CDER Report to the Nation: 2005
Improving Public Health Through Human Drugs
Slides of charts for presentations
CDER 2007 Update: Improving Public Health Through Human Drugs
I am pleased to provide our 2005 Report to the
Nation from the Center for Drug Evaluation and Research.
In this report, we outline our initiatives and
document our performance across our program areas during 2005. I am
very proud to report that we have made substantial advances in
identifying, managing and communicating safety-related issues. We
have also made major advances in our efforts to improve the science
of drug manufacturing.
As an organization, our Center is becoming more
transparent, flexible, results-oriented and high-performing. These
improvements are helping us maintain our place as the world leader
in the review of the safety and efficacy of pharmaceutical products
and in responding to the challenges of emerging public health
threats. Through our participation in the FDA’s Critical Path
Initiative, we are playing a key role in helping to enhance the
efficiency of drug development. Although, we play an important role
in many areas, I would like to focus on just a few key efforts to
give you an idea of what we are doing to ensure the success of our
Addressing public concerns about drug safety
All medicines have benefits and risks. We have
continued to focus on the importance of minimizing these risks and
improving the way medicines are used. For example, during 2005, we
issued 16 public health advisories about important drug safety
issues. To sustain a multi-disciplinary, cross-Center approach to
drug safety, we elevated the Office of Surveillance and Epidemiology
(formerly the Office of Drug Safety) to report directly to the
Center Director, and we appointed an Associate Center Director for
Safety, Policy and Communication to focus on broad drug-safety
policy and communication, including overseeing MedWatch and the Drug
Safety Oversight Board staff. We anticipate that this reorganization
will help us successfully promote the efficient assessment of and
response to emerging safety issues.
In addition, the creation last year of the Drug
Safety Oversight Board continues to foster a culture of openness and
enhanced oversight around safety issues within the Center. In 2005,
the board, under chair Douglas Throckmorton, M.D., the Center’s
Deputy Director, met five times and discussed critical safety issues
including: long-acting beta agonists associated with more severe
asthma episodes; Clostridium
sordellii infections in patients taking mifepristone;
antidepressants and suicidality; and the concerns with misuse of
fentanyl transdermal patches. The board continues to work to help us
improve how we identify and manage emerging drug safety issues and
how we provide emerging information to health-care professionals and
patients about the risks and benefits of medicines.
Improving our analytic and predictive tools to enhance drug
One of the organizational changes announced in
2005 is a response to FDA’s efforts to improve the science of
medical product development, the Critical Path Initiative. To
support this priority activity and to speed the movement of
innovative therapies to patients, we created an Office of
Translational Sciences, which includes the Office of Clinical
Pharmacology and the Office of Biostatistics. The Office of
Translation Sciences will support cross-cutting science programs
such as the Regulatory Science and Review Enhancement Committee, the
Research Involving Human Subjects Committee and the Critical Path
Initiative. This office also has the important task of coordinating
our collaborations with outside groups to help identify and resolve
issues that are standing in the way of efficient drug development.
We anticipate that, by putting these functions together into one
office, we will be better able to promote these many scientific
Improving our scientific tools to ensure product quality
We are continuing our work on the
transformation of product manufacturing and how it is regulated, by
extending the work done in the Agency-wide Pharmaceutical cGMPs for
the 21st Century initiative. Activities have included:
- Incorporating the fundamentals of quality systems into CDER
- Restructuring the chemistry, manufacturing and controls review staff
in the Office of New Drug Quality Assessment to provide for better
- Rolling out concepts and philosophy of the changes to industry.
- Training chemistry, manufacturing and controls reviewers
- Introducing a pilot program for new drugs through which industry can
submit applications using a quality-by-design framework to help
expand the Agency’s knowledge in this area.
All of these activities have helped strengthen
the overall scientific focus for chemistry, manufacturing and
controls review as well as reduce some of the regulatory burden for
both the Agency and the industry.
Improving efficiency and consistency of cancer product reviews
Our efforts to improve the timely development
of new drugs for the treatment of cancer have continued. To enable
this, we made significant changes to our organizational structure to
provide a stronger and more consistent approach to the review
process for drugs and therapeutic biologics used to diagnose, treat
and prevent cancer. We created a new oncology office, called the
Office of Oncology Drug Products. This new office is a consolidation
of three pre-existing areas within the Center: Drug Oncology
Products, Biologic Oncology Products and Medical Imaging and
Hematology Products. Creation of this new office will improve
consistency of review and policy for oncology products and bring
together a critical mass of oncologists who can help during the
development of new cancer therapies. This office will also provide
technical consultation to other FDA components.
Speeding the development of medical countermeasures
We recognize the need to facilitate the
development of countermeasures to protect Americans from biological,
chemical, nuclear and radiological agents of terrorism. Many parts
of the Center contribute to this effort, focused through the Office
of Counter-Terrorism and Emergency Coordination, an office we formed
in 2006. One important goal we have identified is to foster the
development of medical countermeasures for vulnerable populations.
For example, in 2005, following an expedited review, we approved
ThyroShield, a ready-to-use, liquid medicine to block the uptake of
radioactive iodine in vulnerable populations. Unlike already
approved tablets, which are not ideally suited for young children,
this black raspberry flavored solution is dosed using an eyedropper
to enable easy treatment of young children and newborns.
We are extremely proud of the work outlined in
this report and look forward to another year of important strides in
approving therapies to improve the health of Americans.
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 U.S. 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 2,200
employees. Approximately half of us are physicians or other
kinds of scientists.
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 safe and
effective 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
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 it from the
market. We monitor changes in manufacturing to make sure
they won’t adversely affect safety or efficacy. We evaluate
reports about suspected problems from manufacturers,
health-care professionals and consumers. We try to make sure
an adequate supply of needed drugs is always available to
patients who depend on them.
Monitoring drug information and advertising. Accurate
and complete information is vital to the safe use of drugs.
We regulate information that accompanies or is displayed
with an over-the-counter drug. In the past, drug companies
promoted their products almost entirely to physicians. More
frequently now, they are advertising directly to consumers.
We oversee advertising of prescription drugs, whether to
physicians or consumers. We pay particular attention to
broadcast ads that can be seen by a great many consumers.
The Federal Trade Commission regulates advertising of
over-the-counter drugs. Advertisements for a drug must
contain a truthful summary of information about its
effectiveness, side effects and circumstances when its use
should be avoided.
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. To
ensure a safe and effective drug supply, we enforce federal
requirements for drug approval, manufacturing and labeling.
When necessary, we take legal action to stop distribution of
products in violation of these requirements. 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.
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
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 versions.
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 wrong
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
counterparts, often at a much lower cost.
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
are safe and effective.
- Participate through appropriate processes with
representatives 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.
Highlights and Initiatives
We are pleased to present our 10th performance report. Our
work in 2005 offered many Americans new or improved choices for
protecting and maintaining their health or new ways to use existing
products more safely. We worked hard at our mission of ensuring that
Americans have safe and effective drugs and also developed these
initiatives to bring the latest science and technology to bear on
- Reforming our drug
- Identifying ways
to improve the science of drug development.
- Protecting the
homeland with improved medical countermeasures to be used in
the event of a terrorist attack or disaster.
targeted scientific research to improve our regulatory
- We accomplished our work on these
initiatives while maintaining our performance on our reviews
of safety and efficacy and our oversight and surveillance of
the safety of products sold to Americans.
We approved 80 new medicines, including 20 truly new
medicines that had not been marketed in any form before in
this country. We approved 141 new or expanded uses for
already approved medicines. We approved 344 generic versions
of existing drugs.
User-fee performance. We met almost all of our goals for review
performance in fiscal year 2005.
safety surveillance. We processed and evaluated more
than 460,000 reports of adverse drug events, including more
than 25,000 submitted directly from individual health-care
providers and patients.
promotion and advertising. We issued 60 letters on
violations in drug promotion and more than 800 letters to
help ensure manufacturers comply with regulations concerning
database of electronic labels. We required
manufacturers to begin submitting drug labeling information
electronically so that it can be made publicly available
health advisories. We issued alerts on non-steroidal
anti-inflammatory pain medicines and 15 other safety
We acted to halt distribution of drugs that were unapproved,
poorly manufactured or improperly labeled.
Our highest priority is assuring that
safe and effective medicines are available to the American
public. Safe medicines, where the benefits outweigh the
risks, were the focus of a number of high-profile
initiatives in 2005. We worked to ensure that our systems
for assessing and evaluating safety continue to be robust
and that we communicate new information for health-care
providers and patients in a timely and clear manner. Our
- Establishing the
Drug Safety Oversight Board.
- Sharing drug
safety information sooner and more broadly.
- Laying the
foundations of an electronic information infrastructure that
will give patients, health-care professionals and consumers
quick and easy access to the most up-to-date and accurate
information on medicines.
- Obtaining public
input on our drug risk communications strategies.
Comprehensive oversight of drug safety
Our professional staff spends about one-half
their time addressing safety issues, including:
- Watching for problems once we approve
- Overseeing clinical trials.
- Evaluating new therapies and new or
expanded uses for existing therapies to balance risks against
- Overseeing manufacturing, distribution
and promotional activities.
- Preventing medication errors by
evaluating proposed proprietary names, labeling and packaging.
- Developing proactive risk management
strategies both before and after approval.
Drug Safety Oversight Board
The 15-member board provides drug
safety oversight and recommendations to the Center Director
on drug safety issues. The board held five meetings in 2005.
In its initial meetings, members explored the methods we use
in risk assessment of marketed drugs, including:
- Review and
analysis of spontaneous reports of adverse events.
- Drug use data.
- Epidemiologic and
- Clinical trials.
- Active surveillance systems.
In later meetings, members discussed pre- and
post-decisional risk management examples to further clarify
and define their oversight and advisory responsibilities
including their role in helping establish policies and
managing the communication of important drug safety issues
to stakeholders. Members include representatives from each
of our offices with responsibility for drug safety, a
representative from each of the two other FDA centers
dealing with human medical products, a representative the
Veterans Administration and a representative the National
Institutes of Health.
More information about the board is at
Public summaries of board meetings are
Drug safety communication channels
We began sharing “emerging” drug safety
information broadly through public health advisories and
through specific drug safety information sheets that are
tailored to the needs of health-care professionals and
patients. In some cases, we are sharing safety information
even before we have reached conclusions that would prompt a
regulatory action. Our communications in 2005 included:
Health Advisories. We issued 16 advisories to alert
health-care providers and consumers to safety concerns about
drugs. Public Health
professional information sheets. We published sheets
on 44 drugs with detailed information about emerging
important drug safety concerns, including a description of
the concern along with recommendations and considerations
about the concern for the prescriber.
information sheets. We published 41 information
sheets containing new information about emerging drug safety
concerns for approved drugs and provided in a
More about drug safety communication is
Prescription drug information infrastructure
Accurate, up-to-date information about
a prescription drug is critical for its safe and effective
use. Too frequently, information about a prescription drug
reads more like a legal disclaimer than useful or actionable
health information. We worked hard in 2005 to bring to
fruition several interconnected regulatory actions,
submission of drug labeling. We issued final guidance
to assist manufacturers in submitting prescription drug
label information to us in a new electronic format.
the DailyMed public database of drug information.
This multi-agency effort to improve patient safety is
enabling us—through the National Library of Medicine—to
provide an up-to-date electronic repository of medication
labeling in a standard format. This information will be
useable in computer systems that support patient safety,
such as electronic prescribing and decision-support systems.
to bring out our final requirement for revised prescription
drug labeling. Our final regulation, issued in
January 2006, amends the content and format of prescription
drug information, commonly called the package insert. The
new label will provide the most important information about
new and recently approved prescription drugs and new uses in a
format that is better understood, more easily accessible and
more memorable for physicians.
Public hearing on communication of drug
Making us a reliable
“trusted source” of health-care provider and consumer
information about medicines emerged as the key theme at a
two-day public hearing in 2005 on our risk communications.
We were urged to engage health-care professional
organizations, simplify our risk communications, improve
provider and consumer access to our Internet site, develop
consistent communication approaches and address those with
limited health literacy and English skills.
Critical Path Initiative
Our role in the
Agency’s Critical Path Initiative is to stimulate and
facilitate a national effort to modernize the scientific
processes through which a potential human drug or
therapeutic biologic is transformed from a discovery or
“proof of concept” into a medical product.
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, an FDA
report in 2004 described an urgent need to modernize the
medical product development process—the Critical Path—to
make product development more predictable and efficient.
Because of our unique vantage point, we can work with
companies, patient groups, academic researchers and other
stakeholders to coordinate, develop and help disseminate
solutions to scientific hurdles that are impairing the
efficiency of medical product development.
Critical Path Opportunities List
During 2005, we helped
the Agency describe and provide examples of how new
scientific discoveries—in fields such as genomics,
proteomics, imaging and bioinformatics—could be applied to
improve the accuracy of the tests we use to predict the
safety and efficacy of investigational medical products. The
list was released in early 2006.
The list provides a
concrete focus for public and private efforts and
investments in new tools that could revolutionize product
development. The goal is to encourage others to undertake
such work in their areas of interest. It was developed based
on feedback from stakeholders and the special insights of
FDA’s product reviewers.
The list’s 76
scientific projects mark a starting point in identifying the
essential development priorities. These are highly-targeted
research projects divided into six key areas:
- Better evaluation
tools—biomarkers and disease models.
- Streamlining clinical trials.
- Harnessing bioinformatics.
- Moving manufacturing into the 21st
- Products to address urgent
public health needs.
- At-risk populations.
The comprehensive Web
site on the Critical Path is at
The Critical Path recognizes
“pharmacogenomics” and encourages its use in drug
Pharmacogenomics allows health-care
providers to identify differences in people’s drug risk response
profiles and predict the best possible treatment options for
In 2005, we helped lay the regulatory
groundwork for pharmacogenomics in the Critical Path by
- A final guidance on voluntary
submissions of pharmacogenomic data
- A draft concept paper on how
to co-develop a drug or biological therapy along with a
device test in a scientifically robust and efficient way.
We received 15
voluntary genomic data submissions from industry in 2005.
More information is
In 2005, we held the third in a series
of scientific workshops on how pharmacogenomics could
enable efficient and successful drug development in such
- The efficiency and
informativeness in clinical trials.
- Clinical trials for cancer
International harmonization of
Strategies to bridge
pharmacogenomics information from drug development research
to clinical practice.
- Clinical qualification of
genomic biomarkers for decision making.
Creation of diagnostic tests for clinical practice.
21st Century Drug
Our overhaul of the regulatory and
quality control systems for pharmaceutical products
encourages manufacturers to modernize their methods,
equipment and facilities. Our goal is to help eliminate both
production inefficiencies and undue risks for consumers. Our
initiative implements improved policies that are making
better use of our limited resources through more targeted
and effective inspections.
Collectively, our policies are known as
“current good manufacturing practices” or cGMPs, and our last
comprehensive revisions to them took place nearly a quarter of a
century ago. Pharmaceutical cGMPs for the 21st Century
is the umbrella name for this strategic initiative,
and more information is available at
New drug quality assessment
Our chemists reorganized during
2005 to transform drug quality assessment from a checklist review to
a scientifically sound, risk-based process. The mission of our new
Office of New Drug Quality Assessment is to:
- Assess the critical quality attributes
and manufacturing processes of new drugs.
- Establish quality standards to assure
safety and efficacy
Facilitate new drug development.
Our chemists are now focusing
on critical pharmaceutical quality attributes and their relevance to
safety and efficacy. These include chemistry, pharmaceutical
formulation, stability, manufacturing processes, bioavailability and
product performance. Our long-term goal is to:
- Emphasize quality by design in the
evaluation of critical aspects of pharmaceutical quality.
- Have a strong focus on manufacturing
- Integrate review and inspection
- Use modern statistical methodologies.
Our vision for “desired state” in manufacturing
- Product quality and performance
assured by effective and efficient manufacturing processes.
- Product attributes based on
mechanistic understanding of how formulation and process impact
- Continuous improvement and continuous
real-time assurance of quality enabled.
- Regulatory policies recognize level of
product and process knowledge.
Workshop explores drug quality system
We held a three-day scientific workshop for
industry to explore how we can achieve the new drug quality system.
We worked with industry scientists to:
- Identify scientific training gaps that
must be filled for the successful implementation of the new system.
- Obtain industry input on building a
scientific, risk-based regulatory system that maintains high quality
and facilitates continuous improvement.
- Help determine how to best use information from the
pharmaceutical development phase in the industrialization phase.
- Identify the roles and responsibilities for industry
and us in the new system.
- Propose ways to reduce the number of post-marketing
Chemistry, manufacturing, controls pilot program
We launched a formal pilot program in July 2005
under which pharmaceutical companies can voluntarily submit new drug
applications that apply quality-by-design principles and demonstrate
their product knowledge and process understanding. This scientific
information—more relevant than found in a traditional
submission—-will enable us to:
- Perform a risk-based assessment of
product quality and process performance.
- Consider an applicant’s proposal for
regulatory flexibility in setting product specifications and
We have been taking an aggressive and
proactive approach to our role in helping to prepare the
nation for terrorist events, emerging health threats and
emergency response to natural and man-made crises,
- Assuring the availability of medicines
during a crisis.
- Addressing issues on procurement,
packaging, labeling, use and shelf-life extension of products in the
Strategic National Stockpile.
- Utilizing regulatory mechanisms to
provide emergency access to new therapies and to approved therapies
used in novel ways.
- Assuring alternative manufacturing
sites for critical medicines.
- Protecting the nation’s drug supply
from attack or deliberate contamination.
- Leveraging with other federal agencies
to answer scientific questions about treatments for emerging health
threats and terrorist events.
- Preparing ourselves to continue
operations during a crisis.
Post-event surveillance planning.
Along with the FDA’s other medical
centers and the Centers for Disease Control and Prevention, we
developed a plan to identify processes for collecting adverse event
and outcome data on medical products distributed in response to an
- Project BioShield prioritization.
We participated in many interagency
counterterrorism working groups that have contributed to gap
analyses in medical countermeasures and authored many of the
requirements documents that will be used to prioritize products for
development and eventual procurement under BioShield.
Counterterrorism guidances published in 2005
- Draft Guidance for Industry:
Internal Radioactive Contamination-Development of Decorporation
- We participated in developing FDA’s
Draft Guidance: Emergency Use Authorization of Medical Products.
Medical countermeasure approvals
- Potassium iodide oral solution (ThyroShield).
This oral solution of a thyroid blocking agent for use in radiation
emergencies is appropriate for children or adults who cannot swallow
tablets. We advised the Department of Health and Human Services in a
BioShield procurement of the product, which was approved as a
- Generic ciprofloxacin.
We approved four additional new generic
ciprofloxacin drug products, all with approved labeling for the
management of inhalational anthrax (post-exposure).
- Revised labeling for ciprofloxacin
(Cipro). We approved revisions for the
sections of the package insert concerning Indications and Usage,
Adverse Reactions and Inhalational Anthrax—Additional Information.
These changes for the tablets, intravenous solution and oral
suspension were based on information obtained by the Centers for
Disease Control and Prevention during the 2001 anthrax attacks.
Because of these data, we released the manufacturer from its
accelerated approval commitment to report data from confirmatory
Facilitating medical countermeasure development
The Centers for Disease Control and Prevention continued to enroll
patients in the second year of an FDA-funded clinical trial to
assess the efficacy of the antibiotic gentamicin for endemic plague
in Madagascar, where antimicrobial options for plague are extremely
limited. We contributed to protocol design and the formation of a
data safety monitoring board to oversee the safe conduct of the
study. We are continuing our collaboration with FDA’s Center for
Devices and Radiological Health to evaluate the performance of a
novel, rapid, bedside plague diagnostic test kit under study
- Pneumonic plague.
We also continued our collaboration with the
National Institute of Allergy and Infectious Diseases and the U.S.
Army Medical Research Institute of Infectious Diseases to evaluate
the safety and efficacy of five antibiotics—gentamicin,
ciprofloxacin, levofloxacin, doxycycline and ceftriaxone—in a
non-human primate model of pneumonic plague.
- Inhalational Anthrax.
We continued our collaboration with both institutes to establish a
non-human primate natural history model for inhalational anthrax.
- Radiological and nuclear threats.
We continued to collaborate with the
National Institute of Allergy and Infectious Diseases to identify
promising new products for use against radiological and nuclear
threats. We discussed scientific and regulatory issues with
manufacturers of such products and informed them about possible
funding sources, both for early development and for procurement by
the federal government.
Pandemic flu preparedness
We are preparing for an
influenza pandemic by:
- Participating in the FDA Pandemic
Influenza Preparedness Task Force, as well as in the Antiviral
Subgroup and the Emergency Preparedness, Response and Communications
- Helping to develop FDA’s Pandemic
Influenza Preparedness Strategic Plan and our center’s portion of
FDA’s Pandemic Influenza Continuity of Operations Plan.
- Providing input on the HHS Pandemic
Influenza Plan from the Department of Health and Human Services.
We assisted in the response to
hurricanes Katrina, Rita and Wilma by coordinating the Internet
posting of information about:
- The safety of medications potentially
damaged by flooding or high temperature.
- Safety of using combination sunscreen
and insect repellent in children.
- Reporting prescription drug sample
- Assisting investigators conducting
clinical trials in hurricane-affected areas.
- Facilitating donation of drugs.
- Coordinating volunteer responses for
About 150 Public Health Service
Commissioned Corps officers—one-half the total assigned to our
center—were deployed to provide medical and pharmacy services in
areas affected by the hurricane.
We provided rapid responses to
requests for information on medical countermeasures during a
five-day interdepartmental exercise, known as TOPOFF 3 (“Top
Officials”). The exercise simulated simultaneous terrorist attacks
using multiple threat agents—both pneumonic plague in New Jersey as
well as the release of mustard gas and a high-yield explosive in
Emergency use authorization
We worked with the Centers for
Disease Control and Prevention to identify potential medical
countermeasures in the Strategic National Stockpile as candidates
for Emergency Use Authorization for an unapproved use under the
Project BioShield Act of 2004.
We also began to outline the
internal processes and procedures we need to handle emergency use
Flu prevention for children
In December, we approved
oseltamivir (Tamiflu) for prevention (prophylaxis) of
influenza in children 1 to 12 years of age. This gives health-care
providers an option for preventing influenza in children following
close contact with an infected individual.
Our approval followed
presentation of an adverse event safety update on the drug to the
Pediatric Advisory Committee. The meeting provided a public forum to
discuss the safety of the drug’s use in children as part of a
routine drug safety update required by the Best Pharmaceuticals for
We provide the most current
information on medical countermeasures and vaccines, plus advice on
purchasing and taking medication, at
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
- Biomarkers for organ damage.
We are identifying, evaluating and establishing
relevant 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
- Biomarkers for inflammation.
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.
Evaluation of microarrays.
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
- Medicinal plants, herbs.
We established scientific research capabilities
in the analyses of medicinal plant and herbal products.
- Imaging drug targets.
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 concentrations.
- Better use of exposure-response
data. 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.
- Pediatric pharmacokinetics.
We are developing a pediatric population
pharmacokinetics study design template to facilitate implementation
of sparse sample strategies in pediatric drug development.
Our Office of Biotechnology
Products consists of about 80 scientists and other staff 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 to another.
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 biotech products.
Informatics and computational safety analysis
- Cancer toxicity predictive
software. 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
- Safe starting dose models.
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.
Scientific research in pregnancy and lactation
for studies to evaluate fetal safety from
drug exposure or whether the dose of a drug should be adjusted
during pregnancy or lactation.
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 toxins.
- Various strategies to defend against
- Development of Anthrax Toxin assays
for assessment of potential therapies.
By establishing a core of scientists
experienced in several areas of bioterrorism, these projects
anticipate high-priority regulatory submissions likely to require
rapid science-based evaluation.
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Date created: August 18, 2006