1-4d Qualiy-Risk-Management

Tony Gould

Quality Risk Management

2 | PQ Workshop, Abu Dhabi | October 2010

Introduction

Risk management is not new – we do it informally all the time

Military Standard 1629 dated 1974 regarding formal risk management

Risk management has been used in the medical device, telecommunications, aerospace and car industries for many years


Introduction Risk management has also been part of the pharma industry for many years:– GMP requirements are designed to address risk. For example, the specific GMP requirements for sterile products are designed to mitigate the risk of sterility failure

– In some cases, GMP specifies a risk based approach. For example, "a risk assessment approach should be used to determine the scope and extent of validation required" (WHO Annex 4, 5.2.10)

– Specifications in pharmacopoeial monographs include tests for known potential contaminants


Introduction Greater use of risk management tools in the future

We must accept this and prepare From a GMP point of view, we are only concerned with risks associated with quality, safety and efficacy – quality risk management

Organisations use risk approaches in other areas, e.g. to ensure resources are utilised in the most effective way. Also applicable to inspectorates


GMP requirement A system for quality risk management should be included in the quality assurance system

Quality risk management is a systematic process for the assessment, control, communication and review of risks to the quality of the medicinal product. It can be applied both proactively and retrospectively.

The quality risk management system should ensure that:– the evaluation of the risk to quality is based on scientific knowledge, experience with the process and ultimately links to the protection of the patient; and

– the level of effort, formality and documentation of the quality isk management process is commensurate with the level of risk. 1.2 – 1.5


QRM - the dangers

There is a desired outcome and risk management is used to justify it

Invalid assumptions – suit the desired outcome

Cost reduction (increased profits) is often the real reason that many risk assessments are done– Cost reduction may be a secondary outcome

Variable tolerance of risk


QRM – from an inspectors point of view

Be prepared so that the process is understood Have sufficient knowledge to understand what has been done and challenge assumptions, omissions etc

Be clear about when QRM is not appropriate Be flexible and accept the outcome of a scientifically sound QRM exercise

If done properly there should be increased assurance of quality (and possibly cost savings)


What is QRM

"Quality Risk Management is a systematic process for the assessment, control, communication and review of risks to the quality of the medicinal product across the product lifecycle." (ICH Q9)


Typical QRM process

What might go wrong or has gone wrong?

What is likelihood or probability?

What are the consequences (severity)?

What is the level of risk? Any mitigating factors?

Risk Review

Risk Com

municatio

n

Risk Assessment

Risk Evaluationunacceptable

Risk Control

Risk Analysis

Risk Reduction

Risk Identification

Review Events

Risk Acceptance

InitiateQuality Risk Management Process

Output / Result of theQuality Risk Management Process

Risk Management tools


Risk assessment

"A systematic process of organizing information to support a risk decision to be made within a risk management process. It consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards." (ICH Q9)


Risk assessment terms

Risk identification– Use of information to identify hazards or potential risks

– Historical data, theoretical analysis, informed opinions

Risk analysis– Estimation of risk associated with identified hazards

– Qualitative or quantitative– Links probability and severity– In some tools, includes detectability


Risk analysis - probability

A simple qualitative tool:

P – Probability of OccurrenceHigh Likely to occur

Medium May occurLow Unlikely to occur

Remote Very unlikely to occur


Risk analysis - severity

A simple qualitative tool:S – severity level if event occursCritical Serious GMP non-compliance

Patient injury possible

ModerateSignificant GMP non-complianceImpact on patient possible

Minor Minor GMP non-complianceNo patient impact


Risk assessment terms

Risk evaluation– Compares identified and analysed risk against criteria

– Considers probability, severity and detectability

– Output can be qualitative (high, medium or low)

– Output can be quantitative (probability x severity x detectability)

– Quantitative provides a relative ranking – prioritises risk


Risk evaluation

A simple risk table with risk acceptability criteria:Risk = P x S

SeverityProbability

Minor Moderate Critical

High Unacceptable risk

Intolerable risk

Intolerable risk

Medium Acceptable risk

Unacceptable risk

Intolerable risk

Low Acceptable risk

Acceptable risk Unacceptable risk

Remote Acceptable risk

Acceptable risk Acceptable risk


Risk evaluation Modify evaluated risk according to existing detection controls

Detectability:– High – the control is likely to detect the negative event or its effects

– Medium – the control may detect the negative event or its effects

– Low – the control is not likely to detect the negative event or its effects

– Zero – no detection control in place


Risk evaluation

Risk definitions:

Intolerable – work to eliminate the negative event or introduce detection controls is required as a priority

Unacceptable – work to reduce the risk or control the risk to an acceptable level is required

Acceptable – the risk is acceptable and no risk reduction or detection controls are required


Risk control

"Actions implementing risk management decisions" (ICH Q9)– Includes risk reduction (if applicable) and risk acceptance


Risk control terms

Risk reduction– Actions taken to lessen the probability of occurrence of harm and the severity of that harm

– Typically CAPA and change control Risk acceptance

– The decision to accept risk– If risk reduction action taken, follows re-analysis and evaluation


Risk Review

"Review or monitoring of output/results of the risk management process considering (if appropriate) new knowledge and experience about the risk." (ICH Q9)– Ensures nothing has changed to affect the QRM assumptions, output and conclusions

– Consider during product review


QRM tools – some of them! Basic risk management facilitation methods

(flowcharts, check sheets etc.); Failure Mode Effects Analysis (FMEA); Failure Mode, Effects and Criticality Analysis

(FMECA); Fault Tree Analysis (FTA); Hazard Analysis and Critical Control Points (HACCP); Hazard Operability Analysis (HAZOP); Preliminary Hazard Analysis (PHA); Risk ranking and filtering; Supporting statistical tools.


Potential applications Quality Management (e.g. self-inspection, training,

complaints, deviations, change control) Development (ICH Q8) Facilities, Equipment and Utilities (e.g. design,

qualification, hygiene, calibration, computers) Materials Management (e.g. supplier assessment,

storage) Production (e.g. validation, in-process sampling and

testing) Laboratory Control and Stability Studies (e.g. OOS,

retest periods, validation) Packaging and Labelling (e.g. package design, label

control)

1-4d Qualiy-Risk-Management

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