Quality Risk Management

1. Quality Risk Management 20th March 2009 - SAPRAA Helena van Schalkwyk Quality Assurance Manager Boehringer Ingelheim, South Africa QRM - SAPRAA 20 March 2009 PTS Dr. R. Beerbohm

2. Agenda • Risk Management - The Essentials • Background of QRM • Structured Risk Management Process: ICH Q9 • Practical Implementation of QRM in your company • Summary and conclusions QRM - SAPRAA 20 March 2009

3. Agenda • Risk Management - The Essentials • Background of QRM • Structured Risk Management Process: ICH Q9 • Practical Implementation of QRM in your company • Summary and conclusions QRM - SAPRAA 20 March 2009

4. Risk Management – The Essentials • Keep Risk Management SIMPLE • Beware of the following pitfalls …… • Recruiting “Risk Management Experts” • Writing a 30 page “Risk Management Policy/SOP”” • Seeing Risk Management as something NEW • The appointment of Risk Management CONSULTANTS QRM - SAPRAA 20 March 2009

5. Risk Management – The Essentials (cont) • We are already managing risks …… • Because we live in a world full of risks! • “Zero Risk” does not exist anywhere! • Risk Management involves: • Identifying risks (what can go wrong/ what are the hazards) • Analysing risks (estimate risks associated with identified hazards) • Evaluating risks (are these risk really that bad?) • Controlling and reducing these risks (mitigate severity, reduce probability of harm, increase likelihood of detection) • Accepting residual risk (accept level of risk) QRM - SAPRAA 20 March 2009

6. Risk Management – The Essentials (cont) • 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 occurrence of harm and severity of harm QRM - SAPRAA 20 March 2009

7. Risk Management – The Essentials (cont) • What is risk? • You only have risk where a hazard exists • Risk is the combination of probability of harm and severity of that harm • Some risks we can’t do anything about • Other risks can be managed • DRIVING to work is a risky business QRM - SAPRAA 20 March 2009

8. Risk Management – The Essentials (cont) • What is your perception of risk? • High, medium or low based on • Probability of occurrence • Severity of potential harm Will you be satisfied with this level of risk or not? QRM - SAPRAA 20 March 2009

9. Risk Management – The Essentials (cont) QRM - SAPRAA 20 March 2009

10. Risk Management – The Essentials (cont) QRM - SAPRAA 20 March 2009

11. Risk Management – The Essentials (cont) • Are you prepared to take your chances and accept the risk? or • Accept that the risk is unacceptable and in need of management and control? QRM - SAPRAA 20 March 2009

12. Risk Management – The Essentials (cont) • Acceptable risk? • Your answer will depend on your • Attitude to risk • Your objective and subjective assessment of information available to you QRM - SAPRAA 20 March 2009

13. Risk Management – The Essentials (cont) • The risks associated with DRIVING in South Africa: • Approximately 14,627 people are killed each year on South African roads (Road Traffic Management Corporation - Road Traffic Report - March 2008 dated 17 April 2008) • That’s 40 people every day • Roads will become even more congested • Cars are becoming both faster and safer Is the risk acceptable to you or not? QRM - SAPRAA 20 March 2009

14. Risk Management – The Essentials (cont) • Risk IDENTIFICATION • What can go wrong? • You may be involved in a fatal road accident – (killing yourself or someone else) • You may be seriously injured and unable to work for a period of time • You may be sent to prison if found guilty of dangerous driving • Incur costs for repairs to damaged vehicles and the inconvenience factor • You driver’s license may be suspended due to (multiple) speeding offences QRM - SAPRAA 20 March 2009

15. Risk Management – The Essentials (cont) • Risk IDENTIFICATION (cont) • What can go wrong? • The inconvenience of relying on public transport (currently very limited availability in SA!) • You may lose your job if you have lost your driver’s license • Social hardships as a result of no income • Higher insurance premiums after the accident claim • High fuel costs resulting from uneconomical driving style QRM - SAPRAA 20 March 2009

16. Risk Management – The Essentials (cont) • DRIVING: Risk ANALYSIS • What is the probability of occurrence? • What are the potential consequences (severity)? • Is this level of risk acceptable … or not? • How can I control (manage) the risks? QRM - SAPRAA 20 March 2009

17. Risk Management – The Essentials (cont) • DRIVING: Risk ANALYSIS (cont) QRM - SAPRAA 20 March 2009

18. Risk Management – The Essentials (cont) • DRIVING: Risk ANALYSIS (cont) QRM - SAPRAA 20 March 2009

19. Risk Management – The Essentials (cont) • DRIVING: Risk ANALYSIS (cont) QRM - SAPRAA 20 March 2009

20. Risk Management – The Essentials (cont) • DRIVING: Risk CONTROL • What actions can you take to • Reduce severity? • Reduce probability of occurrence? • Increase ability to detection? You could • Drive slower • Increase following distance between you and the car in front of you • Buy a car with better safety specifications • Sell your high performance car for a slower/more economical one • Drive at a safer and slower speed • Leave earlier to reach your destination in time QRM - SAPRAA 20 March 2009

21. Risk Management – The Essentials (cont) • DRIVING: Risk CONTROL (cont) • You could • Purchase a “Radar Detector” Please Note: Do NOT use RM to justify what you know is inherently wrong! (Like purchasing a “Radar Detector” system!) • Attend an advanced driving skills course • Talk to those who have witnessed accidents close by • Travel at alternative times (non-peak hours) of the day • Ensure that your car is always in a roadworthy condition QRM - SAPRAA 20 March 2009

22. Risk Management – The Essentials (cont) • DRIVING: Risk REVIEW • Circumstances or situations could change which may then influence your original decision • You may be able to afford a safer car • You may decide to move to a job closer to home that would result in less stressful and dangerous travel • You may witness a serious accident that would influence your driving behaviour/style • New laws may be implemented to lower maximum speed limits, and much tougher enforcement of the traffic laws • You may have children which will motivate you to drive more careful QRM - SAPRAA 20 March 2009

23. Risk Management – The Essentials (cont) • FINALLY….. remember the following: • Never use Risk Management to justify what you know is INHERENTLY wrong • Invest in an advance driving skills course instead of purchasing a “Radar Detector” QRM - SAPRAA 20 March 2009

24. Agenda • Risk Management – The Essentials • Background of QRM • Structured Risk Management Process: ICH Q9 • Practical Implementation of QRM in your company • Summary and conclusions QRM - SAPRAA 20 March 2009

25. Background of QRM • FDA’s CONCERNS – 2001: • Pharmaceutical Manufacturing • Innovation/continuous improvement difficult due to delays in approval at HA’s • Many product formulations and processes derived empirically • Too little knowledge on mechanisms impacting product quality • Very low efficiency and high cost – the opposite of what is necessary in a competitive global market • Industry hesitant/afraid to use new technologies QRM - SAPRAA 20 March 2009

26. Background of QRM (cont) • FDA’s CONCERNS – 2001 (cont): • FDA unable to deliver on their statutory inspection obligations (low budget and high demand) • FDA’s CONCLUSION: • Current approach likely to be inadequate to meet future needs • Need to place emphasis on science and risk-based approaches • FDA’s INITIATIVES since 2002: • Process Analytical Technology (PAT) – not just testing, but a philosophy of Process Understanding • Control in-process rather than end-product testing • Minimises risks of poor quality QRM - SAPRAA 20 March 2009

27. Background of QRM (cont) • FDA’s INITIATIVES since 2002 (cont): • Quality by Design (QbD) approach – which parameters are critical to product quality? • Statistically designed experiments • ICH Q8 QRM - SAPRAA 20 March 2009

28. Background of QRM (cont) • FDA’s INITIATIVES since 2002 (cont): • PARADIGM SHIFT: • Traditional Paradigm Product Variable Starting Materials Variable Processing Parameters Fixed QRM - SAPRAA 20 March 2009

29. Background of QRM (cont) • PARADIGM SHIFT (cont): • QbD paradigm: Starting Materials Variable Processing Parameters Variable Product Fixed QRM - SAPRAA 20 March 2009

30. Background of QRM (cont) • ICH • EU and Japan joined USA to define a new paradigm at an ICH workshop in Brussels in 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 QRM - SAPRAA 20 March 2009

31. Background of QRM (cont) • ICH (cont) • Achieve 5 year vision by incremental steps Pharmaceutical Development (Q8) Old: Data transfer / variable output New: Knowledge transfer / consistent output Quality Risk Management (Q9) Old: Unstructured approach New: Structured process Quality Systems (Q10) Old: Large variability on Q-systems New: Consistency on Q-systems QRM - SAPRAA 20 March 2009

32. Background of QRM (cont) • ICH (cont) Flexible Regulatory Approach • Regulators evaluate risk, based on: • Product and Process Design (Q8) • Measures to evaluate and manage risks (Q9) • Q-system implementation (Q10) • Regulators determine risk and modify level of oversight accordingly for: • Submissions • Post-approval review • GMP Inspections • Result • Removal of barriers to continuous improvement • Efficient use of resources by industry and regulator QRM - SAPRAA 20 March 2009

33. Background of QRM (cont) • Design Space Design space is the multi-dimensional combination and interaction of input variables (e.g. material attributes) and process parameters that have been demonstrated to provide assurance of quality Knowledge Space Design Space Batch process/control parameters The batch process/control parameters are NOT registered and, hence, moving them within the Design Space is NOT a change QRM - SAPRAA 20 March 2009

34. Background of QRM (cont) • ICH Q10 – Pharmaceutical Quality System • Objective of Q10 - to establish a new guideline describing model for an effective QMS for the Pharmaceutical Industry, referred to as the Pharmaceutical QMS QRM - SAPRAA 20 March 2009

35. Background of QRM (cont) • Q10 and Management Responsibility • Management commitment, management review and communication are important • Senior Management • Establish a PQS appropriate for the organisation and compliant with regulations • Ensure that PQS responsibilities and authorities are defined and communicated • Has ultimate responsibility to foster a company-wide commitment to quality and for the successful functioning of the PQS QRM - SAPRAA 20 March 2009

36. Background of QRM (cont) • ICH Q11 – API Development • Q11 will aim to define the development process for API’s similar to those contained in Q8 for medicinal products (Detail for the 3.2.S.2 Section of the CTD) • The New Regulatory Paradigm – Conclusion • It makes sense • FDA is driving it forward • If we can make it to work, it will benefit patients, industry and regulators • We should focus on what adds value for patients QRM - SAPRAA 20 March 2009

37. Background of QRM (cont) • QRM – Summary • Realise that • current situation is not sustainable • By Industry • By Regulators • current situation is not in the best interest for patients QRM is a win: win: win situation for: • Industry • Regulators • and Patients QRM - SAPRAA 20 March 2009

38. Agenda • Risk Management – The Essentials • Background of QRM • Structured Risk Management Process: ICH Q9 • Practical Implementation of QRM in your company • Summary and conclusions QRM - SAPRAA 20 March 2009

39. Structured Risk Management Process: ICH Q9 • Q9 – Table of Contents • Introduction • Scope • Principles of QRM • General QRM Process • RM Methodology • Integration of QRM process into industry and regulatory operations • Glossary • References Annex I – RM Methods and Tools Annex II – Potential Appliances of QRM QRM - SAPRAA 20 March 2009

40. Structured Risk Management Process: ICH Q9 (cont) • Q9 – Principles of QRM Two primary principles: • The evaluation of the quality risk should be based on scientific knowledge and always links back to the protection of the patient. • The level of effort, formality and documentation of the QRM process should be corresponding with the level of risk. QRM - SAPRAA 20 March 2009

41. Structured Risk Management Process: ICH Q9 (cont) • QRM 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 • QRM Process: • Consists of three stages: • Risk Assessment • Risk Control • Risk Review QRM - SAPRAA 20 March 2009

42. Structured Risk Management Process: ICH Q9 (cont) QRM - SAPRAA 20 March 2009

43. Structured Risk Management Process: ICH Q9 (cont) • When a “situation/deviation” occurs • Appoint a “situation/deviation” owner and start to investigate • Seniority dependent on initial severity assessment • Decide what approach to Risk Assessment is applicable • Use a multi-disciplinary team approach • People with the right knowledge and experience for the situation/deviation • Team Leader • At least one person who understands Risk Management tools/methods • FACILITATOR • Determine deadline for completion QRM - SAPRAA 20 March 2009

44. Exampleofprocess mapping ABCD QRM - SAPRAA 20 March 2009

45. Structured Risk Management Process: ICH Q9 (cont) • Deciding on the Risk Management Approach: QRM - SAPRAA 20 March 2009

46. Structured Risk Management Process: ICH Q9 (cont) QRM - SAPRAA 20 March 2009

47. Structured Risk Management Process: ICH Q9 (cont) QRM - SAPRAA 20 March 2009

48. Structured Risk Management Process: ICH Q9 (cont) • Formal tools of Risk Assessment according to ICH Q9, Annex I: QRM - SAPRAA 20 March 2009

49. Structured Risk Management Process: ICH Q9 (cont) • Conclusion: • Using a structured, systematic process for QRM adds value in more complex situations • ICH Q9 provides a good framework for this structured approach • Your company should develop its own implementation approach • Focus to be pro-active QRM - SAPRAA 20 March 2009

50. Agenda • Risk Management – The Essentials • Background to QRM • Structured Risk Management Process: ICH Q9 • Practical Implementation of QRM in your company • Summary and conclusions QRM - SAPRAA 20 March 2009