audit 1 4d qualiy risk management
TRANSCRIPT
Tony Gould
Quality Risk Management
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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
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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
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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
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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
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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
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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)
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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)
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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
Ris
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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 M
anagement tools
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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)
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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
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Risk analysis - probability
A simple qualitative tool:
P – Probability of OccurrenceHighLikely to occur
MediumMay occur
LowUnlikely to occur
RemoteVery unlikely to occur
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Risk analysis - severity
A simple qualitative tool:
S – severity level if event occurs
CriticalSerious GMP non-compliancePatient injury possible
ModerateSignificant GMP non-complianceImpact on patient possible
MinorMinor GMP non-complianceNo patient impact
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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
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Risk evaluation
A simple risk table with risk acceptability criteria:
Risk = P x SSeverity
ProbabilityMinorModerateCritical
HighUnacceptable riskIntolerable riskIntolerable risk
MediumAcceptable riskUnacceptable riskIntolerable risk
LowAcceptable riskAcceptable riskUnacceptable risk
RemoteAcceptable riskAcceptable riskAcceptable risk
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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
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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
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Risk control
"Actions implementing risk management decisions" (ICH Q9)
– Includes risk reduction (if applicable) and risk acceptance
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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
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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
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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.
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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)