Nanomedicine: Nanotechnology, Biology, and Medicinexx (2013) xxx–xxx

nanomedjournal.com

Continuing to strengthen FDA's science approach toemerging technologies

Rachael Anatol, PhD, Steven Bauer, PhD, Suzanne Epstein, PhD, Ross Filice, MD,Kristina Lauritsen, PhD, Mark H. Lee, PhD, Elizabeth Mansfield, PhD,

Michelle McMurry-Heath, PhD, Joseph Milone, PhD, Carlos Peña, PhD⁎,Steven Pollack, PhD, Issam Zineh, PharmD, MPH, FCCP

Emerging Technology Programs, Office of the Commissioner, Food and Drug Administration, Silver Spring, MD, USA

Received 1 March 2013; accepted 11 April 2013

Abstract

Emerging technologies result when advances and innovation in technology lead to discoveries. Often emerging technologies stimulatenovel research in medical product development that contribute to new approaches to manufacturing and can improve the quality of products.By supporting investments in agency coordination, staff training and professional development, regulatory science research, stakeholderengagement, and enhancing opportunities for expert input, the U.S. Food and Drug Administration plays a critical role in translatinginnovations into novel safe and effective medical products that improve the public health.© 2013 Published by Elsevier Inc.

Key words: FDA; Science; Emerging technologies

Emerging technologies result when advances and innovation in knowledge and understanding of science, active engagement

technology lead to discoveries. Often emerging technologiesstimulate novel research in medical product development thatcontribute to new approaches to manufacturing and can improvethe quality of products for consumers.1,2 The U.S. Food and DrugAdministration's (FDA) mission is to protect the public health byassuring the safety, effectiveness, quality, and availability of a widerange of products3 includingmedical products that can incorporateemerging technologies. FDA regularly evaluates the combinationof promise, risk, and uncertainty inherent in new products andtechnologies.4 In doing so, the Agency continues to take steps tofoster responsible development of innovativemedical products andprovide regulatory clarity to industry, which is critical to FDA'smission.5

FDA's ability to support the responsible development ofemerging technology products requires application of relevantlaws, regulations, and guidance. Equally critical is the

⁎Corresponding author.E-mail address: carlos.pena@fda.hhs.gov (C. Peña).

1549-9634/$ – see front matter © 2013 Published by Elsevier Inc.http://dx.doi.org/10.1016/j.nano.2013.04.005

Please cite this article as: Anatol R., et al., Continuing to strengthen FDA's sciehttp://dx.doi.org/10.1016/j.nano.2013.04.005

of FDA's expert scientific staff, and building a stronginfrastructure (collectively referred to as FDA's sciencecapacity) to guide science-based and science-led decisionmaking. A strong science capacity not only ensures theAgency's ability to review products incorporating the latesttechnology, but also prepares the Agency for future submissions.In this article, we discuss emerging technologies and a few of theAgency activities that help facilitate the development ofproducts derived from emerging technologies including: 1)establishing lines of communication; 2) coordinating andmaking transparent agency activities; 3) creating opportunitiesfor staff training and professional development; 4) supportingintramural and collaborative regulatory science research; and 5)engaging external stakeholders through workshops, advisorycommittees, and other mechanisms.

What are some emerging technologies?

Emerging technologies represent groundbreaking advancesand innovation in technology, may provide tools to solve

nce approach to emerging technologies. Nanomedicine: NBM 2013;xx:1-6,

Table 1FDA science activities in emerging technologies across the agency.

* All Centers and Offices includes the Center for Biologics and Evaluation and Research (CBER), Center for Drug Evaluation and Research (CDER),Center for Devices and Radiological Health (CDRH), Center for Food Safety and Applied Nutrition (CFSAN), Center for Tobacco Products (CTP), Center forVeterinary Medicine (CVM), National Center for Toxicological Research (NCTR), Office of the Commissioner (OC), and Office of Regulatory Affairs (ORA).

2 Continuing to strengthen FDA's science approach to emerging technologies

previously unresolved or challenging problem, and by theirnature, are constantly evolving. In some cases, emergingtechnologies have the potential to lead to better health outcomes,lower costs, and earlier access to more effective treatments. In2007, FDA leadership requested the Advisory Board to theCommissioner of Food and Drugs (Science Board) to perform areview and assess whether knowledge and understanding ofscience and technology at the FDA supports both current andfuture regulatory needs. At that time, the Science Board identifiedseveral emerging technology areas that they deemed the mostchallenging to the FDA.6 The areas identified are: combinationproducts, genomics/proteomics (also referred to as systemsbiology); imaging; medical device innovation (including wirelesshealthcare devices and robotics); nanotechnology; and regener-ative medicine (including cell- and tissue-based products).

In their report, the Science Board recognized that someemerging technologies such as combination products, nanotech-nology, and regenerative medicine may apply to multipleproduct categories (drugs, devices, biologics, etc.), and thus,necessitate intra-agency staff communication and coordinationwith public stakeholders. For other topic areas of medical deviceinnovation, such as wireless technologies and robotics whererelated products may be addessed primarily by a single agency

component, the Science Board suggested that the Agency seek acombination of enhanced intramural regulatory science researchand external input to make sure it is knowledgeable and aware ofthe latest advances in the field.

Science based approaches to emerging technologies at FDA

The FDA regularly evaluates products of emerging technol-ogies, including the categories identified by the Science Boardand has taken several steps to support such products at theAgency (see Table 1). For example, FDA formed a Task Force in2006 to help assess questions related to FDA's regulation ofproducts that may contain nanomaterials or otherwise involve theapplication of nanotechnology. By 2010, several efforts evolvedinto a coordinated nanotechnology regulatory science programfocused on enhancing staff training, core facilities for regulatoryscience research, and coordinated science-based activitiesconcerning the regulation of nanotechnology-based products.7

Establishing lines of communication

FDA is an agency within the U.S. Department of Health andHuman Services that consists of the Office of the Commissioner

3Continuing to strengthen FDA's science approach to emerging technologies

and four directorates overseeing the core functions of the agency:(1) Medical Products and Tobacco, (2) Foods and VeterinaryMedicine, (3) Global Regulatory Operations and Policy, and (4)Operations. In line with the importance of communication acrossFDA directorates and prior recommendations of the 2007 FDAScience Board Report, in 2011 FDA convened a working groupof experts from across the agency to evaluate FDA scienceactivities supporting the applications of emerging technology tomedical products. The goals of the working group are thefollowing: create a place for information exchange on emergingtechnology-related activities; examine opportunities to advancethe agency's preparedness to usher in new technologies,especially when an approach at the agency for one topic areamay be relevant to additional areas; and continue to evaluateregulatory science approaches and tools to further aid in specifictopics areas. The working group identified the following themesto advance emerging technology products: agency communica-tion; coordination and transparency; staff training and profes-sional development; regulatory science research; stakeholderengagement; and building new mechanisms for obtainingexternal expert input. For some themes, the agency employed acentralized approach towards addressing emerging technologiesby enhancing coordination of the agency's efforts in emergingtechnologies (also see Table 1). Other areas are addressed byCenter-specific approaches and are more focused on theregulatory responsibilities of the Center.

Agency coordination and enhancing transparency

Agency coordination and transparency is important for FDAto use its limited resources efficiently and effectively to addresscross-cutting issues arising from the regulation of emergingtechnologies. Specifically, FDA developed a Strategic Plan forRegulatory Science in 20111 that identified eight priority areaswhere new or enhanced engagement is essential to the continuedsuccess of FDA's public health and regulatory mission. Withinthis plan, emphasis is given to coordinating regulatory scienceefforts for emerging technology product areas, includingenhancing communication and cooperation among staff, andsharing scientific expertise within the Agency. The plan alsoidentified staff training and regulatory science research toaddress scientific gaps and challenges posed by novel products.

For example, in the area of Regenerative Medicine, intra-agency efforts exist to promote coordination within the FDA8

such as the Multi-Center Fellowship in Regenerative Medicinewhich is an integral part of the FDA Commissioner's FellowshipProgram (CFP). The fellowship was established in 2008 to attractnew talent to the agency.9 Regenerative Medicine Fellows workin both the Center for Biologics Evaluation and Research(CBER) and the Center for Devices and Radiological Health(CDRH) to facilitate cross-center collaboration and conductresearch under the mentorship of FDA senior scientists as well asorganize scientific seminars from which FDA staff may learn thelatest advances in regenerative medicine from both agencypersonnel and external experts.

Improving the transparency of the agency's efforts to theoutside is also important. Since 2010, FDA has launched anumber of web resources to address topic-specific questions

involving intra-agency coordination, such as with combinationproducts10 and other efforts to open the doors of the agency.11

The Microarray Quality Control (MAQC) project is anotherexample of working with the research community to addressthe technical performance of emerging technologies, such asmicroarray and next-generation sequencing to prepare the FDAfor review of these types of data.12 Further examples includeFDA's webpages on genomics13 and nanotechnology,14 andCBER's Office of Cellular, Tissue, and Gene Therapies'(OCTGT) web-based educational series, “OCTGT Learn”,which provides standardized regulatory information forstakeholders.15

Staff training and professional development

Staff training and professional development is essential tokeep pacewith increasingly complex and innovative products andtechnologies, and to respond rapidly and effectively to publichealth emergencies.16 To address these needs, the agency hasinvested significantly in staff training programs, at both theAgency level and at the Center-level. At the Agency level, FDAhas taken a comprehensive approach to addressing emergingtechnologies. For example, FDA launched the New Frontiers inScience Lectureship Program, co-sponsored by the HealthResearch Alliance.17 The focus of the lectureship series isemerging technologies and it provides seminars on topicsassociated with emerging technologies, such as ethics. Similarly,the agency has increased the number of opportunities forcontinuing education of FDA staff through partnerships withthe National Institutes of Health, Centers for Disease Control andPrevention, and academic sites like Maryland's Center forExcellence in Regulatory Science and Innovation (CERSI).18

The Maryland CERSI has a program for education and training,with a project area focusing entirely on emerging technologies.19

Approaches that cultivate more specific coursework foremployees with an interest in a particular product ortechnology sector are also available at the Center level.These efforts can range in format from small seminars to fulllectures, to entire courses.

Regulatory science research

For FDA to support innovation and the development of newtechnologies, the Agency must also engage in enhancing itsown knowledge and understanding of new science. One waythis happens is through regulatory science research, the scienceof developing new tools, standards, and approaches to assessFDA-regulated products. The Centers carry out the majority ofregulatory science research related to emerging technologiesrelevant to their product areas. For example, the Center forDevices and Radiological Health (CDRH) has funded aninteragency agreement with the National Institute of Standardsand Technology (NIST) to generate publicly available referencematerial of human genomic DNA.20 This reference materialwill be highly characterized genomes used to evaluatetechnology performance, develop novel technologies, and toincrease knowledge about genomes. Additionally, under theMedical Countermeasures Initiative, a separate funded agree-ment has been created to generate similar types of reference

4 Continuing to strengthen FDA's science approach to emerging technologies

materials of microbes, relevant to the topics of genomics andproteomics.1

In other emerging technology areas such as nanotechnology,regulatory science research has enabled FDA to evaluatematerials measured in nanometers that may be used in a rangeof products, including drugs, devices, and cosmetics. Forexample, studies led by the Center for Drug Evaluation andResearch (CDER) assessed potential risks associated withincreased dermal penetration of small particles used insunscreens.21 Those studies found no significant penetrationthrough intact skin of titanium dioxide from sunscreenformulations containing nano- and submicron-size titaniumdioxide particles. The methods developed and used in thesestudies are also important to evaluating products that may usesimilar sized materials. In the regenerative medicine space,current activities such as the Mesenchymal Stem Cell (MSC)Consortium were formed as research collaboration betweenmultiple CBER principal investigators.22–24 MSC-based cellulartherapies are being widely evaluated in clinical trials and areconsidered to hold great potential for treatment of a wide array ofmedical conditions. However, the medical utilization of MSCs(and stem cells, in general) is novel and product characterizationis particularly challenging. Current characterization of humanMSCs relies mostly on a few cell surface markers and qualitative,relatively imprecise measures of cell activity. In general, thesecharacteristics have not successfully predicted clinical effective-ness. The research goal of the MSC Consortium is to develop cellcharacterization methods that can be used to predict quality,potency, and safety of MSCs. The methods developed by theregulatory science program will be made publically available andis expected to facilitate development of cell-based regenerativemedicine products.

Additional examples of regulatory science research inemerging technology areas include: (1) FDA staff collaboratingwith the Defense Advanced Research Projects Agency onassessing medical device innovation (e.g., through the develop-ment of artificial limbs and on investigating ways to increasetheir safe and effective use over time25) and (2) FDA's study onmedical imaging, with an emphasis on the amount of radiationpatients are exposed to during diagnostics imaging tests, anddeveloping strategies to minimize their exposure.26

Engaging the public and other stakeholders

In addition to FDA's expert scientific staff and stronginfrastructure, FDA website updates, public meetings, and otherforms of outreach, the engagement of outside experts alsocontributes to making FDA activities more transparent, as wellas providing important intellectual resources of additionalexpertise to FDA. FDA continues to work with stakeholdersinterested in emerging technologies, including consumers,industry groups, non-profit organizations, and academia, in abroad range of activities and efforts, including the developmentof guidance documents and performance standards, andconsumer updates.27

A primary source of external input to the agency is itsAdvisory Committees. The FDA works with more than 50committees and panels to obtain independent expert advice on

scientific, clinical, and policy matters28 as well as input's fromconsumer and patient advocacy groups, manufacturers, andadditional stakeholders. The committees are established toprovide support to the FDA's mission of protecting andpromoting the public health, and meet requirements set forth inthe Federal Advisory Committee Act.29 Often, the FDAobtains advice from its Advisory Committees on topics thatpertain to emerging technologies. For example, FDA regularlyupdates its Science Board Advisory Committee on theagency's latest scientific efforts that support the regulation ofnanotechnology.7

Establishing additional opportunities to foster greater inter-action and dialogue with external stakeholders is a priority at theAgency. These opportunities may include online resources,webinars, publications, presentations, public meetings, andinteractions with other federal agencies. Public meetings suchas workshops and other forums where FDA can engagestakeholders on specific issues represent additional opportunitiesfor FDA to receive input. For example CDRH's Office of InVitro Diagnostics and Radiological Health has convened anumber of public meetings on questions related to a variety ofmedical device innovation topics including analytical validationof next-generation (ultra-high-throughput) sequencers,30 modelsfor validation of highly multiplexed nucleic acid technologies inmicrobiology and medical countermeasures uses,31 and clinicalapplication and scientific and technological challenges associat-ed with performance validation of medical countermeasureradiation biodosimetry devices.32

FDA has also engaged the public through innovativeinformation exchange mechanisms such as the VoluntaryExploratory Data Submission (VXDS) program, a non-regula-tory, flexible mechanism for scientific exchange between FDAand external scientists (e.g., industry scientists, academicresearchers).33,34 Under this exchange, participants benefitfrom an enhanced understanding of scientific issues withpotential relevance to public health or therapeutic productdevelopment. The scope of VXDS meetings includes (but is notlimited to) scientific discussions of (pharmaco) genetics/genomics, innovations in trial designs and methodology, andemerging technologies. The VXDS program allows for insightinto current FDA thinking about exploratory data that may assistin reaching important strategic decisions and potential time-savings with an annual average of five submissions.35 Thesecollaborative regulatory science research investments at theagency help foster a robust regulatory science and educationalculture that enables FDA to address the scientific challengespresented by revolutionary new developments in medicalproducts, as well as allow for the examination of other topicareas important to FDA.

Developing a network of experts

The agency is developing novel tools to gather expert inputon areas of emerging scientific need and enhance its approach toemerging technologies. The recent successful pilot of theNetwork of Experts (N of E) program conducted by CDRHrepresents an initiative to enhance premarket consultativeresources for submission review.36 Through this program the

5Continuing to strengthen FDA's science approach to emerging technologies

Agency partners with leading scientific and clinical societies tobuild a knowledge bank of leading, external regulatory scienceexperts. Scientists and reviewers within the Agency are then freeto pose questions to the N of E or obtain a list of scientists withrelevant expertise vetted for conflict of interest, willing to honorconfidential information, and scientific stature in as little as 2weeks, which is much faster than identifying experts and vettingthem for conflicts of interest at the time of need. In doing so, theN of E program gives FDA scientists an additional resourcefor rapid access to cutting edge science, something that is criticalto building the Agency's capacity to respond to emerging fieldsof science.

Looking ahead

Realizing the promise of emerging technologies not onlyrequires continued research and development, but appropriateand balanced regulation and oversight.6 There is need tocontinually enhance effective regulation of emerging technolo-gies, and bring regulatory clarity to those who develop novelproducts, while ensuring products are safe, and as appropriate,effective. Toward this goal, regulatory agencies, including FDA,have invested in their staff and scientific infrastructure, reachedout to multiple stakeholders, to help make sure decisions arebased on the best available scientific evidence.

FDA intends to continue to make investments in its scientificcapacity and enhance coordination in emerging technology topicareas that may cross multiple products or applications.Importantly, FDA intends to engage relevant stakeholdersearly and often to receive the best input on practical approachestowards realizing the benefits of, while minimizing risksassociated with, emerging technologies. By targeted investmentsin agency coordination, staff training and professional develop-ment, regulatory science research, stakeholder engagement, andenhancing opportunities for expert input, FDA looks forward tohelping speed innovations that make medical products more safeand effective for the consumers and, ultimately, protect andpromote public health.

Appendix A. Supplementary data

Supplementary data to this article can be found online athttp://dx.doi.org/10.1016/j.nano.2013.04.005.

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