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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New or Improved Products Possible in the Next Ten
Years

• Respiratory Pathogens
• Streptococcus pneumoniae
• Mycobacterium tuberculosis
• Pseudomonas aeruginosa
• Neisseria meningitidis A,B,C
• 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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New or Improved Products Possible in the Next Ten
Years

• 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
• Coccoidian
• Leishmania

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Division of Bacterial, Parasitic and Allergenic
Products (DBPAP)
Laboratory of Respiratory and Special
Pathogens Drusilla Burns, Ph.D.-Chief
Laboratory of Immunobiochemistry Jay Slater,
M.D.-Chief
Immediate Office of the Director Richard Walker,
Ph.D.-Director Deputy Director Regulatory Staff
Administrative Staff
Laboratory of Bacterial Toxins Willie Vann,
Ph.D.-Chief
Laboratory of Biophysics Richard Pastor,
Ph.D.-Chief
Laboratory of Mycobacterial Diseases and
Cellular Immunology Sheldon Morris, Ph.D.-Chief
Laboratory of Enteric and Sexually Transmitted
Diseases Dennis Kopecko, Ph.D.-Chief
Laboratory of Methods Development and Quality
Control Bruce Meade, Ph.D.-Chief
Laboratory of Bacterial Polysaccharides Carl
Frasch, Ph.D.-Chief
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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

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Laboratory of Methods Development and Quality
Control

• Areas of Research
• Develop, standardize, and evaluate quality
  control methods for bacterial vaccines
• Develop, evaluate, and apply serological methods
  to measure immune response in vaccine trials
• Coordinate quality assurance activities within
  DBPAP and provide leadership in initiative to
  accredit CBER quality control testing
  laboratories

• Recent Milestones
• Developed QC methods incorporated into WHO
• acellular pertussis vaccines guidelines
• Leader effort to standardize pertussis
  immunoassays
• 9 publications evaluating safety and
  immunogenicity
• of acellular pertussis vaccines

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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

• Recent Milestones
• Licensure of pneumococcal conjugate vaccine
• Genetic typing method for gonococcal epidemiology
• Discovered conjugation modifies epitopes in
• polysaccharide vaccine conjugates

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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.

• Recent Milestones
• Simulation of aquaporin in membrane
• NMR based 3-D structure determination of
  carbohydrates and of peptides in micelles
• Synthesis of multiple antigen peptide (MAP)

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Laboratory of Respiratory and Special Pathogens

• Areas of Research
• Structure/Function Studies of Toxins
• Regulation of Virulence Factors of
• B. pertussis and B. anthracis
• Animal Models of B. pertussis Infection

• Recent Milestones
• Led the effort to license acellular
• pertussis vaccines

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Laboratory of Bacterial Toxins

• Areas of Research
• Characterization of Tetanus Toxin Structure and
  Function
• Characterization of Iron-Related Virulence
  Determinants in C. diphtheriae and B. anthracis
• Biosynthesis of bacterial polysaccharides
  polysialic acids of E. coli and hyaluronic acid
  of B. anthracis

• Recent Milestones
• Licensure of Botulinum type B for cervical
  dystonia
• Discovery of Heme oxygenase in C. diphtheriae

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The Laboratory of Mycobacterial Diseases and
Cellular Immunology

• Areas of Research
• Evaluation of protective immune responses to
  intracellular bacteria
• Assessment of DNA vaccination strategies against
  tuberculosis
• Characterization of a unique family of
  tuberculosis proteins

• Recent Milestones
• Licensure of the Lyme Vaccine
• Development of an effective combination
• TB DNA vaccine

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Laboratory of Enterics and Sexually Transmitted
Diseases

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

• Recent Milestones
• Defined host and bacterial requirements
• Novel MT-dependent C. jejuni invasion system
• Defined DNA sites and transcriptional activator
  residues involved in virulence gene regulation

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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

Recent Milestones

• Development of a provisional US standard for
  latex
• Isolation and characterization of latex allergen
  Hev b 5
• Grass pollen allergen extract standardization
• Re-validation of competition ELISA to determine
• potency of grass mite allergen extracts
• Statistical basis for assignment of release
  limits
• for standardized allergens
• Criteria for prioritization of allergens for
  standardization

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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
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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