Division of Bacterial, Parasitic and Allergenic Products OVRR/CBER/FDA

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Division of Bacterial, Parasitic and Allergenic
ProductsOVRR/CBER/FDA
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Laboratory Mission and Functions
Assure Safe and Effective Products for
Immunological Control of Bacterial, Parasitic and
Allergenic Agents Affecting Human Health

• Research
• Review
• Post-licensure surveillance
• Inspection/compliance
• Lot release testing/protocol review
• Label/promotional activity review
• Consultations with outside organizations

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DBPAP Role in Regulatory Review and Approval
Pre-IND IND
License

• Meeting with
• sponsors to
• provide guid-
• ance

• Rev. of orig.
• Submission
• all subsequent
• ammendments
• Tech. Advice for
• product and
• assay development
• Rev. product manf.
• data determin-
• ation of prod. specs.
• Meet with sponsors

• Present prod. To
• Advisory Comm.
• Meet with spon-
• sors
• Eval. Assays to
• measure clinical
• response to prod.
• Eval. product
• characterization
• methods assays

• Rev. of final prod.
• manuf. process, in-
• cluding in process
• final product specs.
• Est. lot release protocols
• for CBER product
• release
• Conduct pre-approval
• inspection of the
• facility

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DBPAP Role in Regulatory Review and Approval
Pre-IND IND License Post
Licensure

• Review of Biological Deviation
• reports from industry
• Participation in biannual
• inspections of licensed products
• Review of post approval
• commitments
• Review of subsequent supplements
• for changes to maufacture or
• additional indications
• Meet with sponsors

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Possible New or Improved Products

• Respiratory Pathogens
• Streptococcus pneumoniae
• Mycobacterium tuberculosis
• Pseudomonas aeruginosa
• Neisseria meningitidis A,B,C,Y,W125
• Group B Streptococci
• Bordetella pertussis
• Chlamydia pneumoniae
• Corynbacterium diphtheriae
• Non-typeable H. influenzae
• Moraxella catarrhalis
• Sexually Transmitted Pathogens
• Neisseria gonorrheae
• Chlamydia trachomatis

• Pathogens Encountered by Penetrating Inoculation
• Borrelia burgdorfi
• Plasmodium species
• Leishmania species
• Clostridium tetani
• Staphylococcus aureus
• Schistosoma species
• Trypanosoma cruzi
• Special Pathogens (BT)
• Bacillus anthracis
• Clostridium botulinum
• Franciscella tularensis
• Yersinia pestis

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Possible New or Improved Products

• Diarrhea-Causing Pathogens
• Enterotoxigenic E. coli
• Shigella species
• Vibrio cholerae
• Campylobacter jejuni
• Other Mucosally-Trafficking Pathogens
• Clostridium difficile
• Salmonella typhi
• Mycobacterium leprae
• Helicobacter pylori
• STEC and EPEC

• Allergenic Antigens
• Latex
• Cockroach
• Short ragweed
• Skin Test Antigens
• PPD
• Coccidioidin
• Leishmania

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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 of Methods Development and Quality
Control

• Research activities
• Develop and evaluate
• Quality control methods for bacterial vaccines
• Serological methods for immune response
  measurement
• Animal models
• Gastrointestinal anthrax
• Bioassays for potency and toxicity
• Issues and observations
• Recruiting for 1 position
• Lab chief

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Laboratory of Biophysics

• Areas of Research
• Characterization of biopolymers (polysaccharides,
  proteins DNA) and macromolecular assemblies
  (vaccine/adjuvant complexes, membranes,
  micelles).
• High-end instrumentation, including NMR, light
  scattering, mass spec.
• Computer simulation methods for molecular
  modeling and analysis of complex data.

• Issues and Observations
• Integration as CBER high technology
• resource under review

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Laboratory of Bacterial Polysaccharides

• Areas of Research
• Characterization of immune responses to
  polysaccharide and conjugate vaccines
• Standardization of methods for relevant clinical
  application
• Development of novel physical and chemical
  methods for improved evaluation of licensed and
  experimental vaccines
• Characterization of innovative approaches to
  vaccine development, and evaluation of
  epidemiologic aspects of vaccine candidates

• Issues and Observations
• Polysaccharide immunology group added
• Mucosal immunity effort recommended
• Lab go-away to develop focus and
• transition strategy

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LABORATORY OF BACTERIAL TOXINS

• Areas of Research
• Neurotoxins Group
• Mechanism of toxin entry into nerve cells
• Interaction toxin with cellular components
• Mechanism of toxin persistence
• Corynebacteria Group
• Identification and characterization of iron
  regulated virulence factors in C. diphtheria
• Glycobiology Group
• Mechanism of bacterial capsular polysaccharide
  biosynthesis
• Binding of neurotoxins to glycolipid receptors

• Issues and Observations
• Development of neurotoxin assays
• Decreased emphasis on B. anthracis
• Increased emphasis on vaccine design

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Laboratory of Respiratory and Special Pathogens

• Areas of Research
• Bordetella pertussis, Bacillus anthracis, and
  Yersinia spp.
• Characterization of Virulence Factors and
• Studies on Mechanism of Action
• Studies on Regulation of Gene Expression
• Animal Models of Infection

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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

• Issues and Observations
• Malaria effort lacks investigator
• SVC recommended recruitment of MD
• with research background in human immune
• response to study correlations of human and
• animal responses

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Laboratory of Enteric and Sexually Transmitted
Diseases

• Areas of Research
• Invasion mechanisms of enteric pathogens
• Genetic regulation of bacterial virulence genes
• Mucosal immunity, dosing and adjuvants
• Anthrax and Shigella - Genetic analysis and
  development of live attenuated Salmonella-vectored
  vaccines

• Issues and Observations
• Mucosal Immunity group added
• STD work moved to LBP

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Laboratory of Immunobiochemistry

• Areas of Research
• Allergen structure and function
• Immunomodulation of allergic
• responses
• Chemokines and chemokine
• receptors in the modulation of
• immune responses

• Issues and Observations
• Cockroach allergen standardization
  collaboration with NIAID
• Increased attention to
• human T cell responses to allergens
• role of endotoxin in the safety and efficacy of
  allergen vaccines
• human antibody responses to cockroach allergens
• Decreased emphasis on
• latex allergens
• hymenoptera allergens

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Promotion Plan
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DBPAP Funding

• Salary and OVHD from FDA base
• Expendibles and Equipment
• General FDA Appropriation
• Division operating funds
• Special needs funds
• Per capita distribution of remainder evenly among
  staff involved
• CT Funds
• Handled similarly to general appropriation
• Divided among CT staff
• Extramural Funds
• Go directly to recipient
• Year End Funds

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Challenges and Realities Facing
Researcher/Reviewers

• Funding levels uncertain from year to year
  dependent upon appropriation process
• Bureaucratic hurdles
• Timing of workload determined by sponsor
  submissions, not by CBER

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Evaluation Components

• Review Individual
• Review Program
• Comment on Current and Future Directions

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DBPAP Program Focus Areas

• Standardization of Assay Methods for Bacterial,
  Parasitic and Allergenic Substances
• LMDQC, LB, LIB, LP, LESTD, LBT, LRSP, LMDCI
• Pertussis and Other Toxin-Mediated Diseases
• LMDQC, LB, LBT, LRSP
• Mycobacterial and Other Intracellular parasites
• LMDCI
• Mucosal Pathogenesis and Immunization
• LESTD
• Allergenic Products and Allergenic Diseases
• LB, LIB
• Products to Combat Bioterrorism Agents
• LMDQC, LB, LESTD, LBT, LRSP, LMDCI
• New Technologies for Characterization of
  Biologics
• LB

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Laboratory of Methods Development and Quality
Control

• Areas of Research
• Develop and evaluate
• Quality control methods for bacterial vaccines
• Serological methods for immune response
  measurement
• Animal models
• Gastrointestinal anthrax
• Bioassays for potency and toxicity

• Issues and Observations
• Recruiting for 1 position
• Lab Chief

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Bioterrorism Program

• Research/Review for
• B. anthracis
• F. tularensis
• Y. pestis
• Botulinum toxin
• Research Areas
• Genetic manipulation and regulation
• Virulence factors
• Vaccine improvement
• Immunologic assay standardization

Cutaneous anthrax
infection