1. What’s New in the FDA’s Pharmaceutical Inspectorate and Risk Based Systems Inspection Rick Perlman Chair Food, Drug, and Cosmetic Division ASQ

2. “Everything that can be invented has been invented” Charles H Duell Commissioner, US Office of Patents urging President McKinley to abolish his office in 1899

3. What is the Pharmaceutical Inspectorate  FDA developed certification program  High level Pharmaceutical Investigators  Primarily used for complex processes or high risk drug products

4. History of the PI  Certification started in 1994  Resulted from Industry asking for a more consistent inspection activity  Will continue as long as needed/funded

5. Purpose  Training and development to maintain qualified staff  Structured approach to obtain, maintain and apply competencies

6. Objective  Assurance that investigators have the skills and knowledge to perform their jobs

7. Certification Areas  Drugs  Blood  Seafood  Medical Devices

8. Types of Drug Certification  Level I  Level II  Level III

9. Certification - Level I  Mandatory  New hire Investigators  Training completed in first 12 months  Demonstrate competency via audit of results

10. Level I Training  Web Based  Classroom –Basic Food and Drug Law –Evidence Development –Investigative Interviewing –Quality Auditing

11. Level I Audit Criteria  Supervisor looks for –General Investigative practices –Evidence Ability to recognize, identify, and collect evidence to support findings –Communication Verbal Written –Professionalism

12. Certification - Level II  Not mandatory  Requirements –Minimum of 25% in Drugs –Submit documentation to Level II Drug Certification Board –Pass performance audit –Recertify every 3 years (18 CEUs)

13. Prerequisites - Level II  Level I Certified  Training –Drug manufacturing and quality control –Pre-Approval Inspections –Industrial Sterilization (Drugs and Devices) –Computer Systems Validation –API manufacturing

14. Certification Board - Level II  National Expert  Experienced Field Investigator  Experts –CDER –CVM  Field Manager  DHRD Specialist

15. Level II Audit Criteria  Compliance Assessment  Evidence  Verbal Communication  Professionalism

16. Certification - Level III  The Pharmaceutical Inspectorate  Not Mandatory  Planning for ~ 50 members by FY 07

17. Level III Eligibility  Minimum 3 years inspecting Drug Firms  Certified as Level II –Must pass six system Audit  Endorsed by District/Office Management  Selected or nominated by Level III Certification Board

18. Level III - How?  Submit request to Supervisor  Submit Certification Packet to Certification Board  Concurrence from District Management  Screened by Certification Board

19. Level III Certification Board  2 Field Investigators (National Experts) operating at Level III  2 Experts –CDER –CVM  DFI program Expert  ORA Field Management  DHRD

20. Level III Candidates  Mainly Investigators with experience and training in pharmaceutical manufacturing  Report directly to ORA District Office  Spend ~80% of time in drug inspection, both Foreign and Domestic

21. Level III - Expected Competencies  Regulating Pharmaceutical Quality in relation to the FDA’s mission  Risk Management  Advanced Quality Systems  Pharmaceutical Science

22. Level III - Expected Competencies  Current Regulatory Programs/Procedures  Technology  Investigations

23. Level III - Admission  Packet successfully reviewed  Pass: –Screening –Training  Participate in Center details  Pass final evaluation

24. Level III - When  First course completed in 2005  Second course 2006

25. Level III - Courses  Quality Systems  Risk Assessment and Management  Critical Thinking  Quality by Design  PAT  Design of Experiments  ICH Guidances  Process Capability  Technology Transfer  CAPA

26. Level III Expectations  Continual learning to enhance their expertise  Develop and implement formal training for –FDA –Industry –State/Local Officials

27. Level III Expectations  Develop/Evaluate in their area of expertise –Programs –Policies –Procedures in their area of expertise  Auditors for Level II or Level III Drug Certification

28. Risk Management  ICH Q9 –Quality Risk Management –Adopted November 9, 2005

29. Risk  Evaluated on –Product, Process, Facility –Controls –Robustness of Quality System

30. Risk  Regulatory Oversight based on –Applications –Post Approval Changes –GMP Inspections

31. Risk - Desired State  Barriers to continuous improvement are removed –manufacturing –product quality  Meaningful Specifications  Common understanding of risk  Industry and Regulators on same page –focused on highest risks –understanding of residual risks

32. Risk - ICH Q9  Provides a guidance document for understanding  Defines common terms  Facilitates –movement toward ‘desired state’ –communication –movement from ‘fire fighting’ to risk management

33. Why ICH Q9  To ensure a common understanding of Quality Risk Management by both industry and regulators

34. What ICH Q9 Provides  A common language and process  Potential methodologies for Quality Risk Management  Where Quality Risk Management can add value

35. What ICH Q9 Provides  Broad risk concepts and principles  Principles for implementation  Elements of the process  Not a single tool but the right tool for the job  Tools

36. What ICH Q9 Is Not  A ‘cookbook’ for risk management  Specifics for your situation  Exhaustive treatment of theory  A list of all potential methods

37. FDA’s Risk Based Inspections  Matrixed Approach  Based on –product type –potential harm –population size

38. Systems Based Inspection  Six Systems –Quality –Materials –Laboratory Controls –Production –Packaging and Labeling –Facilities and Equipment

39. Risk Based Inspection  Depends on potential risk of your product/process  Compliance History  Inspection History  Number of systems –minimum of 2 (always Quality System)

40. Thank You!

41. Questions?