NCTR Overview

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NCTR Overview

• Daniel A. Casciano, Ph.D.
• National Center for
• Toxicological Research

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Organization of Presentation

• Some information on FDA
• Organization of the NCTR
• Function of SAB

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Department of Health and Human ServicesFood and
Drug Administration
Office of the CommissionerCommissioner of Food
and Drugs
Office of the Chief Counsel
Office of Equal Opportunity
Office of the Administrative Law Judge
Office of the Senior Associate Commissioner
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Center for Drug Evaluation and Research

• MISSION The Center assures that safe and
  effective drugs are available to the American
  people.
• ISSUES Prescription Drug User Fee Act (PDUFA),
  Adverse Events Reporting, Gene Therapy,
  Monitoring Drug Information and Advertising, Drug
  Quality, Drug Safety

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Center for Food Safety and Applied Nutrition

• MISSION The Center is responsible for promoting
  and protecting the publics health and economic
  interest by ensuring that the nations food
  supply is safe, sanitary, wholesome, and honestly
  labeled. The program also ensures that cosmetic
  products are safe and properly labeled.
• ISSUES Food Safety, Joint Institute for Food
  Safety and Applied Nutrition, Dietary
  Supplements, Food Labeling, Seafood
  Decomposition, Phototoxicity(a Hydroxy acids)

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Center for Veterinary Medicine

• MISSION CVM is responsible for ensuring that
  animal drugs and medicated feeds are safe and
  effective for their intended uses and that food
  from treated animals is safe for human
  consumption.
• ISSUES Food Safety, Antibiotic Resistance,
  Aquaculture.

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Center for Devices and Radiological Health

• MISSION The mission of CDRH is to protect the
  public health by providing reasonable assurance
  of the safety and effectiveness of medical
  devices and by eliminating unnecessary human
  exposure to radiation emitted from electronic
  products (medical, industrial, and consumer).
• ISSUES Reuse of Single-Use Medical Devices,
  Medical Device Surveillance, Medical Errors,
  Regulations, FDAMA, Reengineering, Device GMP
  Inspections, Tissue-Based Products (BSE/TSE),
  Genetic Assay Kits, People Scanners (X-Rays),
  Ultrasound, Electro-magnetic Radiation

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Center for Biologics Evaluation and Research

• MISSION The mission of CBER is to protect and
  enhance the public health through regulation of
  biological and related products including blood,
  vaccines, therapeutics and related drugs and
  devices according to statutory authorities.
• ISSUES Biologic Review Actions, Major Drug
  Approvals, Vaccine Approvals, Bioterrorism,
  Research in Proteomics, Compliance Activities,
  Action Plans (Blood, Tissue, Devices),
  Xenotransplantation

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Office of Regulatory Affairs

• MISSION The Office of Regulatory Affairs (ORA)
  is the lead office for all Field activities of
  the Food and Drug Administration.
• ISSUES International Harmonization, Imports,
  Leveraging (EPA, States), Seafood and Dairy
  Exports, Laboratory Information Bulletins,
  Research, Bioresearch Monitoring Program (BIMO),
  Adverse Action Reports (All Centers), Recalls,
  Seafood Decomposition, Bacterial Contamination

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DEPARTMENT OF HEALTH AND HUMAN SERVICESFOOD AND
DRUG ADMINISTRATIONNATIONAL CENTER FOR
TOXICOLOGICAL RESEARCH
Office of the Director
Office of Research
Office of Management
Division of Biochemical
Division of Genetic
Office of Management
Office of Planning,
Toxicology
and Reproductive
Services
Finance, and
Toxicology
Information Technology
Division of Biometry
Division of Microbiology
Division of Facilities,
Division of Planning
and Risk Assessment
Engineering and
Maintenance
Division of Chemistry
Division of
Division of
Division of Financial
Neurotoxicology
Administrative
Management
Services
Division of Veterinary
Division of Molecular
Division of
Services
Epidemiology
Information
Technology
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Division of Microbiology
National Center for Toxicological Research Food
and Drug Administration Jefferson, Arkansas
Carl E. Cerniglia, Ph.D. Director
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DIVISION OF MOLECULAR EPIDEMIOLOGYOVERVIEW

• Fred F. Kadlubar, Ph.D.
• Director

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Division ofBiochemical Toxicology

• Frederick A. Beland, Ph.D.
• Director

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Division of Genetic and Reproductive Toxicology

• Martha M. Moore, Ph.D.
• Director

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Division of Neurotoxicology

• William Slikker, Jr., Ph.D.
• Director

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Division of Biometry and Risk Assessment

• Ralph L. Kodell, Ph.D.
• Director

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Division of Chemistry

• Robert J. Turesky, Ph.D.
• Director

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Division of Veterinary Services

• William M. Witt, D.V.M., Ph.D.
• Director

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FDA/NCTR/NIEHS Interagency Agreement

• William T. Allaben, Ph.D.

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NCTR RESOURCESFDA Allocation
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FTE ALLOCATION
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NCTR RESOURCES
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Out-year Budget RequestsFY2002
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Out-year Budget RequestsFY2003

• Premarket Review Proteomics, Genomics, Gene
  Chip, Microarray and Bioinformatics to Support
  and Guide Premarket Review (2,646,000)
• Antimicrobial Resistance (500,000)
• Dietary Supplements (500,000)
• Food Safety (12,000,000)
• Cost of Living (2,953,000)

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What Do We Do For FDA?

• NTP Bioassay
• Food Safety Initiative
• Fresh Tag
• Bioterrorism
• Intellectual Resource

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Fundamental Research

• DNA adduct
• Artificial GI tract
• Estrogen and computational toxicology
• Nutrition (PCR)
• Transgenic animals
• Risk Assessment procedures
• Operant behavior
• Toxicogenomics, Proteomics

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Function of SAB

• Advise NCTR Director on science, budget and other
  issues (NCSS subcommittee)
• Members serve on full SAB for review of
  site-visit reports
• Members serve as chair and/or committee member of
  program/division site-visit teams

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Toxicology in the Next Millenium
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Toxicology Data Continuum
Protein Modification
Adaptation, repair or damage
Gene expression
Protein synthesis
Dysfxn
TOXICITY!
D
functional Activity
Biochemical Mechanism
Proteomic
Genomic
Cellular
Organism
Tissue/Organ
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Better Predictive Tests

• DNA- and protein-based technologies
• Transgenics
• Biomarkers (rodent/human homologues)
• Alternative to animals
• Computational Science

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Current Genomics Project at the NCTR

• Human genotyping
• Gene expression profiles

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NCTR Gene Expression Microarray Project
Effects of Chemical Toxicants on Gene Expression
Profiles

• Expose rat cells in primary culture to a variety
  of toxicants evaluate gene expression.
• Expose intact animal to same toxicants evaluate
  gene expression in interested organ.
• Expose human cells in primary culture to same
  toxicants evaluate gene expression.
• Predict in vivo human response.

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Development of SNP-Chips

• High throughput genotyping using DNA microarray
  technology will be used to allow facile genetic
  screening of human populations for
• Adverse Drug Reactions
• Cancer Susceptibility, Early Diagnosis
• Recurrence
• Drug Efficacy in Subsets of the Population
• Individualized Drug Dosing Rapid
  screening for variant genes involved in
  metabolism, DNA repair, and cellular homeostasis
  should allow the selection of genetically
  heterogeneous groups for inclusion in clinical
  trials and thereby increase our ability to
  protect public health in a diverse population.

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Developing Proteomics
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Problems

• Commercial vs. In-house development of chips
• Toxicogenomics staffing

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Some Solutions

• Creative recruitment (Cellular and Molecular
  Toxicology Group)
• Leveraging
• Collaboration
• IPA

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Toxicology Data Continuum
Protein Modification
Adaptation, repair or damage
Gene expression
Protein synthesis
Dysfxn
TOXICITY!
D
functional Activity
Biochemical Mechanism
Proteomic
Genomic
Cellular
Organism
Tissue/Organ