1. Compliance Update Allergenic Products Advisory Committee Meeting March 15, 2002 Teddi Lopez DCM/OCBQ Center for Biologics Evaluation and Research

2. Enforcement Actions Biological Product Deviation Reports –formerly Errors and Accidents Recalls Issues Leading to Enforcement Actions Forward Thinking

3. Enforcement Actions Seizures Injunctions Warning Letters License Suspension License Revocation - NOIR Other –Letter after NOIR –Regulatory Meeting with Agency

4. Enforcement Actions Allergenic Product Manufacturers

5. Inspection vs. Enforcement FY99

6. Inspection vs. Enforcement FY00

7. Inspection vs. Enforcement FY01

8. FY02 Enforcement Actions If inspection in FY01, but action taken in FY02, inspection counted for FY02 Other inspections completed in FY02 pending classification or review –NAI - No Action Indicated –VAI - Voluntary Action Indicated –OAI - Official Action Indicated - warrant further review

9. Inspection vs. Enforcement FY02

10. Biological Product Deviations 21 CFR 600.14 –Final rule effective May 7, 2001 most firms adopting currently –problems with product in distribution Examples - Precipitates, stability failures

11. Biologic Product Deviation Reports

12. Precipitates Accounts for high numbers of BPDs for Allergenic Products Reports may be combined as long as 45 day reporting requirement met Issue discussed between APMA and CBER in October 2000 Interim measures in effect

13. Recalls Voluntary on part of manufacturer Allergenics - related to labeling

14. Allergenic Product Recalls

15. Most Frequent Issues  Enforcement Actions -1999-2002 Inadequate Investigations and Corrective and Preventive Actions –failures during production and testing –complaint handling –precipitates (interim plan) Refiltration/Reprocessing/Reworking –lack of validation –sterility assurance concerns

16. Continued... Container/Closure –integrity –processing Validation –processes, systems, assays –equipment qualification Reserve samples; inspection –211.170

17. Continued…. Biological Product Deviation Reporting –includes stability failures SOPs Deficiencies Annual Review

18. Improvement Noted Container Closure Integrity SOPs –in place; still need tweaking Validation –all areas including refiltration, etc. Annual Reviews and Retention Samples BPDR reporting –but still an issue when precipitates not the cause

19. Forward Thinking Precipitate issue –continue work between manufacturers and CBER with goal of understanding and preventing –may be reported (BPDs) en masse; provided time frame met.

20. Further Information CBER Home Page –www.fda.gov/cber BPD Final Rule –www.fda.gov/cber/biodev/biodev.htm Division of Case Management –301-827-6201