property

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ANNEX 11

Consolidation of the private partnership for productdevelopment: Africa’s role1

Ebi Kimanani, with contributions from Bartholomew Dicky Akanmori, Karniyus Shingu Gamaniel,Uford Samson Inyang, John Kilama, Andrew Kitua, Rose Leke and Kisali Pallangyo

PD PPP platform as components of an African part-nership are clinical trial facilitation, research and de-velopment of African traditional medicines and theinstitution of an African scientific and technical reviewcommittee.

‘Is there a role for investment in systemic issues?’was one of the questions that arose during the meet-ing. We feel that the answer to this question is yes,through the facilitation of clinical trials,3 and we sug-gest how to proceed. Paralleling the concerted activi-ties of PD PPPs, African product development is agrass-roots innovative effort that builds upon existinghealth-care practices using products that are familiarand accessible to the vast majority of communities inAfrica. This should be taken as a credible alternativeapproach that could benefit from the methods used byPD PPPs for fundraising, project planning and man-agement. The component on a regional technical re-view committee is an essential support action for allclinical research activities on the continent. Since theissue of ethics is fundamentally about linking the clini-cal research culture to study participant communities,we would like to play a role in defining some of thebest practices that should be in place.

Executive summary

The public-private partnership (PPP) model for de-veloping products for diseases of poverty is now well

beyond the experimental stage and needs to be con-solidated by including some core issues pertinent toits challenging mission. In the meeting organized bythe Initiative on Public-Private Partnerships for Health(IPPPH),2 participants repeatedly noted that in orderfor the PPP model to be complete, it is essential tohave broader core representation from the various con-stituencies of Africa and other regions of interest. Theparameters of this partnership component need to bedefined primarily by such representatives in collabora-tion with other key players. The seven co-authors ofthis paper cover much of the sub-Saharan region,including western and eastern, francophone andanglophone Africa. We also represent a wide range ofdisciplines and research profiles in Africa, such as tra-ditional medicine, industry, contract research organi-zations, national research institutes, academic medicalinstitutions and research networks. We would, there-fore, like to spearhead the process of defining a con-solidated platform for partnership in the productdevelopment (PD) PPP model that will add value tothe current efforts of these PPPs and address impor-tant needs of African communities. We shall start thisprocess by responding to the six key questions arisingfrom the IPPPH meeting, from the perspectives of ourvarious sub-constituencies, expertise, national govern-ments and communities. At the same time as we dia-logue with PD PPPs, we shall approach the AfricanHealth Research Forum (AfHRF) and other regionaland international forums in order to engage a conti-nent-wide consortium in the affirmation of Africanresearchers’ role in global product development.

Three key areas that we would like to bring to the

1 Prepared in response to the workshop on: Combating diseasesassociated with poverty: Financing strategies for productdevelopment and the potential role of public-private partner-ships.

2 Combating diseases associated with poverty: Financing strate-gies for product development and the potential role of public-private partnerships, Wellcome Trust, UK, April 15–16.

3 An operational plan for such facilitation has been prepared andis available for anyone who wishes to discuss this concept fur-ther and can be accessed through the IPPPH.


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Clinical trial facilitationCoordinator: Dr. Ebi KimananiThere is a need for a Compared to other componentsof PD PPPs, the facilitation of clinical trials requiresrelatively low initial investment and has many compo-nents that do not require high-tech expertise. In addi-tion, with the right kind of targeted training and systemdevelopment, clinical trials could be handled by per-sonnel trained and living in Africa. We therefore feelthat a core part of clinical trial facilitation should behandled by Africans through African institutions andthat this is a viable starting point to develop some ofthe systemic issues across PD PPPs. This can be han-dled through a research organization whose main fo-cus would be site assessment, management,coordination and general facilitation of clinical studiesin Africa. In the long run, such an organization wouldbecome a centre of excellence for clinical trials in sub-Saharan Africa. The goals of such an entity are listedbelow.

Goals• To provide a link in the present chain of drug de-

velopment in which funders and product develop-ers are primarily in the North and the patients arein Africa.

• To ensure that regions in Africa play a viable andsustainable role in clinical trials.

• To provide an opportunity for African data owner-ship.

• To play a leading role in creating guidelines to har-monize good clinical practice through the region.

• T set achievable targets for local capacity.• To develop and update an investigator/site data-

base for clinical trials in Africa with a capacity as-sessment component.

• Develop a database of Institutional Review Boardsor Ethical Review Committees and their adherenceto WHO guidelines.

Importance of collaborations of African scientific leadersKey challenges in creating such an organization (RO)in Africa include:

• Sites are located in different countries with differ-ent regulations, research and socio-economic cul-tures and levels of poverty. The ease with which one

can work in these multiple sites therefore dependson the political and economical relationship betweenthe countries. Of particular challenge will be howto work with possibly dissimilar and fragmentedregulations.

• At present, functioning sites are national researchinstitutions, each of which is mandated to serve thecountry not the region. The RO must respect andintegrate the sites’ independence into its mission andfind a creative way to organize regionally and ex-ecute nationally.

• Many of those sites are located in some of the leasteconomically developed regions in the world andbring with them the clinical care and research chal-lenges inherent in such resource-deprived settings.

Hence the support pledged to this cause by the sevenleading African participants at the IPPPH meeting is acritical element of success.

A partnership foundationThis research organization will be more than just a looseaffiliation with research sites. It must be a direct andindirect partnership with various constituencies in-volved in clinical research in Africa. These include thepatient, investigator site or clinical centre, governmentsand other regulatory authorities in each country, prod-uct developers, funding agencies and other clinical trialsponsors. The foundation of this RO must acknowl-edge, interpret and consolidate the different culturesand expectations that each of these stakeholders bringto the partnership. In order to do this effectively, thegovernance structure must legitimately represent theseconstituencies. It must also be accountable and com-petent. Emphasis should be placed on lean, well de-fined, accountable and transparent governance andmanagement structures that will be allowed to evolveas experience is gained. Starting with the sites repre-sented by the co-authors, sites will be recruited on avoluntary basis through memoranda of understandingbased on the following guiding principles:

• Respect for the separate missions of each site.• Assured flexible association that allows the sites to

work with other sponsors, networks and other re-search initiatives.

• Common strategy through operating procedures,information technology systems, etc.

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• Transparent certification criteria regarding the levelof readiness for clinical trials.

• Credible and sustainable training and capacity-build-ing systems that benefit all sites.

• Articulated expectations within and between thevarious partners.

Reception of the RO model by drug developersDrug development offers the following challenge: ex-pertise for developing drug products rests overwhelm-ingly in the commercial world; while the healthproblems of developing countries exist in a different,almost independent, and in this case African, world.Until recently, there was no tangible link between thesetwo worlds. PD PPPs were formed as a way to bridgethis gap by offering incentives through the sharing ofcosts and other resources. This proposed African ROfits in very well with this thinking, i.e., a partnershipformed to bridge the clinical trial facilitation gap be-tween Northern product developers and funding agen-cies, and African research sites and investigators. Inthis model, the required cost and other input resourcesthat go into each unit of capacity development will beestimated. Potential end users will be approached toidentify which clinical trial service they will utilize andbe requested to contribute to the development of thecapacities that go along with it. This contribution willbe either financial or in-kind support depending onthe input resource requirements. We believe that thismutual investment of resources is a more efficient andcost-effective approach for the following reasons:

• Up-front costs will be shared among many spon-sors with similar interests.

• Each potential site will interact with one organiza-tion, thus avoiding duplication of processes.

• Potential site competition will be avoided.• Negotiations for partnerships will be based on this

model. Examples of hypothetical partnership agree-ments are given in Appendix 1.

It is our view that an African research organization,which aims to assess, manage and coordinate sites dur-ing clinical trials, is a specific, feasible and meaningfulcontribution from African players in the PD PPPs. Inaddition it is a cost-effective opportunity to invest insystemic issues that cut across PPPs.

Traditional medicinesCoordinators: Prof. Karniyus Gamaniel, Dr. Uford Inyang,Prof. Kisali PallangyoIn many countries in Africa, the ratio of orthodoxmedical practitioners to the general population is about1:2000 while that for traditional health practitionershas been estimated at 1:200. Traditional African medi-cines (TAMs) are thus accessible, affordable, availableand acceptable to Africans. TAMs need to be devel-oped through standardization, safety and clinical evalu-ations, registration, marketing and official recognitionwith appropriate structures for regulating the qualityof TAM products. In addition to these usual challengesto drug discovery and development, searching for andharvesting the candidate plants have to be approachedin an environmentally sensitive and sustainable man-ner. The appropriate development of TAMs poses achallenge to many governments in Africa, which none-theless appreciate the importance of traditional ap-proaches to health care. The Nigerian government setup the National Institute of Pharmaceutical Researchand Development (NIPRD) exclusively to harness, dis-cover and develop TAMs. Cameroon’s Institute ofMedical Research and Studies of Medicinal Plants(IMPM) and the Institute of Traditional Medicine inTanzania are other examples of the recognition of theimportance of this approach by governments in theregion. We would like to consider the extent to whichthe experiences and operational procedures of PD PPPscan be applied to the development of TAMs with a viewto fostering research and manufacturing partnerships.

Examples of activities to be initiated• Continent-wide inventory of the numerous plant

species with potential for medicinal uses.• Standardization of research methods.• Development and harmonization of regulatory and

ethical requirements.• Advocacy and awareness campaigns.• Education of international community.

Importance of collaborations betweenAfrican scientific leadersIn order to institute sustainable TAM practices, theabovementioned goals can only be meaningfully ad-dressed by scientific partnerships in all sub-regions ofthe continent. Given that the African participants to

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the IPPPH meeting span western and eastern Africa,orthodox and traditional medicines, and clinicalresearch including product development, their endorse-ment of this initiative is critical for placing TAM onthe PD PPP agenda.

African scientific and technical review committeeCoordinator: Prof. Rose LekeTo date, the prevailing wisdom has been to make clini-cal trial applications for phase I trials through regula-tory authorities in the United States and Europe, andthen to go ahead with phase II and higher trials at thedeveloping country site. A prerequisite for these siteshas been the establishment of IRBs and training of theirmembers so that they will be able to review the ethicalaspects of the trial for the developing country trial site,and to monitor its progress to ensure compliance with

good clinical practice. In some cases these IRBs havebeen accredited by the US National Institutes ofHealth. This work is important and basic, and mustcontinue. The big problem with this approach is thatit is completely driven from the outside. Since the is-sue of ethics is where science meets the people, we feelthat in the case of African communities, the primarylink should be by individuals who have their roots inthe African village or community and have had suffi-cient exposure to science, clinical research and othercultures, especially Western culture. Such individualsare conversant with both cultures in fundamental waysthat go beyond language alone and have credibility in– and hence are accountable to – both communities.

We would like to do this within the InternationalScientific and Technical Review Committee (ISTARC)which is being facilitated by Dr. Julie Milstien of WHO.

APPENDIX 1. HYPOTHETICAL EXAMPLES OF THE APPLICATION OF THE PARTNERSHIP MODEL

Sponsor’s Sponsor’sProject Sponsor RO’s responsibility responsibility Research team Physical facilities contribution

Phase III HIV International Site and investigator GLP and GCP training; Principal investigator; two Examination rooms; 40% tomicrobicide trial. research recruitment; regulatory purchase all co-investigators; one laboratory; drug overallEffectiveness, organization, requirements; ethical equipment for the research coordinator; four storage; document phase Iplacebo- PPP submission; informed study including lab, study nurses; three lab storage and archiving; budgetcontrolled, 2000 consent; community computer hardware technicians; four field administrative space.participants, four- outreach; subject and communication; assistants; one HIV/AIDSyear study. recruitment and follow- renovate study facility counsellor; one adminis-

up; drug importation, including lab and trative assistant; onestorage and dispensing; subject interview and accountant; threeadverse event reporting; examination rooms. auxiliary staff.project management; Allow one yeardata collection and entry. preparatory period.

Phase II/III Pharma Clinical monitoring; GCP training; One project manager; Storage; 7.5%efficacy, two-arm, company, regulatory affairs; ethical purchase essential lab one research coordinator; administrative space.standard therapy Industry review submission; site equipment; communi- three study nurses;comparator, 300 identification and cation and computer three monitors; threemalaria patients, management; drug hardware. field assistants; onesix-month study. importation, dispensing administrative assistant;

and accountability; one accountant;project management. three auxiliary staff.

Phase III HIV International Principal investigators; GLP and GCP training; Principal investigator; Examination rooms; 10%microbicide trial. research regulatory requirements; purchase all equipment one research coordinator; laboratory; drugEffectiveness, organization, ethical submission; for the study including two study nurses; two lab storage; documentplacebo-controlled, PPP informed consent; lab, computer hardware technicians; two field storage and archiving;250 participants, community outreach; and communication; assistants; one HIV/AIDS administrative space.two-year study. subject recruitment and renovate study facility counsellor; one

follow-up; drug impor- including lab and administrative assistant;tation, storage and subject interview and one accountant; twodispensing; adverse examination rooms. auxiliary staff.event reporting; projectmanagement; datacollection and entry.

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APPENDIX 2. EXAMPLES OF SERVICES AND CAPACITIES

Services Required human resources

DATA MANAGEMENT

• Design, handling and storage of case report forms • Database programmers sensitive to regulatory requirements• Database design • Data entry clerks• Medical coding • Record and data archivists• Data entry and verification • Quality control/assurance professionals• Quality control/assurance• Internet data collection

BIOMETRICS AND EPIDEMIOLOGY

• Protocol development • Statistical programmers• Study design • Biostatisticians• Sample size estimation • Epidemiologists• Statistical analysis plans • Medical writers• Data analysis/statistical and other reports• Epidemiological studies

SITE ASSESSMENT AND MANAGEMENT

• Site identification: facilities, staff • Clinical research associates• Research staff qualification • Regulatory personnel• Investigators’ meetings • Quality control/assurance professionals• Project tracking • Project managers• Essential documents • Documentation specialists• Site auditing• Regulatory guidelines• Ethical review procedures• Level of readiness for clinical trials

INVESTIGATOR SITE DATABASE

• Site location and access using GIS1 • Database designers and programmers• Investigator biodata and research experience • GIS experts• Estimated prevalence of disease

1 GIS = Geographic Information Systems


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Principal Authors

Roy WiddusKatherine White


The aim of the Initiative on Public-Private Partnerships for Health is to increasethe effectiveness of public-private collaboration, particularly by helping thoseseeking to develop health products, or to improve access to such productsneeded to fight neglected diseases and other health problems in developingcountries.

Created in 2000 in Geneva, Switzerland, the Initiative on Public-PrivatePartnerships for Health is sponsored by the Bill & Melinda Gates Foundation,the Rockefeller Foundation and the World Bank. It operates under the aegisof the Global Forum for Health Research, an independent internationalfoundation helping to correct the 10/90 gap in health research, from which italso receives support (www.globalforumhealth.org).

www.ippph.org

Initiative on Public-Private Partnerships for HealthInternational Center Cointrin • Block G • 3rd Floor • 20, route de Pré-Bois

PO Box 1826 • 1215 Geneva • Switzerland

Tel: (+41 22) 799 4086/4073 • Fax: (+41 22) 799 4089E-mail: [email protected]

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