1. The FDA Regulatory and Compliance Symposium Preparing for the FDA’s Risk-Based Inspections Presented By: Martin Browning, EduQuest, Inc. www.EduQuest.Net

2. © 2005 EduQuest, Inc. Preparing for the FDA’s Risk-Based Inspections – Agenda A little history Current driving forces FDA “risk” initiatives Inspectional process changes Preparation

3. © 2005 EduQuest, Inc. Risk and FDA Response to catastrophe (or perceived catastrophe) Patients and users Influence of the Medical Device cGMP regulation Product risk Process risk Influence of harmonization issues

4. © 2005 EduQuest, Inc. Risk and FDA Safety Net –Gatekeeper –Inspections –Self reporting Risk-benefit –Time-to-market and availability to patients –Post-market studies

5. © 2005 EduQuest, Inc. Risk and FDA Loss of the little “c” (e.g. cGMP) –Scope growth (Foods and Drugs to Foods, Drugs, Cosmetics, Devices, Biological Products, Radiation Emitting Products, Terrorism,…) –Technology explosion (Computer and Software driven) –Lack of competitiveness in hiring and loss of competitiveness in retaining –Rigidity –Response of the regulated industries

6. © 2005 EduQuest, Inc. Current Driving Forces Medical mistakes Food/Drug/Supplement/etc. interactions The Generic Drug Scandal Criticisms of approvals “Partnering with Industry” Pharmaceutical promotion

7. © 2005 EduQuest, Inc. Current Driving Forces FDA funding by “User Fees” Prescription drug costs in the US FDA stance on “re-importation” The politicizing of the FDA Incredibly low Agency Funding Low Agency morale

8. © 2005 EduQuest, Inc. The Agency Response Do more with less and less –Resulted in doing less with less Rebuild the “Science Base” of the Agency –Increased use of “outside” scientists Turn to technology –Pray for Process Analytic Technology Focus resources on “risk”

9. © 2005 EduQuest, Inc. FDA “Risk” Initiatives Internal Initiatives –Focus on internal systems –Schedule inspections based on risk Premarket Initiatives –More meaningful data –More automation in submissions –More electronic analysis –Speedier approvals

10. © 2005 EduQuest, Inc. FDA “Risk” Initiatives Other Initiatives –“Science” based approaches –PAT (Process Analytic Technology) –Reinterpretation of Part 11 –Centralizing Warning Letter Review –Inspectional process changes –Etc.

11. © 2005 EduQuest, Inc. Inspectional Process Changes Choosing whom to inspect The Investigator Smoothing of the reporting process Focus of the inspection Increased dangers

12. © 2005 EduQuest, Inc. Preparing for the FDA’s Risk-Based Inspections Some of you should prepare for more frequent inspections based upon –Complaints, AERs, MDRs –Known product complexity –Known manufacturing process complexity –Life sustaining/supporting status –Inspectional history (recalls, 483s, Warning Letters, etc.) Improve your “score” on FDA’s “rating system”

13. © 2005 EduQuest, Inc. Preparing for the FDA’s Risk-Based Inspections The Investigator –“Pharmaceutical Inspectorate” (Team Biologics, National Experts, etc.) –Increased use of District or Regional inspection teams –Increased specialization Smoothing of the reporting process –“Turbo – 483”, “Turbo – EIR” (revisions, I hope) –Slightly improved data systems

14. © 2005 EduQuest, Inc. Preparing for the FDA’s Risk-Based Inspections Focus on “Systems” –FDA believes “Quality Systems” map clearly to all cGMP regulations – understand how the “map” applies to you –Keep up with FDA guidance, compliance programs, legal actions, and monitor Agency presentations –Understand the “QSIT” model, and the regulatory approach used in the Medical Device cGMPs

15. © 2005 EduQuest, Inc.

16. Preparing for the FDA’s Risk-Based Inspections Focus on “Systems” –Have a quality system and all subsystems, document them, use them, and have evidence of their use –Prepare for “bottom-up” inspections beginning with complaints, OOS results, failure investigations, AERs, MDRs, non-conformances, process deviations, etc. The causes of these events should be included in (or be added to) your established patient, product, and process risks

17. © 2005 EduQuest, Inc. Preparing for the FDA’s Risk-Based Inspections Focus on “Systems” –Pay special attention to the “Management Controls” subsystem and its effectiveness –FDA expects quality control, quality assurance, and quality oversight processes – assure that these processes work and their effectiveness is communicated to “management with executive responsibility”

18. © 2005 EduQuest, Inc. Preparing for the FDA’s Risk-Based Inspections Focus on “Risk” –Patient Risk –Product Risk –Process Risk –Have formal methodologies for risk management appropriate for your products (e.g. FMEA, FMECA, FTA, HACCP)

19. © 2005 EduQuest, Inc. Preparing for the FDA’s Risk-Based Inspections Focus on “Risk” –Map and understand your processes identifying specifications, control points, critical control points, process monitoring, and risk mitigations –Build new processes based on science –Rebuild existing processes –Validate processes, treating validation as a life-cycle process

20. © 2005 EduQuest, Inc. Preparing for the FDA’s Risk-Based Inspections Increased Dangers –Fewer “bites-at-the-apple” –More centralized FDA coordination/communication –“Bottom-up” approaches can lead to erroneous conclusions –Some will look at FDA’s initiatives as excuses not to comply with regulations – this would be a critical mistake