Center for Biologics Evaluation and Research, FDA

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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

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

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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

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Site-Visit Team To evaluate individual PIs 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

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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

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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 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

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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

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OFFICE OF VACCINESRESEARCH AND REVIEWCenter
for Biologics Evaluationand Research
Michael J. Brennan, Ph.D. Associate Director for
Research VRBPAC Site Visit Review November 14,
2007
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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.
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OVRRs 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 CBERs 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

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Major OVRR Research Priorities 2007
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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

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Summary

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

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Thank you

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

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Division of Viral ProductsOffice 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 DNA Viruses Andrew Lewis, M.D.,
Chief
Laboratory of Respiratory Viral Diseases Chief -
Vacant
Laboratory of Method Development Konstantin
Chumakov, Ph.D., Chief
Laboratory of Immunoregulation Ira Berkower,
M.D., Chief
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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

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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)

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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)

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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

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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

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Division of Bacterial, Parasitic and Allergenic
Products (DBPAP)
Laboratory of Mycobacterial Diseases and
Cellular Immunology Sheldon Morris, Ph.D.-Chief
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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
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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

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DBPAP Research Priorities

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

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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