National Center for Toxicological Research.

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	FY 2003 Actual	FY 2004 Enacted 1/	FY 2005 Estimate	Increase or Decrease
Total Program Level	$40,403,000	$39,652,000	$40,530,000	+$878,000
Center	$40,403,000	$39,652,000	$40,530,000	$878,000
FTE	226	233	227	-6
Budget Authority	$40,336,000	$39,652,000	$40,530,000	+ $878,000
Cost of Living-Pay 2/			$445,000	+$445,000
Food Defense -       Counterterrorism	$202,000	$164,000	$1,414,000	+$1,250,000
FTE			+1	+1
Administrative Efficiencies			-$817,000	-$817,000
FTE			- 7	- 7
Budget Authority FTE	226	233	227	-6
1/Contains a Budget Authority rescission of 0.59 percent for a total of $235,000 for NCTR. 2/Pay increases shown on separate line, and not reflected in individual initiative areas.

 

Historical Funding and FTE Levels

 

Fiscal Year	Program Level	Budget Authority	User Fees	Program Level FTE
2001 Actual	$36,248,000	$36,248,000	0	206
2002 Actual 3/	$39,259,000	$39,259,000	0	221
2003 Actual	$40,403,000	$40,403,000	0	226
2004 Enacted	$39,652,000	$39,652,000	0	233
2005 Estimate	$40,530,000	$40,530,000	0	227
3/ Includes FDA's FY 2002 appropriation and the Counterterrorism Supplemental.

 

MISSION

 

The mission of the National Center for Toxicological Research (NCTR) is to conduct peer-reviewed scientific research that supports and anticipates the FDA's current and future regulatory needs. This involves fundamental and applied research to define biological mechanisms of action underlying the toxicity of FDA-regulated products. This research provides the basis for the 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 with the aim to better understand 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 the FDA's pre-market application review and product safety assurance effort. The mission of NCTR is to:

• Conduct fundamental and applied research aimed at understanding critical biological events, such as adverse drug reactions and/or antibiotic resistance, to determine how people are adversely affected by exposure to products regulated by FDA;
• • 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 the Agency’s core activities of pre-market review and post-market surveillance;
• Develop methods to measure human exposure to products that have been adulterated or to assess effectiveness and/or the safety of a product; and,
• Provide the scientific findings used by the FDA product centers for pre-market application review and product safety assurance to the scientific community for the betterment of public health.

 

 

The NCTR conducts basic and applied research specifically designed to define biological mechanisms of action underlying the toxicity of FDA-regulated products.  This research is aimed at understanding critical biological events to the exposure of toxins and at developing methods to improve assessment of human exposure, susceptibility, and risk.  NCTR is co-located with the Office of Regulatory Affairs (ORA) Arkansas Regional Laboratory (ARL) which provides critical laboratory analysis for FDA-regulated products in a seventeen-state radius, on the campus of the Jefferson Laboratories of the FDA. All of the research performed at the National Center for Toxicological Research is targeted to fulfill three strategic research goals in support of FDA's public health mission:

• Risk Assessment for Regulated Products includes the development of new strategies and methods to test/predict toxicity and assess/detect risk for FDA regulated products, both new and on the market - this includes new genetic systems and computer-assisted toxicology for use in application review and development of gene chip and gene array technology;
• Knowledge Bases that Predict Human Toxicity requires the development of computer-based systems as knowledge bases, that predict human toxicity to enhance efficiency and effectiveness of premarket reviews; and,
• Methods for Use in FDA Standard Development and Product Risk Surveillance is the conduct of fundamental 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 Increases for FY 2005
By FDA Strategic Goal

 

FDA Strategic Goal	FY 2005 Increase Request	What the Increase Buys	Related Performance Goal(s)
Strong FDA		Maintain staffing levels and scientific capabilities that meet the demands of an increasing workload and new challenges, while facing the reality of a competing tight labor market.	Ensure that NCTR is able to continue to support the Agency's mission.
Protecting America from Terrorism	Food Defense -- CT --+$1,250,000	Research to facilitate the development of rapid, accurate tests to detect and monitor pathogenic microorganisms in food, food producing animals, and human intestinal microflora and to develop risk assessment models and techniques through the use of computational science; and, Upgrade and maintain laboratory capability to conduct research requiring BioSafety Level 3 containment in order to evaluate the effect of bioterrorism agents in the food supply.	Develop computer-based systems (knowledge base) that predict human toxicity to enhance the efficiency and effectiveness of pre-market product reviews.

 

Budget Authority

Cost of Living- Pay: + $445,000

 

FDA’s request for pay cost increases is essential to accomplishing its mission. Without a specially trained national cadre of scientific staff, FDA’s ability to adequately carry out the mission of protecting public health and providing consumer safety will be compromised. FDA must maintain staffing levels and scientific capabilities that meet the demands of an increasing workload and new challenges. Payroll costs, which account for over 60 percent of our total budget, significantly impact all FDA activities.

Without a specially trained national cadre of scientific staff, FDA's ability to adequately carry out the mission of protecting public health and providing consumer safety will be compromised. FDA must maintain staffing levels and scientific capabilities that meet the demands of an increasing workload and new challenges. Payroll costs, which account for over 60 percent of our total budget, significantly impact all FDA activities.

The total Agency request for pay increases is $14,352,000. NCTR's portion of this increase is $445,000. Without this, the FDA's ability to fulfill its mission to protect the public health by helping safe and effective products reach the market in a timely way, and monitoring products for continued safety after they are in use will be significantly reduced.

 

Food Defense - Counterterrorism:  + $1,250,000 and 1 FTE

 

FDA must uphold its responsibility for ensuring the safety of approximately 80 percent of the Nation’s food supply.  The possibility of food products being used as a vehicle for attack is particularly worrisome because such an event potentially affects everyone in the U.S.  To help build the capability to assess and then reduce risks associated with unexpected and potentially widespread health and safety threats, these resources would allow the FDA to invest in the protection of citizens by continuing to:

• Conduct applied research to facilitate the development of rapid, accurate tests to detect and monitor pathogenic microorganisms in food, food producing animals, and human intestinal microflora and to develop risk assessment models and techniques through the use of computational science; and,
• Upgrade and maintain laboratory capability to conduct research requiring BioSafety Level 3 containment in order to evaluate the effect of bioterrorism agents in the food supply.

 

Administrative Efficiencies:  - $817,000 and - 7 FTE

 

To fully embrace the President's Management Agenda, FDA is delayering its organizational structure, performing competitive sourcing reviews, modernizing its financial management system, and consolidating its information technology infrastructure. The National Center for Toxicological Research portion of these management improvements consists of -$817,000 and - 7 FTE.

 

PROGRAM ASSESSMENT RATING TOOL (PART)

 

In the FY 2004 review, FDA was assessed as five distinct programs (Foods, Human Drugs, Biologics, Veterinary Medicine, and Medical Devices and Radiological Health) and was rated as "results not demonstrated" due to a  lack of long-term outcome goals. To address this concern, long-term outcome goals were developed.

For FY 2005, the Office of Management and Budget conducted a second program review that treated FDA as a single agency program. In this review, FDA received a rating of "moderately effective" and score of 77 percent, up from 59 in FY 2004. This was due to considerable improvements in developing long-term agency-wide outcome goals that will demonstrate its effectiveness and impact on the public health. FDA also reduced the number of performance goals, and made various management improvements that further streamline its infrastructure while supporting core, mission-critical public health activities.

 

JUSTIFICATION OF BASE

 

EFFICIENT RISK MANAGEMENT: THE MOST PUBLIC HEALTH BANG FOR OUR REGULATORY BUCK

 

FDA will use science-based risk management in all Agency activities so that limited resources can provide the largest amount of health promotion and protection at the least cost for the public. Efficient risk management efforts for NCTR include:

• Applying new scientific discoveries in genomics, proteomics, metabonomics, and bioinformatics, new technologies that show promise in the mechanistic understanding of toxicological responses, to regulatory decision-making;
• Developing methods to measure human exposure to adulterated products and enhance the understanding of acute and chronic liver disease.  This research is used by FDA's product centers for premarket application review and product safety assurance to improve product quality and better predict the toxicity of new drugs; thereby, managing public health risk;
• Devising mechanistic models of risk for use by regulators in providing guidance to industry on allowable levels of mycotoxins in food products;
• Using microchip arrays -- small quantities of genetic material bound to computer chips -- to analyze a large number of chemical reactions, and provide diagnosis and treatment more  quickly.  This technique would allow doctors to screen their patients for genes that may cause adverse drug reactions, predict cancer susceptibility or determine a drug's effectiveness in controlling or curing an illness;
• Collaborating with FDA Centers, other Agencies and academia to develop a viable nutrition program to improve human health and evaluate the toxicity of botanical ingredients in dietary supplements.  These programs will promote research dealing with: chronic obesity in children, nutritional requirements in pregnant women, nutrition and its linkage to diabetes and the development of methods to predict the risk of poor nutrition on sub-populations at risk, such as the African-American community in the Mississippi Delta;
• Incorporating updated mathematical models into risk prediction models to more fully understand and predict the risk associated with foodborne bacterial exposure;
• Utilizing toxicoinformatics, the application of computer-assisted data management to the field of toxicology, to assess human risk; and,
• Using chemical probes to determine if bacteria in food, food producing animals or their environment have developed resistance to commonly used antibiotics.

 

Toxicant-Induced Exposure Studies are conducted to evaluate tissues and biological fluids for changes in metablolite levels that result from toxicant-induced exposure. This exposure could stem from adulteration of a product through the manufacturing process or as a result of a biological agent.

 

IMPROVING PATIENT AND CONSUMER SAFETY

 

Another important function of FDA is to identify risks associated with the use of medical products and reduce the occurrence of adverse events.  FDA provides the scientific findings used by FDA product centers for premarket application review and product safety assurance to the scientific community for the betterment of public health.  The Agency develops methods to manage or assess risk associated with products that have been adulterated, intentionally contaminated, or found to be detrimental to human health.  FDA will continue to: 

• Investigate the potential for photo-active chemicals found in cosmetics, foods or dietary supplements to increase the risk of cancer from solar radiation;
• Investigate the long-term consequences of using HIV therapeutics and endocrine disrupter products particularly from generation to generation; and,
• Develop animal models with genetic material from other species to better predict how animal study data relate to humans.

 

PROTECTING AMERICA FROM TERRORISM

 

FDA continues to monitor, evaluate, and follow up on the public health needs of new regulated products and to evaluate their use in counter terrorism preparedness and response.  These activities support the Department's goals to enhance the ability of the nation's health care system to effectively respond to bioterrorism and public health challenges.  FDA will continue to:

• Conduct fundamental applied research, including animal and microbial bioterrorism research and analytical studies aimed at understanding critical biological events to determine how people are adversely affected by exposure to FDA-regulated products and to develop a means by which potential biowarfare agents can be rapidly detected;
• Conduct research studies of bacterial strains in order to respond rapidly to various types of emergencies by supporting the rapid detection and identification of biological warfare agents or foodborne contaminants through methods developed in a state-of-the-art Biosafety Level-3 laboratory facility located in Jefferson, Arkansas; and,
• Devise methods to assess human risk associated with exposure to microbial agents that may be used by bioterrorists.

 

Translational Research Research performed by NCTR is "translational" -- meaning basic information derived from studies is further modified to apply to a specific question that is relevant to the FDA's public heath mission.  An example of this is the basic research developed to create a mutant mouse or rat.  FDA scientists use this technology and apply it to specific rodent strains to help assess the safety of a human or animal drug, or to understand the mechanism of action of a food additive medical device.  Studies include the nature, effects and detection of poisons and the treatment of poisonings--toxicology.

 

STRONG FDA

 

In support of the Agency's strategic goal to foster a strong FDA through scientific recruitments and administrative efficiencies, NCTR has increased its scientific expertise in the areas of computational science, food safety and counterterrorism by hiring additional expertise in these areas.  NCTR has also been an active participant in the development of the Shared Services Organization that will provide customer-centric administrative services agency-wide to provide administrative efficiencies.  To achieve this goal, NCTR is transferring approximately 50 percent of its administrative staff to shared services and is downsizing the remaining administrative staff by 13 percent.

A strong FDA will ensure a world-class professional workforce, effective and efficient operations, and adequate resources to accomplish the mission of FDA.  FDA will continue to:

• Recruit, reward and retain state-of-the-art scientists and health professionals and utilize web-based recruiting strategies to broaden reach and accelerate access;
• Increase the use of existing formal and informal training programs such as intern programs and mentorship experiences to train and develop a highly skilled workforce;
• Assure that scientists maintain state-of-the-art expertise by training them in emerging technologies;
• Expand mentoring programs for different stages in an employee's life cycle including:  programs to assimilate new employees quickly; programs for career progression, targeted career tracks tailored for reviewers, compliance officers, investigators and administrative staff; and programs to identify future leaders early and facilitate leadership development; and,
• Support the President's Management Agenda and the Agency's competitive sourcing A-76 effort by performing cost comparison studies for commercially identified functions.

 

EFFICIENT RISK MANAGEMENT: THE MOST PUBLIC HEALTH BANG FOR OUR REGULATORY BUCK

Toxicological Research

 

• Conducted studies that demonstrate the potential utility of new DNA technology in evaluating the mechanisms by which chemicals exert their toxicity using test methods that sift through and analyze information contained within a set of chromosomes;
• Established a link between toxicology and data management at the FDA, utilizing online technology that includes data storage in the secure NCTR-developed database, ArrayTrack, for interpretation of data received from DNA chromosome test studies for use by the human drugs and foods programs; and,
• Completed studies to determine carcinogenicity of therapeutic agents used in aquaculture, and on the potential human carcinogen, acrylamide, found in fried foods such as french fries, potato chips, crackers and breakfast cereals emphasizing dose-response relationships and the development of biomarkers for assessing exposure; and continued studies of nutritional folic acid deficiency and tumor progression in newborns.

 

Minority Health

 

• Conducted cost effective multigeneration studies of genistein and ethinyl estadiol with NIH to demonstrate both early and long term effects of these agents on bone density and strength at dose levels that are of relevance to human exposures; Continued genomics research that provides new knowledge on the identification of subpopulations that are more susceptible to chemical carcinogens and those likely to experience adverse drug reactions or decrease therapeutic drug efficacy; and,
• Investigated the causes of human cancers of the colon/rectum, pancreas, esophagus, breast, prostate, lung, and bone marrow in Africa-Americans and Caucasians to bring about greater representation in clinical trials.

 

Antimicrobial Resistance

 

Researchers continue to conduct studies that determine whether antimicrobial resistance occurs in bacteria isolated from animal feeds containing antibiotics, the pattern of resistance development in bacteria found in animals fed antibiotics, and differences in survival rates of drug-resistant pathogens compared to non-resistant pathogens; and, Microbiological experiments were conducted that suggest a technique to reduce or eliminate contamination of the environment in agricultural uses of clinically important antibiotic drugs.

 

Antimicrobial Resistance Antimicrobial resistance is the ability of a microorganism to withstand an antimicrobial agent, typically, bacteria found in animals fed antibiotics. Tests are conducted of substances that promotes the growth of microorganisms and of inherent pathogens -- disease-causing agents, such as viruses and bacteria.

 

EMPOWERING CONSUMERS: IMPROVING HEALTH THROUGH BETTER INFORMATION

 

• ·Expanded readership of the "Regulatory Research Perspectives", an online journal with articles on the potential relationship between methyl group deficiencies and pathologies such as cancer, birth defects, and neurotoxicity.  This journal is a vehicle for all FDA scientists to share research advances; and,
• Promoted the Agency's outreach program by disbursing information to the general public via informational tools including the annual NCTR Research Accomplishments and Plans document, NCTR Web Page, One-Pager, NCTR Quarter Page, Center-Wide newsletter, community impact flash presentations, and various presentations at scientific conferences and symposia.

Dietary Supplements

• Continued studies to understand how toxins in chemicals, food additives, and biological therapies, may induce birth defects.  This research supports the theory that diet may play a role in the development of normal offspring and interactions between diet and toxicants may be important in producing certain birth defects; and,
• Collaborated with and provided guidance to NIH on the alkaloid content of Ephedra sinica, a dietary supplement in widespread use recognized as a health hazard, particularly as used by athletes.

 

Cosmetics

 

• Measured the effect of cosmetic ingredients on sunlight-induced skin cancer, and the stability and toxicity of tattoo ink ingredients.  These studies are conducted in the FDA's unique state-of-the-art phototoxicology facilities at NCTR.  The studies on the tattoo ingredients are new and timely, given the large numbers of young Americans receiving tattoos; and,
• Assessed the safety of hair dyes especially those with frequent use that have been linked to the increased the risk of developing bladder cancer.

 

Women's Health

 

• Studied the effectiveness of anti-retroviral drugs used to prevent the mother-to-child transmission of human immunodeficiency virus type 1, the virus responsible for acquired immunodeficiency syndrome. FDA conducted a series of investigations to examine the long-term consequences of exposure on the mothers, feti and newborns to these drugs; and,
• Conducted experiments to understand the mechanisms for tumor induction and increased risk of endometrial cancer in women with emphasis on DNA adducts formed from the drug tamoxifen used in the treatment of breast cancer.
• Continued research program to assist the Agency in non-clinical and clinical drug safety assessment and drug producing issues by studying the metabolic changes in bio-fluids caused by drugs, analgesics, and herbal products to determine health effects; and,
• Performed on a variety of behavioral tests that measure timing ability, memory, and if learning is different between persons with mild to moderate Alzheimer's Disease and persons who have no diagnosis of the disease.

 

NCTR's Support Of Over-The-Counter Drug Activities Over-the-counter drugs, such as benzodiazepines and antihistamines, offer severe regulatory concern because they are known to cause liver tumors in rodents.  A collaborative project between the Biochemical and Molecular Markers of Cancer Program and the Transgenics Program at the NCTR may eventually result in developing a new-generation bioassay for FDA-regulated chemicals.

 

Children's Health

 

• Assessed the potential public health risk associated with the use of anesthetic agents that are known to interact with the neuro-receptor systems of children which has become a growing health concern, particularly as affected in combination with drugs and other environmental agents; and,
• Collaborated with the University of Arkansas for Medical Science Continued to study if children with major depression according to the Diagnostic and Statistical Mental Disorders criteria perform differently than children without such a diagnosis on tests of motivation, simple visual discrimination, timing ability, memory and learning.  This is the first study that proposes to examine performance on a variety of operant behavioral tasks that measure complex brain functions in pre-adolescent children diagnosed with major depression.   Having a defined behavioral baseline will assist FDA in developing therapies for children.

 

Nutrition

 

• Studied the impact of dietary restrictions and the positive effects for the overall health.  These types of studies increase the knowledge of how calories modify the mechanism underlying cancer development in humans and reducing the incidence of these diseases.

 

PROTECTING AMERICA FROM TERRORISM

 

• Developed a computational counter-terrorism method to rapidly detect biological pathogens and to correctly identify bioterror agents;
• Developed, in collaboration with the Arkansas Regional Laboratory, a method for microbial isolation that dramatically reduces analysis time of contaminated food to only a few hours vs. 2-3 days.;
• Continued collaborations through the established Interagency Agreement with the Federal Aviation Administration to expand the decomposition gas release methodology to detect explosives in airline cargo;
• Shared expertise and laboratory infrastructure to prevent or minimize threats from counterterrorism through a Memorandum of Agreement with the Arkansas Department of Health; and,
• Completed construction of a Biosafety Level-3 facility which will provide high containment rooms for use by the Arkansas Regional Laboratory, ORA's Laboratory in the Southwest Region, and surge capacity for the State of Arkansas Department of Health.  The contract has been awarded to construct the BSL-3 facility, which should be available for use in early 2004.

 

 

Program Output	FY 2003 Actuals	FY 2004 Estimate	FY 2005 Estimate
Research Publications	168	175	175
Scientific Presentations	213	220	220
Patents (Industry)	5	5	5
Interagency Agreements	4	4	4
Cooperative Research & Development Agreements	3	5	5
Total Ongoing Research Projects	219	220	220

 

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