1. Center for Biologics Evaluation and Research, FDA Site Visit Introduction Michael J. Brennan, Ph.D. for Kathryn M. Carbone, M.D. Associate Director for Research

2. “The Researcher/Reviewer Model is essential to providing CBER with top- level expertise in a regulatory culture.”“The Researcher/Reviewer Model is essential to providing CBER with top- level expertise in a regulatory culture.” -Subcommittee for the External Review -Subcommittee for the External Review of CBER Research, 2/98 of CBER Research, 2/98 Work closely with Regulatory Scientists/Clinical Review Scientists to perform high quality evaluation of novel biological productsWork closely with Regulatory Scientists/Clinical Review Scientists to perform high quality evaluation of novel biological products

4. Evaluation of Research Program Achievements and Proposals Internal & External evaluation of past achievements and research proposals –Internal Management reviews: Yearly cycle using Annual Research Program Reporting Publications, Regulatory Policy/Guidances, Invited talks, Research QA/QC –External Laboratory/Res-Reg/Office Site Visits: 4 yr cycle

5. Site-Visit Team: To evaluate individual PI’s and Service Fellows in a Laboratory Unit RESEARCH accomplishments since last review cycle RESEARCH proposals for next four years –Research Situation –Supervision Received –Guidelines and Originality –Qualifications and Contributions Relative to time for research and research support available Administrative/Management comments welcome Regulatory activities and regulatory work quality NOT assessed by Site Visit Team

6. Site-Visit Team: Suggestions to get or continue “on the right track” Evaluation of the quality of science New research directions and approaches to be considered Needed laboratory expertise Changes in laboratory organization New collaborations

7. Site-Visit Report Oral summary is presented at end of review today to Research Management Written report is prepared with: –Specific comments on each investigator not“On target”, or, if not on target, detailed advice on improvement steps needed –Specific comments on Laboratory Program and Management issues –Specific comments on Personnel issues Conversion Potential Promotion Potential/Cyclical Review for Progress

8. Site-Visit Report Draft report is distributed to full Advisory Committee by Dr. Freas’ staff Final report is approved by full Advisory Committee Final report used for research evaluation and for Evaluation Committee (PCE) review for personnel actions

10. OFFICE OF VACCINES RESEARCH AND REVIEW Center for Biologics Evaluation and Research Michael J. Brennan, Ph.D. Associate Director for Research VRBPAC Site Visit Review November 14, 2007

11. OFFICE OF VACCINES RESEARCH AND REVIEW Division of Bacterial, Parasitic and Allergenic Products. Act. Dir.: Milan Blake, Ph.D. Act. Deputy: Jay Slater, M.D. DIRECTOR Norman Baylor Ph.D. DEPUTY DIRECTOR Florence Houn M.D. Associate Director for Regulatory Policy: Marion Gruber, Ph.D. Associate Director For Management and Scientific Affairs Erik Henchal, Ph.D., F(AAM) Associate Director of Research: Michael Brennan, Ph.D. Special Assistant For Communications Maureen Hess MPH, RD Division of Vaccines and Related Products Applications Act. Dir: Paul Richman, Ph.D. Act. Deputy: Loris McVittie, Ph.D. Division of Viral Products Director: Jerry Weir, Ph.D. Deputy: Philip Krause M.D. Division of Product Quality Dir: William McCormick, Ph.D.

12. OVRR’s Mission Review, evaluate and take appropriate action on INDs, BLAs, and amendments and supplements to these applications for vaccines and related products Plan and conduct research related to the development, manufacture and testing of vaccines, and related products Develop policy and procedures governing the pre-market review and evaluation of vaccines and related products Evaluate and test licensed vaccines and related products as appropriate prior to release and distribution of these products into the market by manufacturers Evaluate and monitor clinical experience and reports of adverse events as necessary in coordination with CBER’s Office of Biostatistics and Epidemiology Participate in inspections of manufacturing facilities Participate in national and international outreach activities, including collaborations with global National Regulatory Authorities

13. Major OVRR Research Priorities 2007 I. Improve or develop new methods that enhance the safety of vaccines and related products II. Improve or develop new methods that enhance the effectiveness of vaccines and related products III. Facilitate the development of new biological products for high-priority public health threats, including emerging diseases and BT agents IV. Develop and evaluate novel scientific technologies and standards to improve biological product regulatory pathways, availability and quality of vaccines and related products

14. Evaluation of OVRR Research Programs Performed on an annual basis using Office Research Priorities Process begins in Divisions -Evaluation of PI Res Prog by Lab Chief-Division Director -Evaluates Research Progress (pubs; presentations; outreach) and Regulatory Workload (INDs, BLAs, Meetings w/ Pharma) Evaluation of Division Research Programs by OVRR through the Scientific Management Committee to address: - FDA regulatory needs - Emerging issues - Future issues ( 2 - 5 years ) - Budget issues Individual Programs evaluated by VRBPAC (site visits) for progress Individual PIs evaluated for promotions by CBER PCE committee

15. Summary The research-regulatory staff support the science-based review and regulation of vaccines and related products. OVRR’s research priorities focus upon our mandate to assure the safety, purity, potency, and effectiveness of vaccines and related products. OVRR’s research program serves to recruit, train and retain highly qualified scientists.

16. Thank you To the Site Visit reviewers for their time, expertise and suggestions for continuing improvement of CBER research programs

18. Division of Viral Products Office of Vaccines Research and Review Jerry P. Weir, Ph.D., Director Phil Krause, M.D., Deputy Director Laboratory of Hepatitis Viruses Steve Feinstone, M.D., Chief Laboratory of Vector-Borne Viral Diseases Lewis Markoff, M.D., Chief Laboratory of Retroviruses Hana Golding, Ph.D, Chief Laboratory of DNA Viruses Andrew Lewis, M.D., Chief Laboratory of Respiratory Viral Diseases Chief - Vacant Laboratory of Immunoregulation Ira Berkower, M.D., Chief Laboratory of Method Development Konstantin Chumakov, Ph.D., Chief

19. Division of Viral Products Mission and Functions Regulate viral vaccines and related biological products, ensuring their safety and efficacy for human use Facilitate the development, evaluation, and licensure of new viral vaccines that positively impact the public health

20. Division of Viral Products Review and Research Activities Investigational new drug (IND) application review Biologics license application (BLA) and supplement review Lot release review and testing Post-marketing activities (e.g., Biological product deviations) Manufacturer inspections Consultation with other public health agencies (e.g., WHO, CDC, NIBSC)

21. Division of Viral Products Review and Research Activities (Cont.) Research activities related to development, manufacturing, and testing of viral vaccines –Viral pathogenesis –Vaccine safety and efficacy (including cell substrates) –Vaccine and viral vector evaluation –Correlates of protection –Reagent preparation (e.g., influenza vaccines) –Methods development and evaluation –Emerging issues (e.g., BSE, counter-terrorism)

22. Laboratory of Method Development Laboratory Teams and their Research Programs –Evaluation of Safety and Potency of Viral Vaccines Based on Molecular Consistency Konstantin Chumakov, Ph.D., D.Sci., Team leader –Microarray-Based Evaluation of Purity and Safety of Biological Products Vladimir Chizhikov, Ph.D, Team Leader –Developing Tests to Evaluate Virus Vaccine Safety for the Nervous System Steven Rubin, M.S., Acting Team Leader

23. Laboratory of Method Development (Cont.) Major Regulatory Responsibilities –Poliovirus vaccines –Measles, Mumps, Rubella virus vaccines –Mycoplasma vaccine issues –Other virus vaccines including parvovirus, varicella virus, ebola, influenza, etc.) Areas of Research –Development of new methods to assess the consistency of viral vaccines –Development of pre-clinical neurotoxicity assays for assuring the safety of live virus vaccines –Development of methods for rapid accurate identification pf biological agents –Evaluation of surrogate endpoints for vaccine safety –Development of methods to detect extraneous agents in vaccines

25. Division of Bacterial, Parasitic and Allergenic Products (DBPAP) Laboratory of Immunobiochemistry Jay Slater, M.D.-Chief Immediate Office of the Director Milan Blake, Ph.D.-Acting Director Jay Slater, M.D.- Acting Deputy Director Regulatory Staff Administrative Staff Laboratory of Methods Development and Quality Control Drusilla Burns, Ph.D.- Acting Chief Laboratory of Respiratory and Special Pathogens Drusilla Burns, Ph.D.-Chief Laboratory of Bacterial Polysaccharides Willie Vann, Ph.D.- Chief Laboratory of Enteric and Sexually Transmitted Diseases Dennis Kopecko, Ph.D.-Chief Laboratory of Mycobacterial Diseases and Cellular Immunology Sheldon Morris, Ph.D.-Chief

26. Laboratory Mission and Functions Dependent on Researcher/Reviewers Conduct regulatory review Conduct critical research: programmatic and special tasks Serve outside organizations as recognized subject matter experts Find outside resources to support research Responsibilities of Researcher/Reviewers

27. Regulatory Review and Laboratory Work: A Synergistic Combination Provide reagents/standards Assay development Improved technology Trouble-shooting Gain expertise to: –Better anticipate issues/identify and fill knowledge gaps –Provide expert input to vaccine community –Provide guidance advice to industry

28. DBPAP Research Priorities 1.Improve or develop new methods that enhance the safety of vaccines and related products 2.Improve or develop new methods that enhance the effectiveness of vaccines and related products 3.Facilitate the development of new biological products for high-priority public health threats, including emerging diseases and BT agents 4.Develop and evaluate novel scientific technologies and standards to improve biological product regulatory pathways, availability and quality of vaccines and related products

29. The Laboratory of Mycobacterial Diseases and Cellular Immunology Areas of Research Evaluation of protective innate and adaptive immune responses to intracellular bacteria Assessment of live attenuated TB vaccine strains and DNA vaccination strategies against tuberculosis Characterization of a unique family of tuberculosis proteins