1. © Safeguarding public health BROMI Variations ·Launch Meeting The Cumberland Hotel, London Anne Ambrose 8 th May 2008

2. Slide 2 May 2008 © BROMI - Variations Variations – High Volume work stream Approx 22,000 variation applications received annually in UK.  50% Type IA  80% National Risk based approach to assessment. Reduction in administrative burden. Predictable approval times Delivery of new ways of working.

3. Slide 3 May 2008 © Current Regulatory Framework Regulation EC 1084/2003 – Mutual Recognition Regulation EC 1085/2003 – Centralised Procedure UK – Follows principles of Regulations EC1084/2003 and EU Best Practice Guidance

4. Slide 4 May 2008 © BROMI Concepts

5. Slide 5 May 2008 © Variations – Proposal for 3-tier model for certain categories of change – Based on MR procedures Self Certification Scientific Validation (IA) 30 Day Assessment (IB) Type IA Type IB Type II

6. Slide 6 May 2008 © BROMI - Variations Choice of Categories for Self Certification or Expedited Processing: Review of National applications determined by MHRA. Categories with low number of invalidation/refusals. Changes that had become Type II with introduction of 1084/2003EC.

7. Slide 7 May 2008 © Variations – 3 tier model Self Certification BROMI – ‘Tell and do’ -Approx 80% of current Type IA; -Approx 7000 per annum in UK Type IA BROMI – 14 day scientific validation Type IB BROMI – 30 day assessment procedure

8. Slide 8 May 2008 © BROMI -Variations How would the 3-tier model help my company? Change in name and address of MA Holder (same legal entity) Current – Type IA with 14 Day validation procedure BROMI – Self Certified change that can be implemented immediately

9. Slide 9 May 2008 © Minor Change in the Manufacture of the Active Ingredient Current – Type IB 30-Day assessment procedure BROMI – Under certain conditions Type IA 14-Day validation Replacement or addition of a manufacturer for a sterile product Current – Type II 90-Day assessment procedure BROMI – Type IB 30-Day assessment procedure

10. Slide 10 May 2008 © BROMI Variations Pilot Initial Phase 1 st February – 31 st July 2007 Limited Number of Companies (11 company groups) Use of Sentinel Portal Audit Evaluation Pilot extended to 31 st January 2008

11. Slide 11 May 2008 © BROMI Variations Pilot – Participating Companies Galpharm GSK Lundbeck Organon Pliva Pfizer Reckitt Benckiser Rosemont Sanofi- Aventis Teva Wockhardt

12. Slide 12 May 2008 © Procedures for Submitting BROMI Notifications Self Certification: Acknowledgment issued as MAH submits application through Sentinel Portal Sentinel/Rama records updated in 14-Days and formal acknowledgment letter issued

13. Slide 13 May 2008 © BROMI Variations Applications Submitted In total 609 BROMI Variations received during the 6 month pilot BROMI Self Certification = 518 BROMI Type IA= 74 BROMI Type IB= 17

14. Slide 14 May 2008 © Applications Submitted

15. Slide 15 May 2008 © BROMI Self Certification

16. Slide 16 May 2008 © Audit Outcome Common Mistakes on applications - Omission of Declaration Form - - Omission of updated PL and/or label - Inadequate QP Declarations - Multiple Ph Eur CEPs in a single notification Most common categories for error - Changes to Tablet or Capsule Markings -Change to Batch Release and QC Arrangements – QP Declarations -Manufacturer of active, – documentation -Change in company name/address

17. Slide 17 May 2008 © BROMI Variations Pilot Company Questionnaire Approval time – great advantage. Admin burden – further reduction required. Guidance and Procedure – further simplification required. Pilot extended to 31 st January 2008

18. Slide 18 May 2008 © Extension of Pilot Categories reviewed – Change #8. Batch release removed. Simplify guidance. Reduce Documentation Requirements. Improved audit

19. Slide 19 May 2008 © Applications Received Feb 07 – Jan 08 Approx 1,500 applications received in total 900 Self-Certified

20. Slide 20 May 2008 © BROMI – Variations Final evaluation of pilot Full Roll-out to MAHs.  National Applications  Portal Applications  Next Steps  Further amendments to Sentinel process and letters issued

21. Slide 21 May 2008 © Next Steps Revision of EU Variation Regulations Two categories of Type IA notification -Those requiring immediate notification -Those that can be included in an annual update Downgrading of variations that have received a scientific opinion

22. Slide 22 May 2008 © Do you have any further suggestions? BROMI@mhra.gsi.gov.uk