Department of Health and Human Services
Food and Drug Administration
Fiscal Year 2005
NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH
|
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.
BACKGROUND
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.
National Center for Toxicological Research Program Activity Data
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 |