Lessons Learned in Integrating Risk Management and Process Validation

1. Lessons Learned in Integrating Risk Management and Process Validation Medical Device Congress Harvard – March 2007 Jim Handzo – Senior Manager QA Innovative Spinal Technologies Fran Akelewicz – Principal Practical Solutions

2. Agenda • Optimizing the validation activities sequence using risk management • Determining the statistical approach and acceptance criteria based on risk • Maximizing test plans and resources

3. Approach • For illustration purposes we will use an example of: • Safety product (functional approach) New feature -a collar with a hinged rectangular plastic guard which will clip over the needle after use to prevent the user from getting stuck with the needle

4. Optimizing the validation activities sequence

5. Key questions for process validation • What are the important design characteristics? • Where and how are they impacted in the process? • What resources do I need? • What do I do first? • How should I conduct the validation? • What do I do if I don’t like the answer?

6. What are the important design characteristics? • Product inputs to process validation • Key design features • Residual risk profile (dFMEA) • Controls for the risk-prioritized design features

7. What are the important design characteristics? • Product Inputs (User and Patient) • Key Design Features • Tools • Customer Requirements Matrix • Design Requirements Matrix

8. What are the important design characteristics? • Product Inputs (User and Patient) • Customer Requirements Matrix • Focused on user needs • Focused on business needs

9. What are the important design characteristics? • Product Inputs (User and Patient) • Design Requirements Matrix • Focused on risk analysis

10. What are the important design characteristics? • Product residual risk profile • Without safety feature X

11. What are the important design characteristics? • Product residual risk profile • With safety feature X

12. Where and how are key design features impacted in the process? • Process Inputs • Determine process control points that potentially impact the design features • Are process control points • One to one? • One to many? • Many to one? • Determine residual risk impact (pFMEA, FTA, etc.)

13. Where and how are key design features impacted in the process? • Determine various process points that potentially impact the design feature

14. Where and how are key design features impacted in the process? • Determine if the control points are • One process point to one design feature • One process point to many design features • Many process points to one design feature

15. Where and how are key design features impacted in the process? • Use tools to characterize process outputs vs. design features • Design of Experiments (DOE) • Edge of Failure (EOF) Studies • Ranging Studies • Mean Time between Failures (MTBF) • Cpk vs. Ppk • Determine process residual risk • Process Map & pFMEA • FTA • Waterfall with Feedback Loop • EN 60601-1-4 PEMS “V” Diagram

16. Where and how are key design features impacted in the process? • Process residual risk profile • Changes probability, not severity X

17. What resources do I need? • Dependent on type of product and/or process being evaluated • Electrical Engineer • Software Engineer • Reliability Engineer • Quality Engineer • Commensurate with the degree of residual risk

18. What do I do first? • Develop Process Validation Priority Risk Chart • Similar methodology to Product Risk Chart • Process effects on product are rated based on their impact • Safety • Performance • Acceptance • Compliance • Verification • Can also be used to develop a company Validation Master Plan

19. Process Map • Formation and attachment of needle guard with collar attachment

20. What do I do first? • Process Validation Priority Risk Chart

21. What do I do first • Apply to • Entire processes • Sub-processes (then add)

22. Where should validation testing occur?

23. What do I do if I don’t like the answer? • Have a “Plan B” • Identify assignable causes • Justify discounting results with great care • Revisit assumptions made during validation setup • Revisit probabilities assigned to key design features • But you cannot change severity unless you change the design • Define contingencies in acceptance criteria

24. Determining the statistical approach and acceptance criteria based on risk

25. Determining acceptance criteria • Document in company policy • Similar to product risk chart • Key elements derived from product risk chart • Severity drives confidence levels • Confidence levels and probability drive sampling plans • Qualitative probabilities (Frequent, Probable, etc.) must be expressed quantitatively • Sampling plans should be discriminating enough to detect defects that relate to high severity/frequently occurring hazards

26. Determining acceptance criteria • Acceptance Criteria Risk Chart

27. Sampling plan determination • Determine the operating characteristic (OC) curve of selected sampling plan • Incorporate quantitative probabilities • Determine acceptable errors • Type I (Producer’s Risk) – we say it’s bad when it’s not • Type II (Consumer Risk) – we say it’s good when it’s not • Does it match residual risk and probability?

28. Sampling plan determination • Determine how much risk (error) you can tolerate in your estimates • Attributes • Percent defective error tolerance • Variables • Error tolerance of the average • Must constantly weigh sample size vs. estimate risk (error) • Economics vs. certainty

29. Sampling plan determination

30. Sampling plan determination • Use appropriate probability distributions when determining sampling plans • Binomial • Large populations • Sampling with replacement • Hypergeometric • Small populations • Sampling without replacement

31. Sampling plan determination

32. Sampling plan determination

33. Sampling plan determination • Sampling Calculators available for download at: www.devicecongress.com/agenda/day2.html (Once on the website, go to Track A, 4:10pm session, for links to presentation materials. Calculators are in the excel document.)

34. Maximizing test plans and resources

35. Maximizing Test Plans and Resources • Identify resources based on risk • Prioritize the process validation activities based on risk • Choose the acceptance criteria • Choose the appropriate sample methodology to minimize the business risk

36. Change Control • Once process validation is completed you have established a “state of control” • Any changes made should consider: • Impact to product design risk (design verification testing; design validation testing) • Impact to process design risk (equipment design decisions) • Impact to control of risk within process

37. Conclusions • Risk management in process validation: • Provides the opportunity to: • challenge existing assumptions • “think out of the box” • Acknowledges the risks that we have taken (product and business) • Provides a common language • Provides a framework for consistency • Formalizes what we have done • Contributes to safer products

38. Questions

39. Thank You ! Jim Handzo Innovative Spinal Technologies +1 508 452-3517 jhandzo@istspine.com www.istspine.com Fran Akelewicz Practical Solutions +1 215 337-9238 franakelewicz@comcast.net www.practicalsolns.net