New Drug Division. Consultant. Chemistry. Biostatistics. Scientific Investigations. Medical Team. Consultant. Project Managers. Inspection.

Transcription

1 PDUFA 4 in Context FDA/Industry Conference Temple University May 2008 RADM Sandra L. Kweder, M.D. Deputy Director, Office of New Drugs Objectives & financial disclaimer Promise of FDAAA PDUFA Good Review Management Practices Implementation of legislation Challenges Reality 2 History What has time taught? Food & Drug Act FD& C Act Kefauver-Harris FDAMA PDUFA FDAAA Regulation driven by science and society Progress can be painful Complex science Tough societal issues Public mood and expectations Change is hard Legislation is blunt: needed for big shifts 3 4 News FLASH! CDER progress predates FDAAA OND quality systems initiative 2002 Integrate therapeutic biologics Improve product and workload organization Meet commitments under PDUFA Balance pre and postmarketing OND Quality Systems Initiative: PDUFA & GRMP Contractor studied NDA/BLA process How reviews are conducted Where information is and how it moves In parallel, developed a workload model Process Analysis Report 35 areas for improvement 5 6 1

2 OND Top 4 areas for improvement NDA/BLA Review Operationalize Good Review Management Practices Postmarket Safety Review Meeting Management Administrative Management Inspection NDA/BLA Review: Quality System Chemistry Scientific Investigations Pharm/Tox New Drug Division Medical Team Project manager Consultant Chief Counsel Biostatistics Consultant t Clinical Pharmacology ACTION Surveillance & Epidemiology 7 8 Seek an orchestra, not a jam Every player matters A PharmTox reviewer is completing her review when a chemist raises a concern about an excipient that wasn t considered. A medical reviewer has conducted analyses of major clinical trials but inspectors are waiting to hear about what should be inspected. IOM report on Drug Safety addresses the need for independence of review Culture of open discourse 9 10 Process Improvement Team All levels of review considered OND Project Managers Division Director and Deputy Consultants across CDER Building in GRMP: The PIT s task Methodical approach Existing Process Analysis Best Practices Many differences; many gaps What are various roles of people involved in NDA/BLA review? Who participates in meetings? Who is in charge of what?

3 New Process under GRMP General Principles Team-based approach with substantive involvement of discipline team leaders and managers throughout Review team members are mutually accountable for raising and addressing differing points of view in a timely manner over the course of the review All reviewers present their work at team meetings General Principles Enhanced Management of the Review Process Roles & responsibilities defined New role: Cross-Discipline Team Leader (CDTL) Ensure scientific and regulatory issues are coordinated and addressed Quality Systems approach facilitates accountability Standard guidelines for managing the team s work, consistent with the GRMP Highlights of New Review Process Highlights of New Review Process Pre-NDA/BLA planning is essential to get a fast start Review begins when the application arrives Filing meeting has multiple purpose Start looking at the END - Review label to identify BIG issues Plan the review strategy (e.g., review schedule, team meetings, involvement of consultants, Advisory Committee) PDUFA 4 Communicate review timeline to applicant Labeling feedback and discussion Postmarketing studies During the review: Continued adherence to timelines Team meets to collaborate regularly Share progress, key analyses & findings Regular cross-discipline interactions at all levels reviewers, team leaders, and division directors Issues are addressed as they arise Structured wrap-up reduces last minute problems (planning) Lessons Learned session with applicant E-o-M 5 E-o-M 6 E-o-M 7 E-o-M 8 E-o-M 9 Mid-Cycle Meeting* Labeling Timeline Team Labeling Meeting 1. The review team works on final draft labeling from month 7 to month Draft labeling sent to applicant by month 7.75 with a 2-week response required. 3. Team reviews revisions -- 1 week. 4. Division Dir. Review of Action Package -- 3 weeks. 5. Labeling Discussions* -- begin 3 weeks before sign-off 6. Signatory review and any final revisions -- 3 weeks. *GRMP Requirements Wrap-Up Meeting* Final Draft Labeling 6 Weeks before Action Date* E-o-M 10 Action Date* Contact Pre-submission from Info Packet Applicant Documented Applicant Interaction Perform Pre-Submission Meeting Activities Summary 1 IT Tools Review of NDA or BLA User Fee Payment New NDA/BLA Submissions, Resubmissions & Amendments Filed Application Conduct Initial Assessment of Recommendation NDA/BLA On Fileability 2 Discipline Filing Reviews EDR Site Central Document Room Conduct Review 3 Applicant Response to Information Requests Completed Reviews and Draft Action Package Issues for AC Conduct Advisory Committee Meeting 4 Outside Experts AC Recommendations Determine Action to Be Taken 5 Priority Designation Filing Review Issues to Applicant Decision Letter to Applicant Final Action Package Invitation to Applicant Provide Post- Action Feedback to Applicant 6 Post-action Feedback For priority applications: Send draft labeling to applicant by month 4.75 with a 1 week response required. This provides 2 weeks to review and make further revisions before the final labeling is required 2 weeks before action date. 17 CDER Staff Time from Submission (Standard/Priority) Day 0 Day 45/30 End of Month 8/5 End of Month 10/6 Concurrent Activities 18 3

4 Benefits to FDA, industry, public Increased discourse across review disciplines Increased consistency across OND divisions Ongoing label discussions with sponsor Helps disciplines contribute more More work satisfaction Fewer problems during wrap-up Confident, sound regulatory decisions Ingredients for Success All part of PDUFA Staff engagement Training Culture shifts Staff - Full House (pdufa) CDER added ~ 400 FTE in 2008 Gradual Implementation (pdufa) Pilot 2008 All NME and new BLA 2009, etc. Complete Applications (GRMP) A goal for 16 years PDUFA is now part of FDAAA PDUFA 4 Promises versus Reality Promise New resources: balance work and staffing Commitment to implement GRMP Commitment to further enhance drug safety Commitment to provide important guidance to industry to improve drug development PDUFA 4 Reality Years to recruit and train new staff authorized in 2008, alone PDUFA workload exceeds capacity of current staff to meet goals and fully implement GRMP PDUFA 4 is only one piece of FDAAA FDAAA provisions further stress the system Bottom line PDUFA performance will get worse before it gets better Resources FY 2008 Staffing just OND HHS personnel 900 system unable to manage current level 840 of need & timing Resources Organization HHS measures to improve will not be felt for some time Office of New Drugs. On Board Ceiling

5 Type PDUFA Workload FY06 FY07 NDA/BLAs NME/BLAs NDA/BLA RS ES RS SPAs Meetings 2256 (2005) 2224 (1906) Implementing FDAAA Safety First OND process improvements were basis for Safety First pre-date FDAAA Every OND Division has Deputy Director & PM for Safety Structured processes between OND & OSE Postmarketing safety issues will be managed with timelines and goals, just like NDA/BLA Safety First & FDAAA (cont.) Promise of FDAAA enhances Safety First New authority related to safety label changes and postmarket studies REMS improved accountability for risk management Reauthorized BPCA and PREA More resources for safety Postmarketing Safety Safety First & FDAAA (cont.) Reality FDAAA provisions are complex Extraordinary legal oversight Implementation uncertainties Same staff are engaged in premarket GRMP and working on PDUFA activities FDAAA & Safety New authorities Better integration of experts in OND & OSE Specified timelines for labeling changes More authority to require postmarketing commitments Stronger postmarketing surveillance Funding for acquisition of databases and collaborations to monitor postmarketing safety Codifies Risk Management Risk Evaluation & Mitigation Strategies (REMS) can be required Resource: Demand How will CDER prioritize work? PDUFA goals are alive and well Existing regulations and policy help Priority vs Standard NDA Type A, B, C meetings, etc. When resources are tight, management must prioritize Thoughtful, consistent, deliberate Avoid blanket decrees

6 Never a dull moment Summary PDUFA 4 is here to stay CDER is committed to implementing GRMP to facilitate high quality application review We will rely on industry for complete applications PDUFA is only one part of FDAAA We must reinvigorate our approach to life-cycle management of drugs safety Resources are robust, but will not be realized for some time CDER will continue to strive for excellence We will stretch, but must prioritize our work Are you making history? FY07 Performance Data 33 NDAs/BLAs FY07 Approvals Med. Total Time FY06 Approvals Med. Total Time All priority All standard NME priority NME standard Goals & values synergize change GRMP Goals Enhanced communication within FDA and with applicants Consistency in key processes across CDER and CBER Strengthened management of the review process and team- based reviews OND Values Quality of the collective review and the regulatory action Process Efficiency Clarity of findings, expectations, and bases for decisions Transparency of review progress; opportunity for early remedial actions Consistency across OND 35 6