Division of Bacterial, Parasitic and Allergenic Products

OVRR/CBER/FDA

Laboratory Mission and Functions

• Research

• Review

• Post-licensure surveillance

– Inspection/compliance

– Lot release testing/protocol review

– Label/promotional activity review

• Consultations with outside organizations

Assure Safe and Effective Products for ImmunologicalControl of Bacterial, Parasitic and Allergenic Agents Affecting Human Health

DBPAP Role in Regulatory Review and Approval

Pre-IND IND License

•Meeting withsponsors toprovide guid-ance

•Rev. of orig. Submission &all subsequentammendments

•Tech. Advice forproduct and assay development

•Rev. product manf.data & determin-ation of prod. specs.

•Meet with sponsors

•Present prod. ToAdvisory Comm.

•Meet with spon-sors

•Eval. Assays to measure clinicalresponse to prod.

•Eval. product characterizationmethods & assays

•Rev. of final prod.manuf. process, in-cluding in process& final product specs.

•Est. lot release protocolsfor CBER productrelease

•Conduct pre-approvalinspection of thefacility

DBPAP Role in Regulatory Review and Approval

Pre-IND IND License Post Licensure

•Review of Biological Deviationreports from industry

•Participation in biannual inspections of licensed products

•Review of post approval commitments

•Review of subsequent supplementsfor changes to maufacture oradditional indications

•Meet with sponsors

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

•

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

Division of Bacterial, Parasitic and Allergenic Products (DBPAP)

Laboratory of ImmunobiochemistryJay Slater, M.D.-Chief

Immediate Office of the Director

Richard Walker, Ph.D.-DirectorDeputy Director

Regulatory Staff Administrative Staff

Laboratory of Methods Development andQuality Control

Bruce Meade, Ph.D.-Chief

Laboratory of Respiratory and Special Pathogens

Drusilla Burns, Ph.D.-Chief

Laboratory of Bacterial Polysaccharides

Carl Frasch, Ph.D.-Chief

Laboratory of Enteric and Sexually Transmitted Diseases

Dennis Kopecko, Ph.D.-Chief

Laboratory of Mycobacterial Diseases and Cellular Immunology

Sheldon Morris, Ph.D.-Chief

Laboratory of Bacterial Toxins

Willie Vann, Ph.D.-Chief

Laboratory of BiophysicsRichard Pastor, Ph.D.-Chief

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

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

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

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)

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

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

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 combinationTB DNA vaccine

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

Laboratory of Immunobiochemistry

Areas of Research

• Allergen structure and function

• Immunomodulation of allergic

responses

• Chemokines and chemokine

receptors in the modulation of

immune responses•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

Recent Milestones

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

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