2. CBER Research: OCTGT Office Site Visit Carolyn A. Wilson, Ph.D. Associate Director of Research (Acting) CBER/FDA

3. CBER’s Mission To ensure the safety, purity, potency, and effectiveness of biological products, including vaccines, blood and blood products, and cells, tissues and gene therapies for the prevention, diagnosis, and treatment of human diseases, conditions or injury.

4. Vision for CBER Protect and improve public and individual health in the US and, where feasible, globally Facilitate development, approval and access to safe and effective products and promising new technologies Strengthen CBER as a preeminent regulatory organization for biologics INNOVATIVE TECHNOLOGY ADVANCING PUBLIC HEALTH

5. Critical Products for Public Health, National Preparedness & 21 st Century Medicine Blood Derivatives Devices Whole Blood Tissues Xenotransplantation Somatic Cell & Gene Therapy Vaccines Allergenics Blood Components 30 million235 million 1 million Devices

6. CBER’s Approach to Regulation External Discussion Active Research at CBER Review of Data Submitted to IND Internal CBER Discussion

7. Multitasking at the FDA: Research Supports Regulatory Mission CBER researchers fully integrated into the regulatory process (~50% average time)= “Researcher-Regulator” –Review INDs, BLAs, 510ks, PMAs, IDEs, HDEs –Development of Policy and Guidance Documents –Meeting with Sponsors and Advisory Committees –Participation in Pre-license and Biennial Inspections –Evaluation of Adverse Drug Reactions and Risk Assessment –Performing research relevant to product evaluation of safety, efficacy, manufacturing: Developing/evaluating scientific tools & knowledge –Outreach, communication with stakeholders

8. CBER Research Solutions Prepare for long-term programmatic needs AND for crisis responsiveness Outcomes driven: Identifying and resolving specific, high priority scientific challenges in product evaluation –PRODUCT DRIVEN, expertise supported Focus on critical gaps in scientific tools and knowledge for product evaluation Support product development for critical, unmet public health needs Where feasible, multidisciplinary, coordinated team research for regulatory challenges –Internal and External Communication

9. CBER Research Should: Encompass the scientific basis of manufacturing, pre-clinical and clinical studies. Outcomes should be taken into account in regulatory decisions, inspections, postmarketing surveillance and Guidances. Aim for high quality, efficient, and directed research, managed to provide outcomes addressing scientific and regulatory challenges in product development, safety, efficacy and quality. Where feasible, be highly collaborative, including laboratory, epidemiological, statistical, and clinical sciences. CBER Research Management Guiding Principles

10. CBER RESEARCH MANAGEMENT OVERVIEW 1.IDENTIFICATION OF REGULATORY AND PUBLIC HEALTH NEEDS 2. CBER RESEARCH PRIORITIES 3. OFFICE RESEARCH PLANS AND PRIORITIES 4. RESEARCH PROGRAMS EXTERNAL REVIEW AND INPUT

11. Regulatory Workload Analysis 1. IDENTIFICATION OF REGULATORY AND PUBLIC HEALTH NEEDS Key Policy Activities Public Health & Emerging Issues (horizon scanning) Staff: Research-regulators Review-regulators Management External Input: Scientific Meetings/Workshops Advisory Committees Site Visits

12. 2. CBER RESEARCH PRIORITIES Regulatory and Public Health Needs Impact on Facilitating Product Development Product Quality, Safety & Efficacy Unique CBER Expertise

13. FY08 Research Priorities - 1* Improve or develop new methods to measure and augment biological product safety and efficacy. Evaluate, develop, integrate novel scientific technologies to improve biologics product regulatory pathways, availability, quality. Facilitate the development of new biological products for high priority public health threats, including pandemic influenza, emerging infectious diseases, and agents of bioterrorism. *Developed by CBER’s Research Leadership Council

14. Improve clinical trial design and evaluation, including adaptive design approaches Develop formal risk management and risk assessment approaches Enhance safety surveillance by developing improved analytical tools and accessing large databases (CDC, Medicare, etc) FY08 Research Priorities - 2

15. Examples of CBER’s Research Identified as High Priority* OBE: Analyzing of Healthcare databases for biological safety and effectiveness evaluation OBRR: Using proteomics to identify biomarkers predictive of stored RBC and platelet efficacy OCTGT: Improving the safety and efficacy of adenovirus vectors for gene therapy OVRR: Developing in vitro assays predictive of in vivo toxicities of novel vaccine adjuvants *Selected for Critical Path Funding in FY08

16. 3. OFFICE RESEARCH PLANS AND PRIORITIES 2. CBER RESEARCH PRIORITIES Regulatory Workload Analysis Key Policy Activities Public Health & Emerging Issues (horizon scanning) Research Program Review and Evaluation

17. ANNUAL REVIEW BY OFFICES relevance, quality, productivity FOUR YEAR RESEARCH PROGRAM EVALUATION External Site Visit PCE cyclical review Research Program Review and Evaluation 3. OFFICE RESEARCH PLANS AND PRIORITIES

18. Annual Review of Research Programs by Offices Web-based Research Reporting –Achievements Scientific publications Relevant Guidance Documents Presentations at scientific meetings, workshops, advisory committees –Future plans Reviewed by Office Leadership: –Lab/Branch Chief –Division Director –ADR/Office Director

19. Rating Research Program Success Achievements –Return on research resources expended Direct impact of research on regulatory challenges Quality: Peer reviewed publications & invited talks Contribution to Guidances, policy, workshops –Impact on international harmonization –Review workload and quality Future Research Plans-short & long term –Unique CBER Expertise contribution –Priority area & response to public health issue –Direct impact on regulatory challenge –Feasibility: Expertise, collaborations, infrastructure –Quality –Return on investment

20. 4 Year Cycle External Review: Scientific Expertise Site Visits Site Visit Team –Subcommittee of relevant CBER Advisory Committee –Chaired/Co-chaired by two Advisory Committee Members –Supplemented with appropriate outside Scientific Experts Site Visit Team reviews each Laboratory unit –Researcher-Reviewers (PI’s) & their Research Programs –PI’s prepare and submit detailed material: Achievements past four years Proposal for research next four years –Formal presentations to Site Visit Team –Site Visit Team holds individual interviews with each PI Site Visit Team drafts report presented to full Advisory Committee for approval

21. 4 Year Cycle Internal Review: Promotions & Conversions Evaluation Committee All Researcher-Regulator staff are evaluated: –Conversion to permanent staff –Promotions to GS-13 or higher –Every four years for cyclical progress review Review is by Senior Researcher-Regulator and Regulatory Scientists from each product Office Review includes –Regulatory workload & quality assessment –Research productivity, mission relevance and quality assessment Managed by Center ADR to provide recommendations to Center Director on personnel actions & cyclical review assessments for all Researcher-Reviewer Staff Formal SOP & procedures established in conjunction with Office of the Commissioner’s Peer Review policy

22. CBER RESEARCH MANAGEMENT OVERVIEW 1.IDENTIFICATION OF REGULATORY AND PUBLIC HEALTH NEEDS 2. CBER RESEARCH PRIORITIES 3. OFFICE RESEARCH PLANS AND PRIORITIES 4. RESEARCH PROGRAMS EXTERNAL REVIEW AND INPUT

23. Advisory Committees’ Review of CBER’s Research Programs by Office, 2005-6 “Committee members who have been familiar with the research programs…over a period of years note that there has been a striking improvement over time…: –Focus and relevance …The research presented for this review had direct relevance to the Critical Pathway of biologics product development and availability. –Quality. …the quality of the research has also improved; many of the ongoing studies are equal in quality to those in the intramural program at the National Institutes of Health (NIH) and of sufficient caliber to compete for RO1 and other NIH grants.”

24. “Committee…strongly supports the FDA’s continued emphasis on the importance of having a strong intramural research program to support its Critical Pathway program for effective and efficient regulatory activities… If we are to maintain our lead in health care development in the USA, regulatory science needs to be given the priority it deserves, independent of the short-term political and economic flurries that can derail progress.” Advisory Committees’ Review of CBER’s Research Programs by Office, 2005-6

25. Advisory Committees’ Review of CBER’s Research Programs by Office, 2005-6: STRENGTHS IDENTIFIED Productivity, scientific merit, mission relevance Well recognized for outreach efforts Complementary cross-Office expertise Success at recruitment and retention Core facilities Leveraging and collaboration (NIH, CDC, NTP, Academia)

26. Increased regulatory workload, decreasing support Best mechanism: Balance managing mission relevance of research vs. micromanagement Covering many research bases vs. focus on quality in fewer areas Development of an explicit plan/strategic plan for 2-5 year priority research needs with regulatory and stakeholder input Advisory Committees’ Review of CBER’s Research Programs by Office, 2005-6: CONCERNS, I

27. Mentoring Recruitment and retention Increased research program visibility Continuing education support Increased collaboration within and outside FDA Increased FDA base funding support for research Creative leveraging support, e.g., FDA based Foundation for Research (like Jackson Foundation for DOD) Need a public relations campaign Need a system of reward for successful research Advisory Committees’ Review of CBER’s Research Programs by Office, 2005-6: CONCERNS, 2

28. Report of the Subcommittee on Science and Technology Prepared for the FDA Science Board, November, 2007 “…CBER has a rigorous process for establishing priorities and the impact of Center research on regulation. In addition, the leadership of CBER insists upon integration of laboratory scientists both in the review and manufacturing site inspection process. External peer review of research programs is the norm rather than the exception.” “…CBER has a rigorous process for establishing priorities and the impact of Center research on regulation. In addition, the leadership of CBER insists upon integration of laboratory scientists both in the review and manufacturing site inspection process. External peer review of research programs is the norm rather than the exception.”

29. THANK YOU For your time, expertise, and input into our research programs.