FDA AA - Title I

1. FDA AA - Title I PDUFA IV & FDA’s Performance Goals Friday, 30 November 2007 MBC Naseem Kabir Associate Director Regulatory Affairs

2. FDAAA & FDA’s PERFORMANCE GOALS

3. PDUFA IV (Parts I-VII): What is New? FDA’s fee revenue amounts have increased

4. PDUFA IV (Parts I-VII): What is New? • Additional $225 million of revenues for drug safety reflected in user fees • $25,000,000 for fiscal year 2008; • $35,000,000 for fiscal year 2009; • $45,000,000 for fiscal year 2010; • $55,000,000 for fiscal year 2011; and • $65,000,000 for fiscal year 2012

5. PDUFA IV (Parts I-VII): What is New? • Additional criteria for orphan drugs to request exemption from product and establishment fees • The drug is owned / licensed and is marketed by a company that had less than $50,000,000 in gross worldwide revenue during the previous year • Must submit certification that gross annual revenues < $50,000,000 for the preceding 12 months before the exemption was requested

6. PDUFA IV (Parts I-VII): What Remained the Same? • FDA’s performance goals for application reviews • Orphan drugs continue to remain exempt from user fees for review of applications • Performance goals for clinical holds, major dispute resolution and SPAs • Requirement to pay annual prescription drug establishment fees and product fees

7. PDUFA IV (Parts I-VII): What Remained the Same? Original & Resubmitted NDAs/BLAs & Efficacy Supplements Manufacturing Supplements

8. PDUFA IV (Parts I-VII): What Changed Slightly? • An application/supplement that is submitted but refused for filing, or withdrawn before being accepted/refused for filing is subject to full review fee upon resubmission (unless waived/reduced) • FDA’s performance goals for meeting management remain unchanged except: • Type B and C: 90% within 21 calendar days of FDA receipt

9. PDUFA IV (Parts I-VII): What Changed Slightly? User fee increases

10. Part VIII: Enhancement and Modernization of the FDA Drug Safety System FDA to develop a 5-year plan to modernize drug safety activities & systems, emphasizing: • new methodologies in the collection of AE info throughout the product life cycle; • epidemiology best practices and guidances; • CDER/CBER database acquisition and expansion; • validation, development of risk management / communication tools; • improved post-market IT systems / linkages, and • enhanced coordination between FDA offices and teams (CDER and CBER, pre-market and post-market)

11. Part VIII: Enhancement and Modernization of the FDA Drug Safety System FDA will conduct and support activities designed to modernize PV by: • Maximizing public health benefit of AE collection throughout product life cycle • RFP published in 2008, awarded 2009, completed by 2011 • Contractors will critically review US, ex-US AE collection B. Developing an epidemiology ‘best practices’ and guidance document • Public workshop in 2008; review current practice in US, ex-US • CDER and CBER to release joint guidance in 2010

12. Part VIII: Enhancement and Modernization of the FDA Drug Safety System FDA will conduct and support activities designed to modernize PV by: (cont..) C. Expanding database resources • Not just AERS, but population-based epidemiologic data • Targeted PM surveillance, signal detection • FDA to purchase epi (observational) DB, hire additional epi staff D. Developing, validating risk management and risk communication tools • Evaluate effectiveness of RiskMAPs • Public workshop in 2009: assess current risk management / risk communication options • Annual systematic review of select risk management programs & tools

13. Part VIII: Enhancement and Modernization of the FDA Drug Safety System • Impact on Industry: • Outcome of the 5-year plan is likely to bring about a dramatic shift in PV, with consequences to all PV processes and procedures • Increasing importance of risk management PE will impact resources, training, and necessary skill sets • PE will become increasingly critical to support PM safety activities and commitments • IT systems thus created will need to be updated to accommodate new requirements • PDUFA IV represents a significant shift towards a life-cycle approach to risk management

14. PART IX: REVIEW OF PROPRIETARY NAMES • Objective is to reduce medication errors • Opportunity to submit brand name during the IND process (instead of during NDA) and to obtain FDA feedback earlier • Pilot program to be implemented in FY 09 • Allows companies to submit their research on the brand names, which FDA can evaluate to provide decision

15. PART X: First Cycle Review Performance Day-74 Letters: Notification of Issues Identified During Filing • Will identify substantive review issues during the filing review (for original NDA/BLA applications and efficacy supplements) • Notification also sent if no substantive issues identified • Not indicative of deficiencies that may be identified later in the review cycle • To include planned review timelines (including dates for feedback on labeling and post-marketing commitment discussions) • Allows companies to better plan workload • Solid strategy on submission content • Submission of major amendments may nullify timelines

16. PART XI: Expediting Drug Development • FDA to develop guidance documents to further the Critical Path Initiative • Clinical Hepatotoxicity – FY 2008 • Non-inferiority Trials – FY 2008 • Adaptive Trial Designs – FY 2008 • End of Phase 2(a) Meetings – FY 2008 • Multiple Endpoints in Clinical Trials – FY 2009 • Enriched Trial Designs – FY 2010 • Imaging Stds for Use as an EP in Clinical Trials – FY 2011 • Ongoing collaboration with scientific community to develop guidances on: • Predictive Toxicology • Biomarker Qualification • Missing Data • FDA participation in public workshops to explore new approaches to develop a structured model for benefit/risk assessment. Goal is to evaluate pilots and development of guidance documents

17. PART XII: Post-Marketing Study Commitments FDA commits to: • Developing harmonized (CBER/CDER) SOPs that articulate the Agency’s policy and procedures (e.g., timing, content, rationale and vetting process) for requesting that applicants agree in writing to “voluntary post-marketing study commitments” • What will “voluntary” mean to industry? • SOPs will be finalized prior to the end of FY 08 • Training will be provided to all CBER and CDER review staff on the SOPs as necessary through FY 12 From industry perspective: • Must strategically consider consequences of PMCs and negotiate accordingly • Part XII extends possibility of FDA requesting PMCs for previously approved drugs

18. PART XIII: IMPROVING FDA PERFORMANCE MANAGEMENT FDA will conduct studies to: • Assess the impact of the electronic submission and review environment on the efficiency and effectiveness of the overall process for the review of human drugs • Assess the progress toward full implementation of Good Review Management Principles, focusing on both FDA reviewer practices and industry sponsor practices affecting successful implementation

19. Part XIV: IT Goals • 5-year plan will include: • new safety system (previously referred to under Drug Safety) • a roadmap for all IT plans intended to support the goal of end-to-end electronic communications • Plan will be updated as FDA deems necessary to achieve the IT objectives • Communications and Technical Interactions: • FDA and industry stakeholders will meet on a quarterly basis to discuss: • Discuss on-going implementation of the IT Plan • Status of IT metrics as available • Potential impacts of future activities on stakeholders • Revisions to the IT Plan

20. Part XIV: IT Goals Metrics & Measures • Numbers and types of applications received (NDA, BLA, IND, etc.) • Total number of submissions categorized by type of submission • Total number of submissions in valid electronic format in compliance with FDA standards • The number and type of failure areas for electronic submissions out of compliance • Total number of submissions received through the secure electronic single point of entry versus other methods • Total number of submissions received substantially on paper.

21. SECTION B FEES RELATING TO ADVISORY REVIEW OF DTC TV ADS Overview of Legislation • Authorizes FDA to assess/collect user fees for advisory review of drug DTC TV ads • Medical device DTC TV ads not impacted at this time • Voluntary Program • Notify FDA in advance of # of DTC TV ads intended for next FY • FDA issued FR notice for companies wishing to participate in FY 2008 • Legally binding commitment to pay fees • ≤$83,000 per submission in FY2008 • to be paid up front for # of reviews requested • FDA will commit to providing advisory review in specified period of time

22. For Further Info My contact info naseem.kabir@genzyme.com FDAAA website http://www.fda.gov/oc/initiatives/advance/fdaaa.html#actions PDUFA website http://www.fda.gov/oc/pdufa/ FDA Performance Goals http://www.fda.gov/oc/pdufa4/pdufa4goals.html

23. Questions?