Quality Risk Managemment ICH Q9

ICH Guidelines on Risk Management,Methods & Tools

1. ICH Guidelines on Risk A ssessment & Risk M anagement M ethods & Tools Presented by: Kiran Singh M .Pharm ( Pharmaceutical quality assurance) 2 nd semester

2. Basic terms Harm :-Damage to health, including the damage that can occur from loss of product quality or availability. Hazard : – The potential source of harm (ISO/IEC Guide 51). Risk : – The combination of the probability of occurrence of harm and the severity of that harm (ISO/IEC Guide 51). Severity : – A measure of the possible consequences of a hazard. Detectability: – The ability to discover or determine the existence, presence, or fact of a hazard.

3. Quality : – The degree to which a set of inherent properties of a product, system or process fulfills requirements (see ICH Q6A definition specifically for "quality" of drug substance and drug (medicinal) products.) Quality Risk Management : – A systematic systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle. Quality System : – The sum of all aspects of a system that implements quality policy and ensures that quality objectives are met. R isk 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.

4. 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.

5. PRINCIPLES OF QUALITY RISK MANAGEMENT Two primary principles of quality risk management are:

6. GENERAL QUALITY RISK MANAGEMENT PROCESS Quality risk management is a systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle. Systematic processes designed to coordinate, facilitate and improve science-based decision making with respect to risk to quality Figure 1: Overview of a typical quality risk management process :

7. 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

8. Risk assessment Risk identification What might go wrong? Risk analysis What is the likelihood (probability) it will go wrong? Risk evaluation What are the consequences (severity)?

9. Risk Assessment: Risk Identification Risk identification is a systematic use of information to identify hazards referring to the risk question or problem description . Information can include : – historical data – theoretical analysis – informed opinions – concerns of stakeholders

10. Risk Assessment: Risk Analysis Risk analysis is the estimation of the risk associated with the identified hazards . It is the qualitative or quantitative process of linking the likelihood of occurrence and severity of harms . In some risk management tools, the ability to detect the harm (detectability) also factors in the estimation of risk.

11. Risk Assessment : Risk analysis Maintain a robust data set! Start with the more extensive data set and reduce it Trend and use statistics (e.g. extrapolation) Comparing between different sets requires compatible data Data must be reliable Data must be accessible

12. Risk Assessment: Risk Evaluation Compare the identified and analysed risk against given risk criteria Consider the strength of evidence Risk score for all three of the fundamental questions – What might go wrong? – What is the likelihood (probability) it will go wrong? – What are the consequences (severity)?

13. Risk control Risk control includes decision making to reduce and/or accept risks. The purpose of risk control is to reduce the risk to an acceptable level . Risk control might focus on the following questions: - Is the risk above an acceptable level? - What can be done to reduce or eliminate risks? - What is the appropriate balance among benefits, risks and resources? - Are new risks introduced as a result of the identified risks being controlled?

14. Risk Control: Risk Reduction Mitigation or avoidance of quality risk when it exceeds acceptable level Elimination of risks, where appropriate Focus actions on severity and/or probability & detectability of harm It might be appropriate to revisit the risk assessment during the life cycle for new risks or increased significance of existing risks

15. Risk acceptance Risk acceptance is a decision to accept risk. F ormal decision to accept the residual risk or it can be a passive decision in which residual risks are not specified. May require support by (senior) management Applies to both industry and competent authorities Discuss the appropriate balance between benefits , risks, and resources Risk acceptance is not – Inappropriately interpreting data and information – Hiding risks from management /competent authorities

16. 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

17. 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 • Exchange or sharing of information, Use existing channels as specified in regulations , guidance and SOP’s • Sometimes formal sometimes informal – Improve ways of thinking and communicating • Increase transparency

18. Risk review: Review Events Review the output / results of the QRM process Take into account new knowledge and experience Utilize for planned or unplanned events Implement a mechanism to review or monitor events Reconsideration of risk acceptance decisions,as appropriate

19. Overview: Some tools and their key words Failure Mode Effects Analysis (FMEA ) – Break down large complex processes into manageable steps ( FMEA can be used to prioritize risks and monitor the effectiveness of risk control activities ) Failure Mode, Effects and Criticality Analysis (FMECA) – FMEA & links severity, probability & detectability to criticality ( FMECA application in the pharmaceutical industry should mostly be utilized for failures and risks associated with manufacturing processes ) Fault Tree Analysis (FTA) – Tree of failure modes combinations with logical operators (FTA can be used to establish the pathway to the root cause of the failure. FTA can be used to investigate complaints or deviations in order to fully understand their root cause )

20. Hazard Analysis and Critical Control Points (HACCP) – Systematic, proactive, and preventive method on criticality (HACCP might be used to identify and manage risks associated with physical, chemical and biological hazards ) Hazard Operability Analysis (HAZOP) – Brainstorming technique (HAZOP can be applied to manufacturing processes, including outsourced production and formulation as well as the upstream suppliers, equipment and facilities for drug substances and drug (medicinal) products)

21. Preliminary Hazard Analysis (PHA) – Possibilities that the risk event happens (PHA is most commonly used early in the development of a project when there is little information on design details or operating procedures ) Risk ranking and filtering – Compare and prioritize risks with factors for each risk (Risk ranking and filtering can be used to prioritize manufacturing sites for inspection/audit by regulators or industry )

22. THANK YOU….!!!!!