1. Building a Cradle-to-Grave Approach with Your Design Documentation and Data Denise D. Dion, EduQuest, Inc. and Gina To, Breathe Technologies, Inc.

2. © 2007 EduQuest, Inc. Agenda The Yin/Yang of Design and CAPA: Cradle to Grave Using Design Transfer to Set Up Your CAPA System Risk Management Transcends Design Case Studies

3. © 2007 EduQuest, Inc. The Yin/Yang of Design and CAPA: Cradle-to-Grave

4. © 2007 EduQuest, Inc. Cradle-to-Grave Concept of Design Design Controls CAPA Product Monitoring Complaints Risk Management Audits Service Reports

5. © 2007 EduQuest, Inc. Design Input

6. © 2007 EduQuest, Inc. Design Inputs - Sources Human Factors Regulations Standards Guidance Preliminary Risk Assessment activities Failure Investigations of Complaints, MDRs, CAPAs, Recalls Marketing and Clinical studies and surveys

7. © 2007 EduQuest, Inc. Requirements to Top-Level Specifications Traceability –Traceability from requirements to specifications to design verification and validation tests and test results is essential for good failure investigations –Traceability should be started during design input and updated as the design progress through remaining phases –Traceability should include Requirements, Specifications and Hazard Mitigations

8. © 2007 EduQuest, Inc. Design Outputs

9. © 2007 EduQuest, Inc. Design Output - 21 CFR 820.30(d) Procedures must … –ensure the identification of outputs essential for proper safety and functioning of the device

10. © 2007 EduQuest, Inc. Essential Outputs Use essential outputs to identify when a Failure Investigation is needed for a given complaint, in- coming, in-process or finished product failure Changes to these should be done with input by design engineers CAPA issues with essential outputs lead to either big improvements to design or process or to introduction of unintended consequences

11. © 2007 EduQuest, Inc. Design Verification/Validation

12. © 2007 EduQuest, Inc. Verification/Validation and CAPA The results of verification and validation tests should be available for use to address issues raised via the CAPA system Traceability from requirements to specifications to verification tests and test results are helpful in identifying true design flaws versus misuse or identification of an unknown failure mode

13. © 2007 EduQuest, Inc. Design Change

14. © 2007 EduQuest, Inc. Design Change Control Changes made to correct or compensate for faults found during any testing should follow the same procedures and controls as for any other change This data should be made readily available for assessing CAPA issues

15. © 2007 EduQuest, Inc. Changes - Tasks Problem identification, evaluation and resolution tracking Proposed change assessment –Does the change affect or may it affect design? Determine impact to appropriate documents (e.g., Requirements, Preliminary Risk Assessment, FMEA, etc.) Documentation update

16. © 2007 EduQuest, Inc. Changes - Tasks Regression analysis or impact assessment and testing to determine change impact to the whole design Testing to evaluate correctness of the implemented change(s) Re-verification and re-validation of the device or device components after changes are implemented

17. © 2007 EduQuest, Inc. Change Control Policy after Design Device Change Control – Assessment of Changes –Changes will be assessed to determine the extent of validation or verification requirements –All changes shall be documented, controlled and where applicable be linked or referenced in the Design History File

18. © 2007 EduQuest, Inc. Design History File

19. © 2007 EduQuest, Inc. Design History File Tells the story of a device or device familys development from beginning to end The DHF contains the documentation necessary to assure changes to design or process for manufacture of the device do not adversely impact the device design and lead to improvement in design and process

20. © 2007 EduQuest, Inc. Design History File Becomes a mixture of living documentation and historical records Living documents for the device family … –Describe the current state of the device –Examples are requirements, specifications, risk, documentation and traceability. –Updated in whole when a change occurs (i.e. new revision)

21. © 2007 EduQuest, Inc. Using Design Transfer to Set Up Your CAPA System

22. © 2007 EduQuest, Inc. Design Transfer Method Transfer Planning Begins Early in the Design Process The Process Must be Designed (or Re-Designed) with the Design of the Device

23. © 2007 EduQuest, Inc. Design Transfer Documents Process FMEA Report Process Design of Experiments Process Validation Protocol Process Validation Test Report

24. © 2007 EduQuest, Inc. Design Transfer Method Process Flow Process Map Production Line Set-Up (with space, equipment and location defined) Process Hazard Analysis Process FMEA –Review and Conformance to Design FMEA

25. © 2007 EduQuest, Inc. Design Transfer: Risk Manufacturability is part of design Process risk needs to include mitigations relative to product risk Product risk documentation is needed to assure process is adequate for design

26. © 2007 EduQuest, Inc. Design Transfer: Essential Elements Product Risk documentation shows what failure modes, components, parts, etc. should be monitored and trended. Identification of essential elements further identifies what needs to be monitored and trended Design and Process Validations indicate critical control points for manufacturing and design

27. © 2007 EduQuest, Inc. Risk Management Transcends Design

28. © 2007 EduQuest, Inc. Risk analysis Intended use and identification of characteristics related to the safety of the medical device Identification of hazards Estimation of the risk(s) for each hazardous situation Risk evaluation Risk control Risk control option analysis Implementation of risk control measure(s) Residual risk evaluation Risk/benefit analysis Risks arising from risk control measures Completeness of risk control Risk assessment Evaluation of overall residual risk acceptability Risk management report Production and post-production information Risk management Risk Process Flow

29. © 2007 EduQuest, Inc. Risk Management: Requirements Preliminary Risk Assessment (top-down risk assessment) should occur while the requirements are being determined. High risk requirements should be modified or not included in the initial requirements document. FMEA or FTA (bottom-up risk assessment) should be used to further refine requirements or determine specifications.

30. © 2007 EduQuest, Inc. Risk Management: Change Changes to design or process need to be assessed against the original risk documents - –Does the change introduce a new failure mode or hazard? –Does the change add a new mitigation to an existing failure mode or hazard? Update the risk documents as appropriate

31. © 2007 EduQuest, Inc. Risk Management: CAPA Trends Trends need to be assessed against the original risk documents - –Does the trend support the original risk determinations for severity, frequency or detectability? –Does the trend show the original risk determinations were either too severe or too generous? Update the risk documents as appropriate

32. © 2007 EduQuest, Inc. Risk Management: Market Surveillance Periodic post-production information review (reference ISO 14971 standard section 9). Need to make a routine practice of reviewing MDRs and adverse events from MAUDE database for problems from competitors like-products New/updated data and risks can be learned from publications, literature reviews, abstracts, presentations, and posters at conferences and congresses

33. © 2007 EduQuest, Inc. Risk Management: Review Allows manufacturers to revisit/review warnings, cautions, contraindications, additional mitigations via labeling, design V&V, production, testing, processes, design. The challenge is to have a practical use of risk management, not just a desk/theoretical exercise to show adherence to ISO 14971 (Standard on Medical Devices – Application of Risk Management to Medical Devices).

34. © 2007 EduQuest, Inc. Case Studies

35. © 2007 EduQuest, Inc. Case Studies Failure modes - found in speaker component used in the devices – were not evaluated as part of new vendor qualification Design input requirements from external standards (ISO vs. ASTM) that are conflicting were not addressed Risk analysis did not include the potential impact of the production environment conditions on the performance of devices

36. © 2007 EduQuest, Inc. Questions???

37. © 2007 EduQuest, Inc. Thank-You