FDAs Critical Path Initiative Office of Vaccines Research and Review Update February 17, 2005

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FDAs Critical Path InitiativeOffice of
VaccinesResearch and ReviewUpdate - February
17, 2005

• Jerry P. Weir, Ph.D.
• Division of Viral Products

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The Critical Path to New Medical Products

• March 16, 2004 FDA released report entitled
  Innovation/Stagnation Challenge and Opportunity
  on the Critical Path to New Medical Products
• Describes the urgent need to modernize the
  medical product development process the
  Critical Path to make product development more
  predictable and less costly
• FDA will take the lead in development of a
  national Critical Path Opportunities List with
  the goal of coordinating, developing, and/or
  disseminating solutions to scientific hurdles
  that are impairing the efficiency of product
  development industry-wide
• www.fda.gov/oc/initiatives/criticalpath
• CBER Workshop October 7, 2004

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Working With Stakeholders onScientific
Opportunities for Biologic Products

• Participants in workshop included representatives
  of industry, academia, other government agencies,
  and the public
• CBER staff presented overviews of current and
  future scientific opportunities
• Cell, Tissue and Gene Therapies
• Blood and Blood Products
• Manufacturing Science
• Statistics, risk management and clinical trial
  design
• Vaccines
• Break-out sessions with panel discussions

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Overview of the Laboratories in the Office of
Vaccines Researchand Review

• Immediate Office of the Director
• Standards and Testing Section
• Analytical Chemistry Staff
• Division of Viral Products
• Laboratories of DNA Viruses, Retrovirus Research,
  Hepatitis Viruses, Vector-Borne Viral Diseases,
  Immunoregulation, Method Development, Respiratory
  Diseases
• Division of Bacterial, Parasitic and Allergenic
  Products
• Laboratories of Immunobiochemistry, Biophysics,
  Enteric Sexually Transmitted Diseases,
  Bacterial Polysaccharides, Methods Development
  Quality Control, Mycobacterial Diseases
  Cellular Immunology, Bacterial Toxins,
  Respiratory Special Pathogens

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Facilitating the Development and Evaluation of
New Vaccines

• Anticipating and Addressing the Regulatory Issues
  for New Products
• General regulatory issues applicable to many
  products or product classes
• Cell substrate issues
• Improved test methods (sensitivity, reliability,
  etc.)
• Product specific issues
• Correlates of protection necessary for efficacy
  evaluation
• Improved assays (e.g., potency, efficacy)
• Animal models for efficacy evaluation
• Prioritizing Research Efforts
• Availability of necessary expertise
• Appropriateness of research effort
• Competing demands

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Some Examples of Critical Path Efforts Applicable
to Many Vaccines

• Development of Alternative Lot Release Tests
• Increased product availability
• Reduce animal testing
• Recent examples include rabies potency, mumps
  neurovirulence, anthrax potency, and diptheria
  toxoid potency
• Development of Rapid Microbial Tests
• Improve current products and facilitate
  evaluation of new vaccines
• Reduce time and amount of product needed
• Evaluation of novel cell substrates for vaccine
  production
• Develop new molecular methods to detect broad
  categories of potential adventitious agents
• Development of new assays to assess
  tumorigenicity and oncogenicity and to detect
  oncogenic viruses

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Some Examples of Critical Path Efforts for
Priority Viral Vaccines

• Hepatitis C
• Development of transgenic mouse models to study
  pathogenesis and evaluate candidate vaccines
• HIV
• Development of new assays to distinguish vaccine
  response from HIV infection Identification of
  target structures and epitopes for neutralizing
  antibodies
• Smallpox
• Improved assays to evaluate vaccine response
  animal models
• West Nile Virus
• Development of standardized immunological assays
  for vaccine induced immunity
• Poliovirus Vaccines
• Development of animal models to evaluate efficacy
  of Sabin-derived IPV
• Influenza Vaccines
• Development and standardization of reference
  strains and reagents for evaluation of pandemic
  influenza vaccines

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Some Examples of Critical Path Efforts for
Priority Bacterial Vaccines

• Anthrax
• Development of animal models of pathogenesis
• Development of serological assays
• Development of Ty21a vector for PA
• Establish tools for genetic manipulation of the
  pathogen
• Tuberculosis
• Discovery of novel antigens with protective
  properties
• Evaluation of DNA vaccines
• Shigella
• Creation of Ty21 vector of shigella LPS
• Pneumococcus
• Identification of serological correlates of
  protection
• Meningitis
• Development of high-efficiency conjugation
  technology
• Establishment of correlates of protection

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Summary and Future Directions

• Numerous scientific, technical, and regulatory
  challenges must be addressed in the development
  of new and improved vaccines
• General regulatory issues
• Product specific issues
• Challenge of vaccine development for emerging
  diseases
• OVRR researcher/reviewers have a major role in
  identifying and anticipating such issues
• Clear guidance regarding expectations for product
  development and licensure
• Guidance documents (e.g., revised cell substrate
  and DNA vaccines guidance)
• CBER research activities necessary to address
  certain issues with regulatory implications
• Product development
• Product evaluation

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Vaccines Breakout and Panel Discussion

• List of Panelists
• Gary Overtuff, M.D. (Univ. New Mexico)
• Alan Shaw, Ph.D. (Merck)
• John La Montagne, Ph.D. (NIH/NIAID)
• Robert Jay Reinhard (AVAC)
• Laurie Norwood, M.S. (CBER/OCBQ)
• Panelists provided their perspective of the
  vaccine development process
• Floor opened to discussion
• Brief summary of discussion presented to larger
  group

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Summary of Panel Discussion

• The process of vaccine development should be
  re-engineered
• Many aspects of current process are not optimal
  (e.g., complex and cumbersome IRB process, burden
  of data management, lack of sharing of
  information about trial design, etc.)
• Importance of establishing and validating
  surrogate endpoints for vaccine trials
• Importance of communication
• Detailed guidance for industry also more
  guidance for those with limited experience in
  vaccine development
• Long-term follow-up and post-licensure
  surveillance
• CBER research can and should assist vaccine
  development
• More pre-clinical studies
• Studies on novel antigens
• Studies on adjuvants
• Vaccine delivery methods
• Rational vaccine design including defining
  surrogate markers

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Next Steps

• Continue compilation of opportunities list
• Additional workshops on specific diseases,
  products, pathways, etc.
• Summarize and publish the discussions from the
  CBER Workshop
• Develop future CBER science priorities and agenda
• Communicate scientific advances in Guidances,
  policy and publications