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

• ““The Researcher/Reviewer Model is The Researcher/Reviewer Model is essential to providing CBER with top-essential to providing CBER with top-level expertise in a regulatory culture.”level expertise in a regulatory culture.”

-Subcommittee for the External Review -Subcommittee for the External Review

of CBER Research, 2/98of CBER Research, 2/98

• Work closely with Regulatory Work closely with Regulatory Scientists/Clinical Review Scientists to Scientists/Clinical Review Scientists to perform high quality evaluation of novel perform high quality evaluation of novel biological productsbiological products

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

Site-Visit Team: To evaluate individual PI’s Site-Visit Team: To evaluate individual PI’s and Service Fellows in a Laboratory Unitand 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

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

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

• “On target”, or, if notnot 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

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

OFFICE OF VACCINESRESEARCH AND REVIEW

Center for Biologics Evaluationand Research

Michael J. Brennan, Ph.D.Associate Director for Research

VRBPAC Site Visit Review November 14, 2007

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.

DIRECTORNorman Baylor Ph.D.

DEPUTY DIRECTORFlorence Houn M.D.

Associate Directorfor Regulatory Policy:Marion Gruber, Ph.D.

Associate Director For Management and Scientific Affairs

Erik Henchal, Ph.D., F(AAM)

Associate Directorof Research:

Michael Brennan, Ph.D.

Special Assistant For Communications

Maureen Hess MPH, RD

Division of Vaccines and Related Products ApplicationsAct. Dir: Paul Richman, Ph.D.

Act. Deputy: Loris McVittie, Ph.D.

Division of Viral ProductsDirector: Jerry Weir, Ph.D.Deputy: Philip Krause M.D.

Division of Product QualityDir: William McCormick, Ph.D.

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

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 theeffectiveness of vaccines and related products

III. Facilitate the development of new biological productsfor 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

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

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.

Thank you

• To the Site Visit reviewers for their time, expertise and suggestions for continuing improvement of CBER research programs

Division of Viral ProductsOffice of Vaccines Research and

ReviewJerry P. Weir, Ph.D., Director

Phil Krause, M.D., Deputy Director

Laboratory of Hepatitis Viruses

Steve Feinstone, M.D., ChiefLaboratory 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

Division of Viral ProductsMission 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

Division of Viral ProductsReview 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)

Division of Viral ProductsReview 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)

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

Laboratory of MethodDevelopment (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

Division of Bacterial, Parasitic and Allergenic Products (DBPAP)

Laboratory of ImmunobiochemistryJay Slater, M.D.-Chief

Immediate Office of the Director

Milan Blake, Ph.D.-Acting DirectorJay Slater, M.D.- Acting Deputy Director

Regulatory Staff Administrative Staff

Laboratory of Methods Development andQuality 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

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

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

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

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