Quality Risk Management Tony Gould

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 R i s k C o m u n c a t Risk Assessment Risk Evaluation unacceptable Risk Control Risk Analysis Risk Reduction Risk Identification Review Events Risk Acceptance Initiate Quality Risk Management Process Output / Result of the M g e l

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 Risk analysis 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 Occurrence Likely to occur High May occur Medium Unlikely to occur Low Very unlikely to occur Remote

Risk analysis - severity A simple qualitative tool: S – severity level if event occurs Serious GMP non-compliance Patient injury possible Critical Significant GMP non-compliance Impact on patient possible Moderate Minor GMP non-compliance No patient impact Minor

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 Risk = P x S A simple risk table with risk acceptability criteria: Risk = P x S Critical Moderate Minor Severity Probability Intolerable risk Unacceptable risk High Acceptable risk Medium Low Remote

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 Risk acceptance 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)