Report to the Nation: 2003
Center for Drug Evaluation and
Food and Drug Administration
U.S. Department of Health and Human Services
CDER 2003 Report to the Nation:
Improving Public Health Through Human Drugs
version of this document
Last year, we at the Center for Drug Evaluation and
Research worked hard to meet the challenge of promoting and
protecting the public health. We were pleased to welcome our
new colleagues involved in the review of therapeutic
biologics. The dedication, creativity and expertise of all
our professional staff have enabled us to meet our everyday
deadlines and embark on new initiatives under the framework
of FDA’s strategic plan. The strategic plan is very
familiar to us because it builds on what we have been doing.
The plan outlines a very ambitious effort to achieve five
broad priority goals.
Efficient, science-based risk management
We have long led the world in applying the principles of
risk management-assessing public health risks, analyzing
methods for reducing them and taking appropriate action.
With the expanding complexity of our medical challenges and
the need to reduce the health risks facing the public at the
lowest cost to society, efficient risk management is more
important than ever.
Our approach to efficient risk management requires the
use of the most current biomedical, statistical, managerial
and economic science. We aim to achieve quicker access to
safe and effective new products and reduce public health
risks without unnecessary costs by:
- Identifying scientific research gaps along the
critical path to drug approval.
- Employing principles and technologies that can reduce
avoidable delays and costs in product approvals.
- Overhauling and updating the way medical products are
- Implementing an enforcement strategy that combines
clear communications to industry backed up by effective
civil and criminal enforcement.
Patient and consumer safety
Too many Americans suffer from preventable adverse events
related to pharmaceutical products resulting in human
suffering and avoidable medical costs. Consequently, we are
enhancing our post-market monitoring, communication and
In addition, one of the most promising new ways we can
improve the system for reporting safety problems is to have
direct and secure access to relevant modern electronic
health information. By supplementing the current passive
reporting systems and partnering with healthcare providers
and other government agencies, we will develop more
innovative and effective information on the risks associated
with regulated products.
We will help speed the implementation of safer systems
for medical care through steps such as:
- Bar coding medications in hospitals.
- Implementing 21st-century methods for communicating
with health professionals to reduce adverse events.
- Improving our current system for colleting and acting
on adverse events related to the products we regulate.
Better informed consumers
Informed consumers represent our nation’s greatest
public health asset, because the choices Americans make
every day can have a great impact on their own health and
the health of the nation.
We are undertaking major new efforts to ensure consumers
have the most up-to-date, truthful information on the
benefits and risks of regulated products. In this arena, we
meet two complementary objectives:
- Ensure the information that sponsors provide about
prescription drug products is accurate and allows for
their safe use.
- Communicate directly with the public concerning
benefits and risks of the products we regulate.
Our goal is a well-informed public, empowered to make
better choices to improve their health.
We are working harder and more creatively than ever to
speed the availability of the next generation of safer, more
effective countermeasures to protect Americans from
biological, chemical, nuclear and radiological agents of
terrorism. We have two complementary-but necessarily
separate-roles in this effort:
We will help get products developed.
We will then review marketing approval data on the same
A strong FDA
Our continued ability to carry out our mission of
protecting and advancing America’s health rests squarely
on our most important resource: a talented and dedicated
staff. More than ever, we rely on a solid cadre of
experienced physicians, toxicologists, chemists,
statisticians, mathematicians, project managers and other
highly qualified and dedicated professionals. The expertise
of our professional staff is essential for making our
regulatory decisions balanced and fair. A committee of our
scientists oversees an extensive program of training,
seminars, case study rounds and guest lectures that helps
keep our scientists up-to-date on the latest developments in
their disciplines and current industry practices.
As we look to the challenges ahead, we remain steadfast
in our commitment to facilitate the availability of safe and
effective drugs, keep unsafe or ineffective drugs off the
market, improve the health of Americans and provide clear
and easily understandable drug information to health
professionals, patients and consumers.
|Janet Woodcock, M.D.
Director, January-September 2003
Center for Drug Evaluation and Research
Acting Deputy Commissioner for Operations
Food and Drug Administration
|Steven Galson, M.D., MPH
Center for Drug Evaluation and Research
Who we are
The Center for Drug Evaluation and Research is America’s
consumer watchdog for medicine. We are part of one of the
nation’s oldest consumer protection agencies-the Food and
Drug Administration. The FDA is an agency of the federal
government’s Department of Health and Human Services. We
are the largest of FDA’s five centers, with about 1,800
employees. Approximately half of us are physicians or other
kinds of scientists. Many of us have experience and
education in such fields as computer science, legal affairs
and regulatory matters.
What we do
Our best-known job is to evaluate new drugs for safety
and effectiveness before they can be sold. Our evaluation,
called a review, makes sure that the drugs we approve meet
our tough standards for safety, effectiveness and quality.
We also make sure that you and your doctor will have the
information you need to use medicines wisely. Once drugs are
on the market, we monitor them for problems.
Reviewing drugs before marketing. A drug company
seeking to sell a drug in the United States must first test
it. We monitor clinical research to ensure that people who
volunteer for studies are protected and that the quality and
integrity of scientific data are maintained. The company
then sends us the evidence from these tests to prove the
drug is safe and effective for its intended use. We assemble
a team of physicians, statisticians, chemists,
pharmacologists and other scientists to review the company’s
data and proposed use for the drug. If the drug is effective
and we are convinced its health benefits outweigh its risks,
we approve it for sale. We don’t actually test the drug
when we review the company’s data. By setting clear
standards for the evidence we need to approve a drug, we
help medical researchers bring new drugs to American
consumers more rapidly. We also review drugs that you can
buy over the counter without a prescription and generic
versions of over-the-counter and prescription drugs.
Watching for drug problems. Once a drug is approved
for sale in the United States, our consumer protection
mission continues. We monitor the use of marketed drugs for
unexpected health risks. If new, unanticipated risks are
detected after approval, we take steps to inform the public
and change how a drug is used or even remove a drug from the
market. We also monitor manufacturing changes to make sure
they won’t adversely affect the safety or efficacy of the
medicine. We evaluate reports about suspected problems from
manufacturers, health care professionals and consumers.
Sometimes, manufacturers run into production problems that
might endanger the health of patients who depend on a drug.
We try to make sure that an adequate supply of drugs is
Monitoring drug information and advertising. Accurate
and complete information is vital to the safe use of drugs.
Drug companies have historically promoted their products
directly to physicians. More and more frequently now, they
are advertising directly to consumers. While it is primarily
the Federal Trade Commission that regulates advertising of
over-the-counter drugs, we regulate unapproved products that
may be marketed OTC, including their associated promotional
materials, to ensure that they meet applicable approval
requirements and are not fraudulent. Advertisements for a
drug must contain a truthful summary of information about
its effectiveness, side effects and circumstances when its
use should be avoided. We are monitoring the industry’s
voluntary program to provide consumers useful information
about prescription drugs when they pick up their
prescriptions. We are watching this program closely to see
that it meets its goals for quantity and quality of
Protecting drug quality. In addition to setting
standards for safety and effectiveness testing, we also set
standards for drug quality and manufacturing processes. We
work closely with manufacturers to see where streamlining
can cut red tape without compromising drug quality. As the
pharmaceutical industry has become increasingly global, we
are involved in international negotiations with other
nations to harmonize standards for drug quality and the data
needed to approve a new drug. This harmonization will go a
long way toward reducing the number of redundant tests
manufacturers do and help ensure drug quality for consumers
at home and abroad. We also protect drug quality with
rigorous manufacturing inspections to ensure compliance with
current Good Manufacturing Practice requirements.
Why we do it
Our present and future mission remains constant: to
ensure that drug products available to the public are safe
and effective. Our yardstick for success will always be
protecting and promoting the health of Americans.
Getting consumer input. Protecting consumers means
listening to them. We consult with the American public when
making difficult decisions about the drugs that they use. We
hold public meetings about once a week to get expert,
patient and consumer input into our decisions. We also
announce most of our policy and technical proposals in
advance. This gives members of the public, academic experts,
industry, trade associations, consumer groups and
professional societies the opportunity to comment before we
make a final decision. In addition, we take part in
FDA-sponsored public meetings with consumer and patient
groups, professional societies and pharmaceutical trade
associations. These help us obtain enhanced public input
into our planning and priority-setting practices.
What is a drug?
We regulate drugs used to treat, prevent or diagnose
illnesses. However, drugs include more than just medicines.
For example, fluoride toothpaste, antiperspirants, dandruff
shampoos and sunscreens are all considered
"drugs." You can buy some drugs in a store without
a prescription, while others require a doctor's
prescription. Some are available in less-expensive generic
Prescription medicines must be administered under a
doctor’s supervision or require a doctor’s authorization
for purchase. There are several reasons for requiring a
medicine be sold by prescription:
- The disease or condition may be serious and require a
- The medicine itself may cause side effects that a
doctor needs to monitor.
- The same symptoms may be caused by different diseases
that only a doctor can diagnose.
- The different causes may require different medicines.
- Some medicines can be dangerous when used to treat the
You can buy OTC drugs without a doctor’s prescription.
You can successfully diagnose many common ailments and treat
them yourself with readily available OTC products. These
range from acne products to cold medications. As with
prescription drugs, we closely regulate OTC drugs to ensure
that they are safe, effective and properly labeled.
A generic drug is a chemical copy of a brand-name drug.
There are generic versions of both prescription and
over-the-counter drugs. Generic drugs approved by the FDA
have the same therapeutic effects as their brand-name
We conduct and collaborate on focused laboratory research
and testing. This maintains and strengthens the scientific
base of our regulatory policy-making and decision-making. We
- Drug quality, safety and performance
- Improved technologies
- New approaches to drug development and review
- Regulatory standards and consistency
The Center for Drug Evaluation and Research promotes and
protects public health by assuring that safe and effective
drugs are available to Americans. The Food and Drug
Administration Modernization Act of 1997 affirmed the
center's public health protection role, clarified the FDA's
mission and called for the FDA to:
- Promote the public health by promptly and efficiently
reviewing clinical research and taking appropriate
action on the marketing
of human drugs in a timely manner.
- Protect the public health by ensuring that human drugs
- Participate through appropriate processes with
of other countries to reduce the burden of regulation,
harmonize regulatory requirements and achieve
appropriate reciprocal arrangements.
- Carry out its mission in consultation with experts in
science, medicine and public health and in cooperation
with consumers, users, manufacturers, importers,
packers, distributors and retailers of human drugs.
We are pleased to present our eighth performance report.
Our work last year offered many Americans new or improved
choices for protecting and maintaining their health or new
ways to use existing products more safely.
Children and adults with cancer, heart disease and other
serious conditions have benefited from our approvals in
2003. We saw improved results from the previous year on
overall approvals and decreases in the time it took us to
review and approve most applications.
A highlight was the approval of 21 new molecular entities
with active ingredients never before marketed in the United
States. This number increased from the 2002 total of 17.
Priority approvals for products of special medical
importance increased from 2002 as well. There were 14
priority NDAs and nine priority NMEs, compared to 11 and
seven in 2002, respectively..
We met all of our obligations to Congress for prompt and
thorough review of drug applications supported by user fees.
We increased choices for self-care by approving three
medicines for over-the-counter marketing. This included the
first switch of a previously prescription-only treatment for
Our reviews of generic drugs have been prompt and
predictable. We approved 263 generic equivalents for
prescription or over-the-counter drugs. These included
first-time generic approvals of treatments for depression,
seizures and high blood pressure.
Drug safety and quality
All medicines have risks. With modern, state-of-the-art
tools and techniques, we are able to detect rare and
unexpected risks rapidly and take corrective action quickly.
We processed and evaluated more than 370,000 adverse drug
events and 3,000 reports of medication errors. We proposed a
regulation that called for over-the-counter medicines
commonly used in hospitals and all prescription medicines to
have a bar code. The rule became final in 2004.
We continued to focus on managing risks of marketed
medicines, including having a public workshop to gather
consumer and scientific input on our proposals for risk
management strategies during drug development and after a
drug is marketed.
We held several public meetings to discuss our effort to
promote modernization of pharmaceutical manufacturing.
We met almost weekly with outside experts on difficult
scientific and public health issues.
Each month, our Internet information site averaged
750,000 visitors and 13.5 million hits.
We developed public education campaigns in areas such as
antibiotic resistance and buying drugs from outside the
United States. Our education program on generic drug
quality, specially funded by Congress, has been enormously
successful, with many organizations reproducing our
materials at no cost to the government.
We continued our close work with our colleagues in Japan
and the European Union on finding ways to make the drug
development process more efficient and uniform.
We entered new information-sharing agreements with
Canada, Switzerland and the European Union.
We are starting down a long road toward making major
improvements to our quality systems to improve the way we do
our work. We already have some quality systems and
subsystems in place, so we will build on those and add new
The basic concepts underlying quality systems are quite
- Say what you do.
- Do what you say.
- Prove it.
- Improve it.
FDA’s March 2004 report, Innovation or
Stagnation?-Challenge and Opportunity on the Critical Path
to New Medical Products, provides our analysis of the
There is a slowdown-instead of an expected
acceleration-in innovative medical therapies reaching
patients. The medical product development path is becoming
increasingly challenging, inefficient and costly.
As a consequence, our mission to ensure the availability
of safe and effective medical treatments for Americans that
take advantage of the latest science is becoming
In our view, the applied sciences for product development
have failed to keep pace with the tremendous advances in the
basic sciences. New science is not being used to guide the
development process in the same way that it is accelerating
the discovery process.
To focus the attention of the public, academic
researchers, funding agencies and industry, our report
- The critical path for product development from design
and discovery to commercial marketing.
- The scientific and technical dimensions of the
- The three types of research that support the critical
An idealized “critical path” encompasses the medical
product development process. The critical path begins after
basic research provides candidate products for development.
These products then face successively more rigorous
evaluation steps along the path, including:
- Drug discovery
- Preclinical development
- Clinical development
- Scale-up for mass production
- FDA filing/approval and launch preparation
A striking feature of this path is the difficulty, at any
point, of predicting ultimate success with a novel
candidate. Recent biomedical research breakthroughs have not
improved our ability to identify successful candidates.
Critical path dimensions
From the earliest phases of preclinical work to
commercialization, developers must manage successfully in
these three dimensions:
--showing that a product is
adequately safe for each stage of development.
Demonstrating medical utility
--showing a new product
will actually benefit people.
--turning a laboratory concept into
a consistent and well-characterized medical product that can
be mass produced.
The traditional tools used to assess product
safety-animal toxicology and outcomes from human
studies-have changed little over many decades and have
largely not benefited from recent gains in scientific
Better tools are needed to identify products that will
prove clinically useful and eliminate impending failures
more efficiently and earlier in the development process.
The current drug discovery process, based on in-vitro
screening techniques and animal models of often poorly
understood clinical relevance, is fundamentally unable to
identify candidates with a high probability of
effectiveness. Reaching a more systemic and dynamic
understanding of human disease will require major additional
scientific efforts as well as significant advances in
The challenges involved in successful industrialization
are complex, though highly underrated in the scientific
community. Problems in physical design, characterization,
manufacturing scale-up and quality control routinely derail
or delay development programs and keep needed treatments
Critical path research
These different types of research support medical product
is directed toward a fundamental
understanding of biology and disease processes. It
provides the foundation for product development.
is concerned with moving
basic discoveries from concept into clinical evaluation and
is often product or disease specific.
Critical path research
is directed toward improving
the medical product development process itself by
establishing new evaluation tools.
Research needed to improve development tools
While the biomedical research community has widened its
efforts to include translational research, in our report, we
call for a new focus on critical path research.
Together with academia, patient groups, industry and
other government agencies, we need to embark on an
aggressive, collaborative research effort to create a new
generation of performance standards and predictive tools
that will provide better answers about the safety and
effectiveness of investigational products, faster and with
We at FDA are uniquely suited to take a major role in
this effort because of our experience overseeing medical
product development, assessment and manufacturing/marketing;
our vast clinical and animal databases; and our close
interactions with all the major players in the critical path
The way forward
This initiative is not a fundamental departure for us,
but rather builds on our proven best practices for
developing industry guidance and expediting the availability
of promising medical technologies.
The next steps in this initiative include a series of
workshops and meetings, to start development of a National
Critical Path Opportunities list and to identify the key
The full report is available at http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html.
Pharmaceutical cGMP Initiative
Our regulatory and quality control systems for
pharmaceutical products, known as current good manufacturing
practices, have become a gold standard for the world;
however, the last comprehensive revisions to these
regulations took place nearly a quarter of a century ago.
Pharmaceutical cGMPs for the 21st Century is a
multi-year Agency effort begun in 2002 to enhance the
regulation of pharmaceutical manufacturing and product
We evaluated our internal operations under this
initiative last year:
- We are developing a quantitative, risk-based
site-selection model for use in choosing sites for
inspection. This will encourage implementation of
risk-based approaches that focus on critical areas. It
will ensure a risk-management approach is applied to
allocating FDA inspection resources.
- We revised our Preapproval Inspection Compliance
Program to give field inspectors more opportunity to use
a risk-based approach, allowing greater flexibility in
determining whether a preapproval inspection is
warranted. The number of categories of drug products
that require mandatory inspection have been reduced.
cGMP initiative goals
Public health protection is strengthened by implementing
risk-based approaches that focus both industry and our
attention on critical areas for improving product safety and
- The regulatory review program and the inspection
program operate in a coordinated and synergistic manner
- Regulation and manufacturing standards are applied
consistently using state-of-the-art pharmaceutical
- Innovation in the pharmaceutical manufacturing sector
- Our resources are used most effectively and
efficiently to address the most significant health
More information is at http://www.fda.gov/cder/gmp/index.htm.
Guidances to encourage manufacturing improvements
We issued one final and four draft guidances to encourage
rapid adoption by industry of modern manufacturing
practices. These were:
- A final guidance on the use of electronic records and
signatures. which explains the goals of this initiative
and removes barriers to scientific and technological
advances and encourages the use of risk-based
approaches. The guidance clarifies the scope and
application of Part 11 of the Code of Federal
Regulations and provides for our enforcement discretion
in certain areas while we undertake rulemaking to revise
- A draft guidance on the aseptic processes used in the
manufacture of sterile drugs, emphasizing current
science and risk-based approaches. This provides
recommendations on how to build quality into products
using science-based facilities, equipment and systems
design. Sterile drug products are generally of high
therapeutic significance, and our proactive efforts to
enhance cGMP understanding in this area are intended to
promote compliance and ensure a steady supply of these
medically necessary products to U.S. consumers.
- A draft guidance on a process for resolving disputes
arising over scientific and technical issues related to
pharmaceutical current good manufacturing practices.
- A draft guidance on preparation and use of a
comparability protocol for assessing chemistry,
manufacturing and control changes to protein drug
products and biological products.
- A draft guidance for process analytical technology, a
framework for allowing regulatory processes to adopt
more readily state-of-the-art technological advances in
drug development, production and quality assurance (page
- A collaboration with two universities to identify the
factors that predict manufacturing performance to
further refine our pharmaceutical manufacturing
- A collaboration with the National Science Foundation’s
Center for Pharmaceutical Processing Research allowing
us to expand our scientific foundation in the area of
innovative pharmaceutical manufacturing technology.
- A cooperative research and development agreement with
a major pharmaceutical manufacturer to research chemical
imaging applications in pharmaceutical manufacturing and
- A memorandum of understanding between us and FDA’s
field force to set up the Pharmaceutical Inspectorate
who will devote most of their time to conducting human
drug manufacturing quality inspections.
The first therapy for those exposed to a terrorism agent
is often a drug. We have been taking an aggressive and
proactive approach to our role in helping prepare the nation
for terrorism attacks. These steps include:
- Assuring the availability of medicines to treat
victims of terrorism attacks.
- Leveraging resources with other federal agencies to
answer scientific questions concerning therapies to
treat conditions against terrorism agents.
- Protecting the nation’s drug supply from attack or
- Preparing ourselves to continue operations during a
We continue to facilitate development of new drugs and
new uses for already approved drugs that could be used as
medical countermeasures. We work with other agencies to
implement a shelf-life extension program for stockpiled
drugs for military use. We gather information on drugs that
might be used in response to an attack, including data on
manufacturers, bulk suppliers, inventories and lead times
for production. We participate in preparedness and response
activities to test and establish appropriate communications
procedures for emergency situations. We are collaborating
with the Centers for Disease Control and Prevention on plans
for obtaining post-event outcome data on the use of medical
Counterterrorism notable 2003 achievements
- Approved pyridostigmine bromide tablets as a
pretreatment to increase survival after exposure to
Soman “nerve gas” poisoning. The product is approved
for combat use by U.S. armed forces. This is the first
drug approved under the animal efficacy rule.
- Approved lower doses of the atropine autoinjector (AtroPen)
for use in children and adolescents exposed to
certain nerve agents and insecticides. The atropine
autoinjector was approved for adult use in 1973.
- Approved insoluble Prussian blue (Radiogardase)
capsules to treat people
exposed to radiation contamination from harmful levels
of cesium-137 or thallium poisoning. The application for
this drug was sent in response to the publication of our
findings that Prussian blue would be safe and effective
for this indication when produced under conditions
specified in approved marketing applications. More
information is at http://www.fda.gov/cder/drug/infopage/prussian_blue/.
- Published our findings on intravenous chelators
for treating exposure to radioisotopes. We determined
that pentetate calcium trisodium (Ca-DTPA) and pentetate
zinc trisodium (Zn-DTPA) are safe and effective, when
produced under conditions specified in approved
marketing applications, for treatment of contamination
with radioactive isotopes of the elements plutonium,
americium and curium. We are encouraging manufacturers
to use these findings to submit new drug applications.
- Published information on the World Wide Web on how to
dissolve and mix doxycycline tablets with food or
drinks. Following an exposure to inhalational anthrax,
parents may receive stockpiled tablets for their
children if suspensions are not available. We published
these instructions for making palatable doses of the
antibiotic to give small children who may not be able to
- Participated in emergency response activities,
including the international Global Mercury smallpox
exercise and the U.S. government’s Scarlet Cloud
anthrax exercise. We also began testing components of
our continuity of operations plan to assure that we can
maintain vital operations and service.
- Began discussions with CDC on mechanisms to collect
and assess outcome information following the use of
medical countermeasures in a terrorist event.
- Drafted a guidance for industry that we published in
March 2004, Vaccinia Virus: Developing Drugs to
Mitigate Complications from Smallpox Vaccination.
Animal efficacy rule
Certain human drugs and biologics intended to reduce or
prevent serious or life-threatening conditions may be
approved based on animal evidence of effectiveness when
human efficacy studies are not ethical or feasible. The
regulation, also known as Subpart I for drugs (21 CFR Part
314) or Subpart H for biologics (21 CFR Part 601) applies
- The pathophysiology of the disease and the mechanisms
of action of the drug are reasonably well-understood.
- The efficacy endpoints in the animal trials are
clearly related to human benefit.
- The drug effect is demonstrated in more than one
well-characterized animal species expected to react with
a response predictive for humans; and
- Data allow selection of an effective human dose.
Counterterrorism scientific research
Some medical countermeasures are stockpiled in tablet
form that may be difficult to swallow for infants, small
children and others. Two examples are doxycycline, for
post-exposure prophylaxis for anthrax, and potassium iodide,
for use in emergencies involving radioactive iodine. We used
the “electronic tongue” instrument to extend our studies
of the stability and palatability of these drugs when
crushed and mixed with different foods or drinks. We
compared the results to those of human taste panels. We
developed an exposure-response model for pyridostigmine, an
anti-nerve gas agent, to extrapolate animal efficacy data to
a human dose regimen.
Counterterrorism biotechnology research
We have used congressionally mandated special funding to
initiate research in several areas relevant to
counterterrorism. Our scientists are studying:
- Microarray technologies, which could assist in
identifying infectious biowarfare agents
- Non-specific immune boosters, which could provide
transient protection against such agents
- Monoclonal antibodies as neutralizers of biological
- Various strategies to defend against anthrax
By establishing a core of scientists experienced in
several areas of bioterrorism, these projects anticipate
high-priority regulatory submissions likely to require rapid
Collaborative research on pneumonic plague
We are collaborating with the National Institute of
Allergy and Infectious Diseases and the U.S. Army Medical
Research Institute of Infectious Diseases to investigate the
use of the antibiotic gentamicin and other antimicrobials
for the treatment of pneumonic plague. Natural history,
pharmacokinetic and toxicology studies were performed to
support planned efficacy studies using a non-human primate
model of pneumonic plague.
Shelf-life extension for drug stockpiles
Our laboratories perform shelf-life extension testing for
drug products stockpiled by the U.S. military and the
Strategic National Stockpile. We published the Guidance
for Federal Agencies and State and Local Governments:
Potassium Iodide Tablets Shelf Life Extension as a
draft, and it became final in March 2004.
Counterterrorism Internet resources
We provides links to the most current information on:
- Drugs to prevent or treat disease caused by terrorism
agents including drugs for use against anthrax, plague,
radiation emergencies and chemical agents.
- Drug development of counterterrorism products.
- Pediatric counterterrorism measures.
- Prescribing and buying countermeasures.
You can find these links at http://www.fda.gov/cder/drugprepare/default.htm.
We advance the scientific basis of regulatory practice by
developing, evaluating or applying the best, most
appropriate and contemporary scientific methods to
regulatory testing paradigms. We provide scientific support
for reviewer training, regulatory decision making and the
development of regulatory policy.
We focus on creating a tighter scientific linkage between
non-clinical and clinical studies, enhancing methodology for
assuring product quality, building databases for improved
drug development and review and providing regulatory support
through laboratory testing.
Linking nonclinical and clinical studies
- We are identifying, evaluating and establishing
relvant protein biomarkers in blood in both animal
models and in humans. These will help detect the very
earliest damage that can be caused by certain drugs to
the heart, kidney, immune system and liver.
- To enhance safety within broad segments of patient
populations and enable safe development of new drug
classes, we are working on the identification and
elucidation of associated serum biomarkers and
mechanisms responsible for the development of vascular
inflammation in specific organ systems.
- We conduct targeted research on microarrays, a new
technology that can identify thousands of genes or
proteins rapidly and at the same time. We are evaluating
how this technology could improve the interface between
drug development and regulatory practice.
- We established scientific research capabilities in the
analyses of medicinal plant and herbal products.
- We continue to explore noninvasive imaging technology
to extend our long-standing interest in the application
of accurate dose-concentration-response principles by
viewing drugs and their actions directly at the level of
the drug target, rather than indirectly via plasma
- We are developing a standardized approach for using
exposure-response information to help evaluate the risks
and benefits of drug therapies and recommending dose
adjustments in special populations.
- We are developing a pediatric population
pharmacokinetics study design template to facilitate
implementation of sparse sample strategies in pediatric
Our new Office of Biotechnology Products was officially
transferred in 2003 from the Center for Biologics Evaluation
and Research. The office consists of about 80 scientists who
are responsible for evaluating therapeutic biotechnology
product submissions as well as carrying out scientific
research related to biologics regulatory issues.
- We review many submissions aimed at inhibiting
unwanted immune responses, such as autoimmune diseases
or rejection of transplanted organs, or aimed at
enhancing desired immune responses, such as those
against infections or cancer. To facilitate review of
such immunology-related submissions, we study the
mechanisms by which immune cells are activated,
suppressed or channeled from one kind of active response
- We study the mechanisms by which various regulated
products induce their intended effects, as well as
unintended adverse effects. Our investigations also
examine various normal and pathogenic pathways that are
targeted by regulated agents.
Our research enhances the ability of our
scientist/regulators to evaluate risks and benefits of
biotech products, to advise industry on difficult regulatory
problems, such as potency assays, and to develop hands-on
expertise in the modern technologies used by sponsors of
Informatics and computational safety analysis
- Our cooperative research and development agreements
with several commercial software developers have
resulted in the development and marketing of new
computer software to predict the cancer-causing
potential of chemicals based on their molecular
structure. The software makes use of our extensive
rodent carcinogenicity database without compromising
- We have successfully developed computer models to
estimate the safe starting dose for clinical trials of
drugs based on their molecular structure. The current
method for estimating the starting dose is highly
inexact and requires the use of multiple safety factors
because it is based exclusively on an extrapolation from
animal toxicity studies. We have begun studies to
validate the new method.
- We are exploring the utility and value of quantitative
drug-disease state models and clinical trial simulation
in drug development and regulatory review.
- We issued the final guidance on Exposure-Response
Relationships: Study Design, Data Analysis, and
- We cosponsored an open workshop pharmacogenomics in
drug development and regulatory Decision-making.
- We published a draft guidance for industry, Pharmacogenomic
Data Submissions, to provide a better understanding
on the current use of pharmacogenomics in drug
development and gain experience in handling and
evaluating genotype and gene expression data.
- We are working on a draft guidance for industry on the
regulatory pathway for pharmacogenomic drug-device
- We assure that analytical methods being developed by
pharmaceutical companies are suitable for quality
assurance and regulatory purposes. We assessed
analytical methods for six new drugs and one generic
- We collaborate with other organizations to ensure the
availability of high quality standards and calibration
- We collaborated with state pharmacy boards to evaluate
- We evaluated the quality of a select group of the
most-often-ordered pharmaceutical products from foreign
Last year our efforts included:
- Assessment of the safety (cyanide release) and the
efficacy (cesium binding) of Prussian blue in support of
its approval as a medical countermeasure.
- Development of methods to evaluate quality attributes
of drug products and raw materials by chemical imaging.
These properties include polymorphic form, hydration
state, stability and purity.
- Rapid identification of counterfeit products using
near-infrared spectroscopy and chemical imaging to
discriminate drug products and raw materials.
- Development of a methodology for the determining glove
permeability to lindane shampoo and lotion, treatments
for lice whose active ingredient is highly toxic.
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Date created: May 24, 2004