6 th Annual Science and Standards Symposium January 16, 2013 Istanbul US Regulatory Updates

1. 6th Annual Science and Standards SymposiumJanuary 16, 2013IstanbulUS Regulatory Updates Roger L. Williams, M.D. CEO and Chair, Council of Experts

2. The Washington, D.C. Area: USP and FDA

3. Food and Drug Administration, White Oak Campus

4. USP Homes

5. Food and Drug Administration

7. The Latest • Generics ‘Super’ Office • Office of Generic Drugs • Matches Office of New Drugs • Director: Dr. Greg Geba • Office of Product Quality • Brings in new drug chemists (Office of New Drug Product Quality/ONDPQ) • Brings in generic drug chemists • Brings in Office of Manufacturing and Product Quality (formerly with Office of Compliance) • Review of CMC for new drugs, generic drugs and post-approval changes, together with inspection component

8. FDASIA (Food and Drug Administration Safety and Innovation Act) • Signed into law July 2012 • Reauthorizes for five years user fee programs for prescription drugs and medical devices • Establishes new user fee programs for generic drugs (GDUFA) and biosimilars • Makes further FDA reforms (in line with FDA global strategy) • Emphasizes risk-based approach, foreign inspections (FDA will perform reviews and audits of foreign drug safety programs and standards), greater manufacturer accountability (know your supplier, testing–manage risk/establish safety of raw materials and finished drugs) • Drug supply chain improvements (but no track and trace- possibly to be in a future bill) • Drug shortages (manufacturer notification)

9. GDUFA • S.3187 – “Food and Drug Administration Safety and Innovation Act” (FDASIA) • GDUFA is Section 301 of FDASIA • Bipartisan effort – hardly see these days • Fast approval – moved quickly thru House and Senate • Reconciliation process rapid • Signed by the President on July 9, 2012

13. What’s New at the Office of Generic Drugs/Review Times • New ANDA Requirements • 3 batch requirements for ICH Stability conditions • 3 batch requirements coming for all ANDAs • Size, shape, color issues • Tightening ANDA filing requirements • Monitor Completeness and Acceptability Checklist • Staff time re: GDUFA implementation • Daunting task – lots of meeting, training new employees – takes staff and management away from review time

14. Other Impacts of GDUFA on OGD Program • Coordination of inspections with Office of Compliance • Complete response letter coordination • New review practices…reorganization of CMC reviewers? • Integrating New Drugs into the GDUFA program • Consults – labeling carve out, toxicology, etc. • Office of Chief Counsel and Office of Reg Policy

15. How Does OGD Get to 2015-2017 Metrics? • Last twelve months • Average receipts of originals 92/month (1103) • Average approvals 43 AP/month (479) • Backlog at OGD is at 2933* ANDAs as of 9/30/2012 • To clear backlog at current rate – 2933/517 = 5.67years • If stream of ANDA continue at current pace (1000+/yr) and with the phase in of staffing over 3 years there will be great pressure to meet the 3-5 year metrics

16. User Fee Issues • New User Fees for FY 2013 (PDUFA) (BsUFA)** • Remember Fees for all (b)(2) applications* • Modestly higher fees Only 6.3% • New fees • NDA with clinical data • $1,958,803 • NDA without clinical data • $979,600 • Establishment fees (+1.2%) • $526,500 • Product fees (actual decrease -0.6%) • $98,380 * Small Business waiver for 1st NDA still possible Also Orphan drugs exempt from fee **BPD fee 10% and reactivation fee 20% of PDUFA NDA

17. Generic Drug User Fee “Guesstimate” • GDUFA Fees (estimate based on $299 million) • US Establishment $110-125,000 • X US Estab. $125-140,000 • US API Estab. $ 18 - 25,000 • X US API Estab. $ 30 - 40,000 • Orig. ANDA $ 51,520 • PAS $ 25,760 • Orig. DMF $ 21,340 • ANDA Backlog Fee $ 17,434 *- FDA FR 6/14/12 notice withdrawing about 400 old ANDAs

18. Generics Success Represents Unprecedented Challenge • $931 Billion in savings (2001-2010) has resulted in continued success and growth • While program funding has remained relatively flat… • Generics Industry success has come to represent an unprecedented Regulatory challenge in terms of.. • Size • Scope • Geography

19. Continued Growth in ANDAs 2011 was another historic high

20. DMFs Also Rapidly Growing Multiple references, often years after filing Combined, ANDAs and DMFs are approximately 10 X Plus, the NDA volume

21. Increases in FDF Foreign Inspections

22. Increases in Foreign API Inspections

23. GDUFA Addresses Those Challenges • $299M per year is less than ½ of 1% of Generic Drug sales • And is expected to reduce costs considering the reduced development/regulatory timelines • GDUFA results in less than doubling in OGD over the life of the program • Efficiency enhancement are a critical component of GDUFA • GDUFA is modest size despite 10 X plus the application volume of brands

24. GDUFA Goals Letter Overview

25. Goals Letter Overview • Scope, Assumptions, and Aspirations • Immediate Efficiency Enhancements • Metrics

26. Key Achievements • The program advances critical values • • Timely access to generic drugs • Certainty for industry and FDA • • Safe, high quality generic drugs • • Maintains affordability of generic drugs • • Increases Transparency • • Addresses Globalization • • Advances Regulatory Science

27. Next Steps • Congress Acted – President signed July 9, 2012 • Implementation program – devil in the details • Hiring and training staff • FR Notices and Guidance

31. Contact Information Gordon Johnston Senior Associate Lachman Consultants Westbury, NY 11590 516-222-6222 NY Office 516-805-0379 Cell Email: G.Johnston@LachmanConsultants.com www.LachmanConsultants.com