ICH Q9 Quality Risk Management and Introduction to ICH Q10 Pharmaceutical Quality Systems

Emer Cooke Head of Sector, Inspections

The views presented in this presentation are those of the author and should not be understood or quoted as being made on behalf of the EMEA and/or its scientific committees.

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DISCLAIMERS
The views presented in this presentation are those of the author and should not be understood or quoted as being made on behalf of the EMEA and/or its scientific committees. This presentation is based on a standard presentation prepared by some of the ICH Q9 authors. It may include some of these authors views on Quality risk management theory and practice. The presentation does not represent official guidance or policy of authorities or industry.
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Purpose of this part

To guide through the content of the ICH Q9 document Provide some considerations, possible interpretations and where appropriate examples

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Contents of presentation
What is Quality Risk Management (QRM)? Contents of the ICH Q9 guideline Introduction Scope Principles of QRM General QRM Process Risk Management methodology Integration of QRM into industry and regulatory operations Definitions References What makes ICH Q9 different? What ICH Q9 is not intended to do Introduction to Pharmaceutical Quality systems, ICH Q10
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What is Quality Risk Management?

Quality risk management is a systematic process for the assessment,control,communicatio n and review of risks to the quality of the drug (medicinal) product across the product lifecycle. Reference: ICH Q9

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ICH Q9: Quality Risk Management (QRM)

Document is available on the ICH Webpage

www.ich.org

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Table of contents
1. Introduction 2. Scope 3. Principles of Quality Risk Management 4. General Quality Risk Management Process 5. Risk Management Methodology Annex I: Risk Management Methods and Tools 6. Integration of QRM process into Industry and Regulatory operations Annex II: Potential Applications for QRM 7. Definitions 8. References

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1. Introduction
Risk Management Quality Risk Management Quality Systems Harm Severity Stakeholder Product Life Cycle GMP Compliance

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2. Scope
This guideline provides principles & examples of tools of quality risk management that can be applied to different aspects of pharmaceutical quality. These aspects include development, manufacturing, distribution, and the inspection and submission/review processes throughout the lifecycle of drug substances, drug (medicinal) products biological and biotechnological products
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2. Scope
Drug substances (active substance), Drug (medicinal) products, Biological and biotechnological products Including the selection and use of
Raw materials Solvents Excipients Packaging and labelling materials Components
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3. Principles of Quality Risk Management Two primary principles:

The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk

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4. General Quality Risk Management Process

Systematic processes designed to coordinate, facilitate and improve science-based decision making with respect to risk to quality

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Initiate Quality Risk Management Process Risk Assessment

4.
Risk Communication

Risk Identification

Risk Analysis

Risk Evaluation
unacceptable

Risk Management tools

Risk Control Risk Reduction

Risk Acceptance

Team approach

Output / Result of the Quality Risk Management Process Risk Review Review Events

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4. General Quality Risk

Management Process
Decision makers: Person(s) with competence and authority to make a decision Ensuring that ongoing Quality Risk Management processes operate Coordinating quality risk management process across various functions and departments Supporting the team approach
Management responsibility
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What is an acceptable risk?

Risk Control: Risk Acceptance Who has to accept risk? Decision Maker(s) Person(s) with the competence and authority to make appropriate and timely quality risk management decisions Stakeholder Any individual, group or organization that can be affected by a risk Decision makers might also be stakeholders The primary stakeholders are the patient, healthcare professional, regulatory authority, and industry The secondary stakeholders are patient associations, public opinions, politicians
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4. General Quality Risk Management Process

A Risk Acceptance process 1/3
No

Risk reduction step finished Finish baseline for risk acceptance decision
risk identification, risk analysis, risks evaluation, risks reduction

Stakeholders involved as appropiate?

Yes

Revisit risk assessment step

No

All identified risks assessed?

Risk Communication

Initiate Quality Risk Management Process Risk Assessment Risk Identification Risk Analysis Risk Evaluation

unacceptable Risk Control Risk Reduction Risk Acceptance

Risk Management tools

Yes

Output / Result of the Quality Risk Management Process Risk Review Review Events

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4. General Quality Risk Management Process

Measures/ actions needed?
Yes

Evaluate measures
on severity, probability, detectability

Check needed resources

e.g. employee, money

A Risk No Acceptance process 2/3

Measures / Actions appropriate?

Yes

No

Revisit risk reduction step

Other hazards caused?

No

Yes
Initiate Quality Risk Management Process Risk Assessment Risk Identification Risk Analysis Risk Evaluation

Risk Management tools

Risk Communication

unacceptable Risk Control Risk Reduction Risk Acceptance

Is a risk reducible?

Output / Result of the Quality Risk Management Process Risk Review Review Events

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4. General Quality Risk Management Process

A Risk Acceptance process 3/3
Is a risk reducible?
Yes No

Revisit risk assessment step

No

Accept the residual risk?

Yes

Yes

Advantage outweighs risk?

No

Accept risk Sign off documentation

Risk not acceptable Sign off documentation

Ready for communication

Risk Communication

Initiate Quality Risk Management Process Risk Assessment Risk Identification Risk Analysis Risk Evaluation

unacceptable Risk Control Risk Reduction Risk Acceptance

Risk Management tools

Output / Result of the Quality Risk Management Process Risk Review Review Events

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4. General Quality Risk Management Process

Risk Communication
Bi-directional sharing of information about risk and risk management between the decision makers and others Communicate at any stage of the QRM process Communicate and document the output/result of the QRM process appropriately Communication need not be carried out for each and every individual risk acceptance Use existing channels as specified in regulations, guidance and SOPs
Risk Communication

Initiate Quality Risk Management Process Risk Assessment Risk Identification Risk Analysis Risk Evaluation

unacceptable Risk Control Risk Reduction Risk Acceptance

Risk Management tools

Output / Result of the Quality Risk Management Process Risk Review Review Events

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4. General Quality Risk Management Process Risk Communication

Exchange or sharing of information, as appropriate Sometimes formal sometimes informal Improve ways of thinking and communicating
Initiate Quality Risk Management Process Risk Assessment Risk Identification Risk Analysis Risk Evaluation Risk Management tools Risk Communication unacceptable Risk Control Risk Reduction Risk Acceptance

Increase transparency

Output / Result of the Quality Risk Management Process Risk Review Review Events

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CONSIDERATIONS

Quality risk management Communication

facilitates trust and understanding

Regulators operation
- Reviews - Inspections

Industry operation
- Submissions - Manufacturing

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4. General Quality Risk Management Process

Risk review: Review Events Review the output / results of the QRM process Take into account new knowledge and experience Utilise for planned or unplanned events Implement a mechanism to review or monitor events Reconsideration of risk acceptance decisions, as appropriate
Risk Communication Initiate Quality Risk Management Process Risk Assessment Risk Identification Risk Analysis Risk Evaluation

unacceptable Risk Control Risk Reduction Risk Acceptance

Risk Management tools

Output / Result of the Quality Risk Management Process Risk Review Review Events

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5. Risk Management Methodology

One method all inclusive?

Initiate Quality Risk Management Process Risk Assessment Risk Identification Risk Analysis Risk Evaluation Risk Management tools Risk Communication unacceptable Risk Control Risk Reduction Risk Acceptance

Output / Result of the Quality Risk Management Process Risk Review

Cartoon: Zurich Insurance Inc.

Review Events

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Expectations on methods and tools

Supports science-based decisions A great variety are listed but other existing or new ones might also be used No single tool is appropriate for all cases Specific risks do not always require the same tool Using a tool the level of detail of an investigation will vary according to the risk from case to case Different companies, consultancies and competent authorities may promote use of different tools based on their culture and experiences
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Contributing items to manage quality risks

System Risk (facility & people) e.g. interfaces, operators risk, environment, components such as equipment, IT, design elements System Risk (organisation) e.g. Quality systems, controls, measurements, documentation, regulatory compliance Process Risk e.g. process operations and quality parameters Product Risk (safety & efficacy) e.g. quality attributes: measured data according to specifications
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5. Risk Management Methodology

Supports a scientific and practical approach to decision-making Accomplishing steps of the QRM process Provides documented, transparent and reproducible methods Assessing current knowledge Assessing probability, severity and sometimes detectability
Risk Communication

Initiate Quality Risk Management Process Risk Assessment Risk Identification Risk Analysis Risk Evaluation

unacceptable Risk Control Risk Reduction Risk Acceptance

Risk Management tools

Output / Result of the Quality Risk Management Process Risk Review Review Events

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5. Risk Management Methodology

Adapt the tools for use in specific areas Combined use of tools may provide flexibility The degree of rigor and formality of QRM Should be commensurate with the complexity and / or criticality of the issue to be addressed and reflect available knowledge Informal ways empirical methods and / or internal procedures
Initiate Quality Risk Management Process Risk Assessment Risk Identification Risk Analysis Risk Evaluation

Risk Management tools

Risk Communication

unacceptable Risk Control Risk Reduction Risk Acceptance

Output / Result of the Quality Risk Management Process Risk Review Review Events

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Annex I: Risk Management Methods and Tools

Provides a general overview of and references for some of the primary tools Might be used in QRM by industry and regulators This is not an exhaustive list No one tool or set of tools is applicable to every situation in which a QRM procedure is used For each of the tools Short description & reference Strength and weaknesses Purely illustrative examples

Initiate Quality Risk Management Process Risk Assessment Risk Identification Risk Analysis Risk Evaluation

Risk Management tools

Risk Communication

unacceptable Risk Control Risk Reduction Risk Acceptance

Output / Result of the Quality Risk Management Process Risk Review Review Events

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Overview: Some tools and their key words

Failure Mode Effects Analysis (FMEA) Break down large complex processes into manageable steps Failure Mode, Effects and Criticality Analysis (FMECA) FMEA & links severity, probability & detectability to criticality Fault Tree Analysis (FTA) Tree of failure modes combinations with logical operators Hazard Analysis and Critical Control Points (HACCP) Systematic, proactive, and preventive method on criticality Hazard Operability Analysis (HAZOP) Brainstorming technique Preliminary Hazard Analysis (PHA) Possibilities that the risk event happens Risk ranking and filtering Compare and prioritize risks with factors for each risk
Initiate Quality Risk Management Process Risk Assessment Risk Identification Risk Analysis Risk Communication Risk Evaluation unacceptable Risk Management tools Risk Control Risk Reduction Risk Acceptance Output / Result of the Quality Risk Management Process Risk Review Review Events

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5. Risk Management Methodology

Supporting statistical tools Acceptance Control Charts (see ISO 7966) Control Charts (for example) Control Charts with Arithmetic Average and Warning Limits (see ISO 7873) Cumulative Sum Charts; CuSum (see ISO 7871) Shewhart Control Charts (see ISO 8258) Weighted Moving Average Design of Experiments (DOE) Pareto Charts Process Capability Analysis Histograms Use others that you are familiar with.
Risk Assessment Risk Analysis Risk Communication Risk Evaluation Risk Control Risk Reduction Risk Review Review Events

Initiate Quality Risk Management Process

Risk Identification

unacceptable

Risk Management tools

Risk Acceptance

Output / Result of the Quality Risk Management Process

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6. Integration into Industry and Regulatory Operations

Foundation for science-based decisions Does not obviate industrys obligation to comply with regulatory requirements May affect the extent and level of direct regulatory oversight Degree of rigor and formality commensurate with the complexity and/or criticality of the issue Implement QRM principles when updating existing guidelines
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Annex II: Potential Applications for QRM

This Annex is intended to identify potential uses of quality risk management principles and tools by industry and regulators. However, the selection of particular risk management tools is completely dependent upon specific facts and circumstances. These examples are provided for illustrative purposes and only suggest potential uses of quality risk management. This Annex is not intended to create any new expectations beyond the current regulatory requirements. ICH Q9 Introduction to Annex II

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Annex II: Potential Applications for QRM

Quality risk management as part of Integrated quality management Documentation Training and education Quality defects Auditing / Inspection Periodic review Change management / change control Continual improvement
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Competent authorities Industry

Annex II: Potential opportunities for conducting quality risk management

Quality risk management as part of Regulatory operations Inspection and assessment activities Industry operations Development Facilities, equipment and utilities Materials management Production Laboratory control and stability testing Packaging and labelling
Competent authorities

Industry
Competent authorities

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What makes Q9 different to other Quality guidelines?

It provides principles and a framework for decision making > Q9 is a quality improvement methodology It is a guidance not an SOP > Simple > Flexible > Not mandatory It supports science-based decision making > Facilitates communication and transparency > Supports build up trust Q9 is for both industry and competent authorities (CA)
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What does Q9 NOT do?

Q9 does not remove regulatory requirements Does not shift decision making from company to regulatory authority

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Introduction to Pharmaceutical Quality Systems Q10

Objective: To establish a new tripartite guideline describing a model for an effective quality system needed to establish and maintain a state of control that can ensure the realisation of a quality drug product and facilitate continual improvements over the product lifecycle Complements existing GMPs Aligned with ISO concepts Paradigm shift from discrete GMP compliance to comprehensive quality systems approach Promotes continual improvement through process understanding and risk management
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Introduction to Pharmaceutical Quality Systems Q10

Contents: Introduction Pharmaceutical Quality System design considerations product realisation Continual improvement QRM Management responsibility Continual improvement Continual improvement over product lifecycle
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Additional reading
http://www.ich.org/cache/html/3158272-1.html

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