Laboratory of Methods Development and Quality Control

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Laboratory of Methods Developmentand Quality
Control

• Laboratory Overview
• September 22, 2005

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LMDQC research and regulatory activities

• Clinical Immunoassay
• Assays used for clinical evaluation
• Development of animal models that support Animal
  Rule
• Product Testing and Quality Control
• Tests for potency, toxicity, and purity
• Implementation of laboratory quality system
• Quality control of official testing activities

• Goal Testing specialists activities not
• limited to a specific product area

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Laboratory of Methods Development and Quality
Control
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Laboratory History

• September 1997 (last site visit)
• Laboratory of Pertussis
• Biochemistry (Burns)
• Applied Immunology and Vaccine Evaluation (Meade)
• February 1998
• Assumed responsibilities for anthrax vaccines
• October 1999
• Laboratory of Respiratory and Special Pathogens
• Laboratory of Methods Development and Quality
  Control

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LMDQC vs. LRSP

• LRSP Product area specialists
• Is it the right test? (Relevance)
• Is the test addressing the appropriate
  characteristic of the product and/or immune
  response?
• LMDQC Testing specialists
• Is the test right? (Reliability)
• Is the test adequately designed and controlled?
• Is the test adequate for intended purpose?

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Laboratory of Methods Development and Quality
Control

• Regulatory
• Review (i.e., non-laboratory regulatory
  activities)
• Quality Control Laboratory (product testing)
• Research
• Research program under review
• Specific products
• Pertussis
• Anthrax (1998)
• Others

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Overview of Regulatory Activities

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LMDQC Regulatory Activities

• Licensing
• Pre-approval
• Investigational New Drug applications (IND)
• Biologic Product License applications (BLA)
• Post-approval
• Supplements to BLA (manufacturing /or clinical)
• Product areas
• Pertussis, anthrax, diphtheria, cholera, Lyme,
  typhoid, malaria
• Animal Rule
• Animal models used to evaluate efficacy
• Assays used to demonstrate that the functional
  immune response in humans is comparable to that
  shown to be protective in relevant animal models

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LMDQC Regulatory Activities

• Establishment inspections
• Product experts for pre and post-approval
  inspections
• Lot release
• Prior to commercial distribution, lots of
  licensed vaccine must be released by CBER based
  on
• Review of documentation on manufacturing and
  testing
• Testing (optional) of submitted samples
• International harmonization and standardization
• CBER initiative to implement quality system
• LMDQC lot release coverage
• 6 licensed products with pertussis component
• 1 licensed anthrax vaccine

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Overview of Research Activities

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Areas of responsibility research

• Clinical Immunoassay (Bruce Meade)
• Assays used in clinical evaluation
• Humans
• Animal models in support of licensing Animal
  Rule
• Product Testing and Quality Control (Juan
  Arciniega)
• Tests for potency, toxicity, and purity

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Clinical Immunoassay Projects (Meade)

• Pertussis Vaccine
• Serologic Diagnosis of Pertussis
• Development and evaluation of simple, easily
  transferable immunoassay for IgG anti-PT
• Collaboration with CDC
• Statistical Methods Use of Coefficient of
  Variation
• Nomogram
• Safety and immunogenicity of 4th and 5th doses of
  DTaP
• Anthrax Vaccine
• Collaborative Study Anthrax Clinical Immunoassays

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Product Testing and Quality Control Projects
(Arciniega)

• Pertussis Vaccine Projects
• Refinement of a toxicity test for acellular
  pertussis vaccines
• International Collaborations Pertussis Test
  Methods
• Anthrax Vaccine Projects
• Anthrax Vaccine Potency Test Development
• Mouse immunogenicity model
• Anthrax Vaccine Standards Development
• Anthrax Vaccine Formulation Studies
• HPLC Methods for Monitoring Antigens and
  In-Process Control
• Diphtheria Vaccine Projects

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Relevance of Research to Regulation

• State-of-the-art knowledge of the areas we
  regulate
• First-hand expertise to
• Design and evaluate tests used in assessment of
  product quality and effectiveness
• Troubleshoot problems encountered by manufacturer
• Contribute to international harmonization
• Design the efficacy studies for vaccines licensed
  under the Animal Rule
• Credibility in the field
• Problem solving approach

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Impact of Research on Regulatory Mission Examples

• Acellular pertussis vaccines
• Clinical immunoassay
• Developed procedures
• Served as international reference laboratory
• Applied immunoassays to clinical studies
• CBER mouse immunogenicity test served as basis
  for potency test described in WHO guidelines and
  EP monographs
• Anthrax vaccine
• Applying bioassay experience to animal efficacy
  models
• Developing mouse immunogenicity test (potency)
• Assisting in optimizing and standardizing assays
  for clinical and product evaluation
• Diphtheria vaccine
• Participating in collaborations aimed at
  development of alternative animal models