National Center for Toxicological Research

1/ Includes Salaries & Expenses, Rent, and PDUFA, where applicable.

EXPLANATION OF PROGRAM

NCTR is co-located with the Office of Regulatory Affairs (ORA) Arkansas Regional Laboratory (ARL), on the campus of the Jefferson Laboratories of the FDA. The mission of the National Center for Toxicological Research (NCTR) is to conduct peer-reviewed scientific research that provides the basis for FDA to make sound science-based regulatory decisions, and to promote the health of the American people through its core activities of premarket review and postmarket surveillance. This involves fundamental and applied research specifically designed to define biological mechanisms of action underlying the toxicity of products regulated by FDA. This research is aimed at understanding critical biological events in the expression of toxicity and at developing methods to improve assessment of human exposure, susceptibility and risk and apply these scientific findings to FDA's pre-market application review and product safety assurance effort.

FY 2001 BUDGET REQUEST

ASSURING SAFETY/STRENGTHENING SCIENCE INITIATIVES

PREMARKET INITIATIVES + $0.5 MILLION, 2 FTE

Bringing Products of New Technology to Market +$ 0.5 million, 2 FTE

Limited scientific knowledge delays health and safety benefits and may lead to over-regulation because of inadequate understanding of the risks involved. Requested resources will be used to improve the premarket process through:

• Support the premarket review process by conducting biologically based mechanistic studies combined with predictive modeling to provide better knowledge of individually targeted risk. Leverage resources from FDA stakeholders by employing new predictive modeling systems that combine to provide data essential to reducing cancer risk in clinical trials developed in partnership with industry (Chemical Manufactures Association [CMA] and Genometrix) and government (EPA). Failure to conduct mechanistic studies will require that risk continue to be regulated by costly, time-consuming animal bioassays. (NCTR Performance Goal # 2)
• Assess the safety of foods derived from genetically modified organisms (GMO) in collaboration with FDA's Center for Food Safety and Applied Nutrition (CFSAN) and Center for Veterinary Medicine (CVM). The import/export market is currently being challenged by the lack of credible scientific data on the safety of GMOs. This research will address this critical need and provide data to relieve public concern.

SPECIAL PROGRAM INITIATIVES

Food Safety Initiative + $2.0 million, 3 FTE

FY 2001 will mark the fourth year of a highly successful multi-agency initiative to control and reduce foodborne pathogens in the American food supply. The benefits of this investment are evidenced by the fact that the time it takes to respond to numerous outbreaks have been shortened, resulting in fewer potential deaths and illnesses to American consumers.

In FY 2001, FDA will further strengthen and enhance Federal, State and local food safety systems through the use of uniform minimum standards and practices for inspections and consistent enforcement. In collaboration with its sister agencies, the FDA will conduct the following activities to improve inspectional coverage and related research efforts.

Develop methods to predict more quickly and accurately risks associated with antimicrobial resistance and foodborne pathogens/contaminants. Examples include:

• Expand support and expertise, in partnership with the CFSAN, in molecular methods that can be used to rapidly identify markers of toxicity of food borne pathogens. This objective is necessary to adapt new technology for monitoring the safety of our food supply.
• Develop new methods, with the CVM, for routine surveillance of fluoroquinolone resistant Salmonella and Campylobacter to provide the data needed to make informed risk decisions concerning the use of quinolone-based antimicrobials in poultry production and food borne antibiotic resistance. Increased incidence of antibiotic risk in the food supply may compromise the use of antibiotics to combat human disease.
• Apply risk assessment methodology to microbial contamination and antibiotic resistance. If these methods are not developed, our ability to adequately predict pathogenic risk will jeopardize public safety. (NCTR Performance Goal # 5)

Countering Bioterrorism +$ 1.0 million, 1 FTE

FDA plays a critical role in the preparation for bioterrorist attacks by reviewing products to counter the effects of anthrax and other potential bioterrorism events. The Agency must also conduct Good Manufacturing Practice inspections of manufacturers whose products may be stockpiled as a part of the government's bioterrorist efforts. As part of the interagency effort FDA intends to:

• Expand the mass spectrometry-based approaches to identify biomarkers of toxicity associated with biological warfare agents. This technique will significantly reduce the danger associated with terroristic threats. (NCTR Performance Goal # 6)
• Develop novel techniques to identify new bacteriological and chemical contaminants in the food supply. These techniques can crossover to provide methods of assessment for potential biochemical terrorist capabilities. Maintaining currency in analytical techniques will ensure the American public has the best and most accurate tools to fight food borne disease as well as identify biological warfare agents.

JUSTIFICATION OF BASE

The National Center for Toxicological Research (NCTR) conducts FDA mission-critical, peer-reviewed research that is targeted to develop a more scientifically sound basis for regulatory decisions and reduce risks associated with FDA-regulated products to protect, promote, and enhance Americas public health. Specific aims of NCTR's research are:

• To develop new strategies, methods, and systems to predict toxicity that anticipate new product technology in order to support FDA's commitment to bring this technology to the market rapidly.
• To understand mechanisms of toxicity and design better risk assessment/detection techniques and methods for use in pre-market review and product and health surveillance.  
• The NCTR provides the Agency with a high-quality, cost-effective, health science research program, which results in the application of new scientific knowledge through leveraging of research findings from NIH and academia, enhancing the FDA's regulatory practices.

NCTR's strategic research goals support the FDA's mission to bring safe and efficacious products to the market rapidly and to reduce the risks of products on the market. NCTR's strategic goals are as follows:

• Develop new strategies and methods to test/predict toxicity and assess/detect risk for FDA regulated products (new and those already on the market)
• Develop computer-based systems (knowledge bases) that predict human toxicity to enhance the efficiency and effectiveness of pre-market product reviews.
• Conduct research to understand mechanisms of toxicity, assess new product technology and provide methods for use in FDA standards development and product risk surveillance.

National Center for Toxicological Research

Selected FY 1999 Accomplishments

• Conducted research into areas that are most pertinent to FDA needs. Organizational and operational changes were made to improve our effectiveness and efficiency. Divisions have been consolidated to develop more intellectual synergy and to optimize research capabilities. 
• Constructed a state-of-the-art phototoxicity facility to evaluate the toxic interactions between drugs or cosmetics and exposure to sunlight.

Developed new strategies for the prediction of toxicity

Developed transgenic models that can be used to screen for toxicities and better understanding mechanisms of toxicity. The models are constructed so that easily measured reporter genes can be inserted into rodent models. By using this transgenic technology, scientists are learning more and more about how specific chemicals cause toxicity in humans. For example, the data generated in the transgenics program are used to study human disease processes to better understand cross-species extrapolation.

Developed Endocrine Disrupter Knowledge Bases (EDKB)

• Completed a system provides an Internet-accessible, virtual environment where researchers can share pertinent research citations, data and predictive models. During the programs first year, several computational chemistry methodologies were evaluated and found to yield statistically robust correlations for predicting estrogenicity. The FDA Office of Women's Health provided partial support for this work. This knowledge base is a prototype that will assist in risk and regulatory decisions for compounds that may alter estrogen responses and disrupt human endocrine systems. 
• Customized the system to support the evaluation of thirty-six chemicals for estrogenicity for the Center for Food Safety and Applied Nutrition (CFSAN) and the Center for Drug Evaluation and Research (CDER).

Method-, Agent-, and Concept-Driven Research

Explored new, innovative approaches to better predict human risks from the existing rodent bioassay data. When complete, these data will be used by the FDA to accurately set exposure limits for various products.

Food Safety Initiative (FSI)

• In collaboration with the CFSAN, CVM, and as part of the FSI, the NCTR, developed methods to identify markers of foodborne pathogens and to assess whether these microorganisms undergo change, thus becoming more virulent. 
• Developed an indicator of seafood decomposition known as Fresh Tag^TM licensed by Cox Recorders of Belmont, SC.  
• Developed methods and built biologically based dose-response models of microbial infection to assess survival, growth, and infectious components of microbial risk to address the question of human risk from foodborne pathogens. This research capitalizes on partnerships with USDA.

Laboratory Consolidation at the Jefferson Laboratories of the FDA

Continued construction of the Arkansas Regional Laboratory. This facility, once completed, will enhance the science base and ensure the efficient use of FDA facilities, providing for effective intra-center collaborations on scientific issues critical to the Agency and the American public. The construction of the Arkansas Regional Laboratory (ARL) will ultimately save FDA millions of dollars due to consolidation of equipment, staff, utilities and support.

Program Activity Data

*One IAG includes 22 separate projects

Note: The decrease in program activity within the strategic goals from FY 2000 to FY 2001 is due to shifting the focus of NCTR's research to toxicity prediction, an area critical to FDA's pre-market review. This shift addresses the Commissioners priorities more effectively.

Edited 3/1/2000