The Pharmaceutical Industry and ICH Q9 Peter H Gough Partner, David Begg Associates 1

21st Century GMP Initiative “Seeks to integrate quality systems and risk management approaches into the existing programmes and encourages adoption of modern and innovative manufacturing technology.” “Use existing and emerging science and analysis to ensure that limited resources are best targeted to address important quality issues, especially those associated with predictable or identifiable health risks.” Lester M. Crawford, FDA Deputy Commissioner, 21 August 2002 2

FDA’s “Desired State” Regulatory policies tailored to recognise the level of scientific knowledge supporting applications, process validation and process capability Risk-based scrutiny related to: Level of scientific understanding Capability of process control strategies to prevent or mitigate risk of producing a poor quality product 3

International Conference on Harmonisation (ICH) EU and Japan joined USA to define a new paradigm at an ICH GMP Workshop in Brussels, July 2003 4

ICH – Structure and Members Q uality S afety E fficacy M ultidisciplinary Expert Working Groups (EWGs) 5

ICH GMP Workshop ICH GMP Workshop in Brussels, July 2003 This Workshop agreed a 5 year Vision: Create a single, harmonised global quality standard and interpretation based on good science and risk management principles 6

Incremental Steps to Achieve the Vision The GMP Workshop agreed that the Vision would be achieved by ‘incremental steps’: Q8 EWG, on Pharmaceutical Development, established in September 2003 Q9 EWG, on Quality Risk Management, established in November 2003 Q10 EWG, on Pharmaceutical Quality System, established in November 2005 7

Achieve by Incremental Steps Pharmaceutical Development (Q8) Old: Data transfer / variable output New: Knowledge transfer / Consistent output Changed Paradigm Quality Risk Management (Q9) Old: Unstructured approach New: Opportunity to use a structured process Quality Systems (Q10) Old: Large variability on Q-systems New: Consistency on Q-systems Q8 Q10 Q9 8

Risk Management We all do risk management every day Driving to work Extreme sports Everything in life has some degree of risk Can NEVER have zero risk We all manage risk but we have different risk thresholds 9

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If you do not manage risk; it will manage you. Risk and Management If you do not manage risk; it will manage you. 13

What is Risk Management? PROACTIVELY: Identifying risks (what can go wrong?) Analysing risks Evaluating risks Controlling and reducing these risks Accepting residual risk 14

Pharmaceutical Industry and Risk Management Pharmaceuticals have lagged behind related industries in adopting formal risk management, e.g. Medical devices, ISO 14971 Food, HACCP We are using risk management but historically Implementation was patchy It was often not fully integrated with rest of the Quality System Was performed retrospectively 15

Quality Risk Management Pharmaceutical Quality Risk Management is about: Knowing your processes (manufacturing and business) Identifying what’s truly important Focusing your money, time, energy and people on the things that are really important, i.e. things which have potential to impact patients 16

Advantages of Risk Management Systematic, scientific and data-driven process Reduces subjectivity Ranks risk - allows prioritisation Improves decision making Identifies what gives most benefit to the patient Documented - improves communication 17

Risk Management Must do risk management properly Poor risk management will not impress regulators They will think we do not know what’s really important If everything is critical, nothing is critical Ultimately, it is about credibility Have to begin with the question “What is the impact on the patient?” 18

Why Did We Need ICH Q9 ? Needed ICH Q9 to: Explain what quality risk management is and how it can be applied to pharmaceuticals Provide a common language and an agreed process for the pharmaceutical industry and regulators 19

Why Did We Need ICH Q9? To ensure both industry and regulators have common understanding of Quality Risk Management (QRM) To facilitate moving to the ‘Desired State’ To facilitate communication and transparency To move from ‘fire fighting’ to management of risk 20

ICH Q9 Definitions Harm = damage to health, including the damage that can occur from loss of product quality or availability Hazard = potential source of harm Risk = combination of probability of harm and severity of that harm These are the definitions used in the ICH Q9 Guideline on Quality Risk Management. 21

What Does ICH Q9 Deliver? ICH Q9 provides: The key principles of QRM A common language and process Potential methodologies for QRM Potential applications where QRM can add value 22

ICH Q9 – Principles of Quality Risk Management Two primary principles: 1. The evaluation of the quality risk should be based on scientific knowledge and ultimately link back to the protection of the patient 2. The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk 23

ICH Q9 Quality Risk Management Process Initiate Quality Risk Management Process Risk Assessment Risk Communication Risk Identification Risk Analysis unacceptable Risk Management Tools Risk Evaluation Risk Control Risk Reduction Risk Acceptance Output / Results of the Risk Management Process Risk Review Review Events 24 24

ICH Q9 – Annex 2 Potential Applications for Quality Risk Management To provide a comprehensive evaluation of suppliers and contract manufacturers (e.g., auditing, supplier quality agreements) To provide information for ensuring the availability of pharmaceuticals (e.g., ranking risks to the supply chain) 25

Supply Chain Risks Recent events have exposed several areas of risk: Heparin contamination is USA and elsewhere Melamine contamination of milk in China Further cases of diethylene glycol contamination of glycerol Counterfeit products entering the legitimate supply chain in the EU 26

Supply Chain Risks These supply chain risks are real Probably rank amongst the highest hazards currently faced The must be managed proactively ICH Q9 and this PQG Guide provide an excellent approach 27

PQG Supply Chain Risk Management When we wrote Q9 we hoped it would encourage greater understanding of risk & risk management in the pharmaceutical industry This PQG Guide is exactly the type of detailed thinking that we hoped to see 28

Watch Out ! To add value QRM must be done properly You must have the right experts on your team You must consider all reasonable hazards You must use the right weightings for hazards Ultimately it must be about the patient 29

Watch Out ! FMEA Risk Priority Numbers The absolute number is unimportant RPN allows risks to be ranked Allows action to be prioritised Provides justifiable basis for decision making… including doing nothing! 30

Conclusion We are already doing Quality Risk Management Using a structured, systematic process adds value in many more complex situations Supply Chains are complex! The PQG Guide provides a good framework Use it pro-actively 31

Thank you DBA David Begg Associates www.DBA-global.com 32