Goals and Priorities ORA and Denver District

1. Goals and PrioritiesORA and Denver District LaTonya M. Mitchell Denver District Director Southwest Regional Office Office of Regulatory Affairs Office of Global Regulatory Operations & Policy

4. Commissioner’s Priorities for ORA • Globalization & Partnerships • Recommendations in “Pathway to Global Product Safety & Quality” Report • National Integrated Food Safety System; FSMA Mandates • Infrastructure • Science • Laboratory • IT • Operational Efficiency & Productivity • Inspections • Recalls • Emergency Response • Office of Criminal Investigations

5. ORA FY13 Priorities Efficiency/Productivity Improvements • Emergency Response • CORE Network • Recalls • Inspection • Conduct • Report Writing • Evidence Documentation • Abbreviated Reporting • Enforcement • Timeliness of W/L close outs/reinspection of non-compliant firms (OAI) • Streamlining seizure & injunction actions • Miscellaneous Business Process Improvements • QMS

6. ORA FY13 Priorities Inspectional/Enforcement Productivity & Resources Study • "Efficiency" Initiative – Five Projects • Eliminate/reduce the collection of documentation for interstate commerce • Implementation of component inspections for foods • Institutionalize two system inspections for drugs • Outsource recall audit checks • Expand use of hand helds for inspections

7. ORA Changes: DEN-DO

8. DEN-DO Staff Growth

9. Investigations Staffing 5 Supervisory Groups • 44 CSO’s on board • 3 vacancies to meet TO • Primary Program Areas • Devices 7 • Biologics/Tissue 8 • Pharmaceutical 4 • Food/Feed 25 • Most CSO’s are not 100% dedicated to a commodity

10. Science Branch Staffing • 3 Microbiology and 3 Chemistry Supervisory Groups • Also house Animal Drug Research Center • 52 Analysts on board • 2 vacancies to meet TO • Specialties: • Microbiologists: 27 • Chemists: 25

11. Denver District Priorities • Workplan and Performance Goals • Working with State Counterparts • Laboratory • Quality Management System • Enforcement

12. Howard ManresaCompliance Branch Director Compliance Trends in the Medical Device Industry

13. DEN-DO Enforcement Actions FY 2011 21 Warning Letters (9 Med Device, 6 drug) 5 Untitled Letters (4 Med Device) 21 Regulatory Meetings 110 Denver District Initiated Recalls 122 FOIA Requests

14. DEN-DO Enforcement Actions FY 2012 1 (FY13) Suspension of Registration Order 18 Warning Letters (1 Med Device, 6 Drug) 6 Untitled Letters (3 Med Device, 1 Drug) 12 Regulatory Meetings 152 Denver District Initiated Recalls 111 FOIA Requests

15. Top 10 Medical Device Citations in 2012

16. 2012 • 820.100(a) – Corrective and Preventive Action Procedures • 820.198(a) – Complaint procedures • 803.17 – Written MDR procedures • 820.100(b) – Corrective and Preventive Action (Documentation) • 820.50 – Purchasing Procedures

17. 2012 • 820.75(a) – Inadequate Validation (process) • 820.90(a) – Procedures for control of “out of spec” product • 820.30(i) – Design Change Procedures • 820.198(c) – Complaint Handling • 820.181 – Device Master Record

19. TOP TWO FDA 483 CITATIONS FOR MEDICAL DEVICE FIRMS Number One • Inadequate corrective and preventive actions procedures (CAPA) – 21 CFR 820.100(a). • For example: • Failure to analyze processes, service records, quality audit reports, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming product; • Cause of nonconformities relating to product, processes and the quality system are not investigated; • Actions needed to correct and prevent recurrence of nonconforming product or other quality problems are not identified;

20. TOP TWO FDA 483 CITATIONS FOR MEDICAL DEVICE FIRMS Number Two • Inadequate complaint handling procedures – 21 CFR 820.198(a). • For example: • Complaints are not processed in a uniform or timely manner; • are not documented; or • have not been evaluated for MDR applicability.

21. Review of Post-Inspection Responses • FDA will allow firms 15 business days after the FDA 483 was issued, to provide a response • If received within 15 business days, • FDA will perform a detailed review of the response before determining whether to issue a warning letter. • Any warning letter issued will recognize receipt of the response and the adequacy of the firm’s corrective actions. Reference: Federal Register, Vol. 74, No. 153 dated August 11, 2009, effective September 15, 2009.

22. Review of Post-Inspection Responses, cont. • Ongoing or promised corrective actions generally will not preclude the issuance of a warning letter. • Responses received after 15 business days will be evaluated separately from the warning letter

23. Warning Letter Close Out • If FDA determines that a firm has adequately corrected Warning Letter violations, FDA will send a close-out letter.  • Applies to Warning Letters issued after September 1, 2009. • FDA will indicate close-out on its website: • http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm

24. Working More Closely with Regulatory Partners E. Mark HarrisDirector, Investigation Branch

25. Performance Metrics

26. Performance Metrics

28. Key Achievements GDUFA advances critical values Timely access to generic drugs Safe, high-quality generic drugs Maintains affordability of generic drugs Increases transparency Addresses globalization Advances regulatory science Is expected to put FDA’s generic drug program on a stable financial footing

29. Generics Success = Regulatory Challenge $1.07 trillion in savings (2002-2011) has resulted in continued success and growth Program funding has remained relatively flat Generics industry success has come to represent an unprecedented regulatory challenge in terms of Size Scope Geography

30. GDUFA Addresses Those Challenges $299 million per year Ten-month review cycle for 90% in year 5 Effectively eliminate the backlog within 5 years Risk-adjusted, biennial inspections parity of foreign and domestic frequency in year 5 Efficiency enhancements, starting day one, are a critical component of GDUFA 4 types of fees: backlog; DMF; ANDA/PAS; Facility 70% of program revenue from facilities; 30% from applications 80% of program revenue from FDF; 20% from API

31. FDA Commitments: ANDAs Abbreviated New Drug Applications (ANDAs) Complete response letters Division-level deficiency review Prompt communication of easily correctable deficiencies First cycle meetings For years 1 and 2 of the program, expedite paragraph IV (Day 1 Submissions)

32. Selected FDA Commitments: DMFs and Inspections Drug Master Files (DMFs) Initial completeness assessment ‘Available for reference’ list on the web DMF completeness letter Inspections Release inspection classification and date Third-party foreign regulator inspection program evaluation

33. GDUFA Outline Application fees Applications in the backlog (year 1 only) Drug master file fee (and availability for reference list) ANDA and prior approval supplement (PAS) filing fee Facility fees Involved in manufacture of generic drugs, whether active pharmaceutical ingredient (API) or finished dosage form (FDF); domestic or foreign Individual fees calculated/published upon implementation Fees not linked to types of services; rather overall goals

34. GDUFA Outline (continued) Identification of facilities Effect of failure to pay fees Other provisions Appropriations and spending triggers Streamlined hiring authority Definitions Exemption for positron emission tomography (PET) drugs Reauthorization

35. GDUFA: Important Dates and Deadlines User Fees: Incurred beginning on October 1, 2012 Payment amounts: Backlog Fee (published) Applications Fees – DMF, ANDA, PAS (published) Facility Fees (to publish by mid-Jan. 2013) Business entities must submit information online and generate an invoice. No bills will be sent. Facility Self-Identification: Notice of Requirement (published) Once published, facilities have 60 days to self-identify Self-ID is distinct from drug registration and listing requirement

37. Working more closely with regulatory partners • Expand the Health Canada Multipurpose Audit Program - Pilot Phase operational phase • Determine one format for audit reports such that only one audit report would serve both Health Canada and FDA. • FDA to work with or accompany Health Canada on surveillance audits on third party auditing groups in the program.

38. Questions?