CDER
Report to the Nation: 2005
Table
of Contents
Print version
Slides of charts for presentations
Drug Review
(continued)
Index
Pediatric Drug Development
The Best Pharmaceuticals for Children Act of 2002 (BPCA)
renewed our authority to grant six months of additional
marketing exclusivity to manufacturers who conduct and
submit pediatric studies in response to our written
requests. In calendar year 2005, we approved 25 pediatric
labeling changes as a result of studies conducted under the
exclusivity provision.
Pediatric exclusivity. As of April
30, 2006, we had received 467 proposed pediatric study
requests from manufacturers, issued 320 written requests,
made 130 exclusivity determinations, granted exclusivity to
118 drugs and added new pediatric information to 109 labels.
Improved safety, dosing information.
About one-fourth of the new
pediatric labels have safety or dosing information. We are
discovering important differences between adults and
children in the clearance and metabolism of drugs.
Underdosing leads to ineffective treatment, and overdosing
poses a greater risk of adverse reactions. Pediatric safety
signals identified in these studies include effects on
growth, school behavior, suppression of the adrenal gland
and suicidal ideation. The failure to produce drugs in
dosage forms that can be taken by young children—such as
liquids or chewable tablets—can deny them access to
important medications. As a result of pediatric testing we
now have 12 drugs with new pediatric formulations and six
drugs with recipes in their labels to provide directions for
the pharmacist to compound an age-appropriate formulation.
Off-patent drugs.
The law also established a publicly funded contracting
process to study drugs that lack patent protection or market
exclusivity, referred to as “off-patent.” In consultation
with FDA and other pediatric experts, the National
Institutes of Health have published five lists of off-patent
drugs for which additional pediatric studies are needed. To
date, we have issued 17 written requests—five in 2005—for
these off-patent drugs. We also have forwarded eight written
requests – two in 2005-for on-patent drugs, for which
sponsors declined pediatric studies.
Public disclosure.
We publish a summary of the medical and clinical
pharmacology reviews of the pediatric studies conducted
under the law. As of April 30, 2006, we have posted 60
summaries, regardless of the regulatory action, at
http://www.fda.gov/cder/pediatric/Summaryreview.htm.
Adverse events reported.
The act mandates review of all adult and pediatric adverse
event reports for a one-year period after pediatric
exclusivity is granted. The reviews of the reports are then
presented to the Pediatric Advisory Committee. As of April
2006, reports for 54 drugs have been presented. Significant
pediatric safety signals have been found, including neonatal
withdrawal with antidepressant use during pregnancy and
serious adverse events, including deaths, due to fentanyl
transdermal use in children.
Pediatric Research Equity Act of 2003
In September 2005, we published a draft guidance on how
to comply with the law. The law gave us the authority to
require pediatric studies of certain new drugs and
biological products when such studies are needed to ensure
the safe and effective use of the products in children.
However, the law does not require the same public disclosure
of pediatric studies required under the Best Pharmaceuticals
for Children Act.
2005 new
approvals with pediatric indications
n
New molecular entities.
Two orphan treatments for children who are very short for
their age and an iron chelating agent indicated for patients
2 and older.
n
Biologics.
An enzyme replacement therapy for a rare inherited condition
that can affect children.
n
New drugs.
An oral solution of an antiretroviral
medicine
and four over-the-counter drugs.
Safety issues for children’s uses
We issued
Public Health Advisories
about pediatric safety issues including:
n
A boxed warning about using the eczema
therapies pimecrolimus and tacrolimus only as directed
and not at all in children younger than 2 years of age.
n
Suicidal thinking in children and
adolescents treated with atomoxetine for attention deficit
hyperactivity disorder.
We added a black box warning about suicidality in
children and adolescents to the labeling for antidepressants. Full
information and a list of the drugs is at
http://www.fda.gov/cder/drug/antidepressants/default.htm.
2005 pediatric drug statistics
n
10 written requests issued n 25 pediatric exclusivity labeling changes granted n 15 exclusivity determinations made
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Notable 2005 pediatric new or
expanded uses
The Best Pharmaceuticals for Children Act
requires us to give priority status to pediatric supplements
for drug studies submitted in response to a written request.
An efficacy supplement may change labeling to reflect new
information about pediatric use, even if there are no new or
expanded uses. The review of these pediatric supplements
resulted in labeling that describes new and expanded uses of
these medications in children:
Ertapenem sodium (Invanz),
an injectable antibiotic, had its labeling expanded to include the
treatment of susceptible moderate to severe infections in children 3
months of age and older. Clinical pharmacokinetic studies proved
that ertapenem is not recommended in the treatment of meningitis in
the pediatric population due to lack of sufficient CSF penetration.
Ethinyl estradiol and norgestimate (Ortho Tri-Cyclen),
an oral hormone combination, had its labeling revised to indicate
that there was no significant difference between treatment and
placebo in bone mineral density in 123 adolescent females with
anorexia nervosa in a one-year clinical trial.
Insulin aspart (NovoLog),
a rapid-acting injectable human insulin analog,
labeling was expanded to include treatment of patients 6 to 18 years
old with type 1 diabetes.
Levetiracetam (Keppra),
available as tablets and oral solution, labeling was
expanded to include use as adjunctive therapy in the treatment of
partial onset seizures in pediatric patients 4 years and older with
epilepsy.
Meloxicam
(Mobic), a nonsteroidal anti-inflammatory drug available as
tablets and oral suspension, labeling was expanded to include
treatment of certain types of juvenile rheumatoid arthritis in
patients 2 years of age and older.
Mixed salts of a single entity amphetamine (Adderall
XR), a once or twice daily
extended-release central nervous system stimulant, labeling expanded
to include treatment of attention deficit hyperactivity disorder in
patients 13 to 17 years of age. Previously approved for use in
children 6 to 12 years old.
Ondansetron (Zofran),
an antiemetic available as tablets and an injectable, labeling
expanded to include dosing in children down to 6 months of age for
the prevention of chemotherapy-induced nausea and vomiting, as well
as dosing in children down to 1 month of age for the prevention of
postoperative-induced nausea and vomiting. Labeling previously
provided dosing down to 4 years of age for the prevention of
chemotherapy-induced nausea and vomiting and dosing down to 2 years
of age for the prevention of postoperative-induced nausea and
vomiting.
Oxcarbazepine (Trileptal),
an anticonvulsant available as tablets and oral suspension, labeling
expanded to include treatment as adjunctive therapy in children aged
2 years and above with epilepsy. Previously approved for children 4
years and older. In clinical studies, it was observed that children
2 to <4 years of age may require up to twice the dose per body
weight compared to adults.
Sibutramine (Meridia),
a weight loss aid, labeling modified to reflect that data from a
clinical study in obese adolescents are inadequate to recommend the
use of sibutramine for the treatment of obesity in pediatric
patients. In addition, important safety information was added.
Notable non-BPCA pediatric new or expanded use
Nitazoxanide (Alinia)
can be used to treat diarrhea caused by
Cryptosporidium parvum in non-HIV infected patients 12 years
of age and older.
2005 priority pediatric labeling changes
Our priority review of
these pediatric supplements was consistent with the BPCA
unless noted:
n
Alendronate sodium
n
Amphetamines, Mixed salts
n
Ertapenem
n
Gemcitabine hydrochloride
n
Glimepiride
n
Insulin aspart recombinant
n
Levetiracetam [2]
n
Linezolid [3]
n
Meloxicam [3]
n
Nefazodone
n
Nitazoxanide [2](unrelated to BPCA)
n
Ethinyl estradiol and norgestimate
n
Ondansetron
n
Oxcarbazepine [2]
n
Ritonavir [2]
n
Rosiglitazone
n
Sibutramine
n
Sirolimus [2]
Internet resources
Our Web site for up-to-date
pediatric labeling changes is at
http://www.fda.gov/cder/pediatric/index.htm.
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Pregnancy and Lactation
Labeling
To improve our knowledge of the use of
drugs during pregnancy and lactation, we sponsor research
and provide scientific guidance to industry and our
reviewers.
Women who are pregnant often need to use prescription medicines.
In many cases, a disease or condition left untreated may be more
harmful to a woman and her fetus or nursing baby than a drug
treatment. In other cases, a different drug treatment than she is
already on may be safer.
We have reviewed the current system of labeling drugs for use by
pregnant and lactating women and are developing an improved, more
comprehensive and clinically meaningful approach. We are consulting
with government agencies, medical experts, consumer groups and the
pharmaceutical industry to develop this new labeling format. We work
with our reviewers and pharmaceutical companies to update product
labels with available human data regarding exposure to drugs during
pregnancy and lactation.
Scientific guidance
n
Risks of drug exposure in human
pregnancies. In 2005, we issued our final
guidance for our reviewers on how to evaluate human data on the
effects of in utero drug exposure on the developing
fetus.
n
Lactation studies in women.
In 2005, we published a draft guidance for industry that provides
the basic framework for designing, conducting and analyzing clinical
lactation studies.
n
Determining the appropriate dose of
a drug for pregnant women. In 2004, we
published a draft guidance for industry that provides the basic
framework for designing, conducting and analyzing pharmacokinetic
and pharmacodynamic studies in pregnant women.
n
Pregnancy exposure registries.
In 2002, we published a final guidance for industry that provides
advice on how to establish registries that prospectively monitor the
outcomes of pregnancies in women exposed to a specific drug. These
registries can provide clinically relevant human data for treating
or counseling patients who are pregnant or anticipating pregnancy.
Scientific research in pregnancy and lactation
We funded several studies to evaluate
either fetal safety from drug exposure or whether the dose
of a drug should be adjusted during pregnancy or lactation:
n
Counter-terrorism.
These studies look at specific anti-infective drug
products that would be used for treatment following exposure to
specific bioterrorism agents. They focus on use in special patient
populations, such as women who are pregnant or lactating and the
elderly. They evaluate either the need for dose adjustments in these
special patient populations or fetal safety following in
utero drug exposure.
n
Liver enzymes.
These studies look at the effects of pregnancy on specific
drug-metabolizing enzymes in the liver.
Research on drugs for high blood pressure,
depression
FDA’s Office of Women’s Health
funded studies to look at specific drugs used to treat high blood
pressure and depression and determine if the doses of these drugs
should be adjusted during pregnancy.
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Over the Counter Drug
Review
Over-the-counter drug statistics
n
5 approvals for first-time OTC sale
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Over-the-Counter Drug Review
We approved five new drug applications
for first-time over-the-counter sale. There were no
prescription-to-OTC switches or new uses approved in 2005.
Our OTC approvals were:
n
Ibuprofen
and diphenhydramine hydrochloride (Advil PM
Liquigels and Caplets) for relief of occasional
sleeplessness associated with pain in adults.
n
Loratadine (Loratadine Oral
Suspension) for the temporary relief of
these symptoms due to hay fever or other upper respiratory
allergies: runny nose, sneezing, itchy, watery eyes, itching of the
throat or nose in adults and children 2 years of age and older.
n
Chlorhexidine gluconate (2%
Chlorhexidine Gluconate Cloth) for use as
a patient preoperative skin preparation in adults and children 2
months of age and older.
n
Loperamide (Loperamide HCl soft
gelatin capsules) to control symptoms of
diarrhea, including traveler’s diarrhea in adults and children 6
years of age and older.
n
Chlorhexidine gluconate
and isopropyl alcohol (Chlorascrub Swab,
Chlorascrub Swabstick and Chlorascrub Maxi Swabstick) for
use as a patient pre-injection preparation and as a patient
preoperative skin preparation (Chlorascrub Swabstick and
Chlorascrub Maxi Swabstick) in adults and children 2 months of
age and older.
Office of Nonprescription Products created
We created an Office of
Nonprescription Products in our reorganization of the Office of New
Drugs. Within the office, the Division of Nonprescription Clinical
Evaluation focuses mainly on the review of investigational new drugs
and new drug applications. The Division of Nonprescription
Regulation Development focuses mainly on the development of OTC drug
monographs.
Improved labels for OTC medicines
American consumers are benefiting from
easy-to-understand labels on drugs they buy without a prescription.
A mandatory changeover to the new labels, titled “Drug Facts,” began
in 2002 and is now complete for all products, with a few exceptions,
as of May 2005.
How we regulate OTC drugs
We publish monographs that establish acceptable
ingredients, doses, formulations and consumer labeling for OTC
drugs. Products that conform to a final monograph may be marketed
without prior FDA clearance. Drugs also can be approved for OTC sale
through the new drug review process. More information about the OTC
drug review process is at
http://www.fda.gov/cder/about/smallbiz/OTC.htm.
Education campaign on safe use of OTCs
We developed a national
education campaign to provide advice on the safe use of
over-the-counter pain and fever reducers (http://www.fda.gov/cder/drug/analgesics/).
Because many OTC medicines for different uses have the same active
ingredients, an unintentional overdose is possible. We are focusing
on OTC drug products that contain acetaminophen and non-steroidal
anti-inflammatory agents, which include products such as aspirin,
ibuprofen, naproxen sodium and ketoprofen.
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Generic Drug Review
Generic drug statistics
n
344 generic drug approvals n Median approval time:
16.4 months n
108 tentative approvals n
777 receipts
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We approved 344 generic drug products in 2005, including a
substantial number of products that represent the first time
a generic drug was available for the brand-name product.
The median approval time was 16.4 months. The median
statistic for total approval time had hovered at about 18 to
19 months for six years. We have made several changes to
improve the efficiency of our generic drug review process in
order to try to keep up with the dramatic increase in
applications. These efforts will continue.
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Notable 2005 generic drug
approvals
Examples of first-time generic drug
approvals are:
n
Azithromycin.
An antibiotic used for the treatment of mild to
moderate infections of various types.
n
Fentanyl transdermal system.
Used for managing chronic pain.
n
Fexofenadine.
Used to relieve seasonal allergic rhinitis symptoms.
n
Levofloxacin.
A broad spectrum antibiotic used for various conditions such as
pneumonia, bronchitis and sinusitis.
n
Ramipril.
Used to treat high blood pressure, heart failure
after a heart attack and risk reduction for certain cardiac events.
n
Zidovudine.
Used in combination with other antiretroviral agents for the
treatment of HIV infection.
Our approval of generic versions of these drugs can save American
consumers and the federal government hundreds of millions of dollars
each year.
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Tentative vs. full approval
The only difference between a full approval and a tentative
approval is that the final approval of these applications is delayed
due to an existing patent or exclusivity on the innovator drug
product. These and other legal issues continue to be a challenge to
the generic drug review program.
The review of an application that is tentatively approved
requires the same amount of work as a review that results in a full
approval.
While tentative approvals represent a full workload for us, they
are only displayed in our approvals chart once they are converted to
full approvals. For example, some of the approvals in 2005 represent
conversions of tentative approvals granted in 2004 or previous
years.
Tentative approvals key to affordable, worldwide AIDS
relief
Tentative approval is a key
regulatory mechanism to support the availability of drugs
for the President’s Emergency
Plan for AIDS Relief.
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How we approve generic drugs
Generics are not required to
repeat the extensive clinical trials used in the development
of the original, brand-name drug. For many products such as tablets
and capsules, the generics must show bioequivalence
to the brand-name reference listed drug. This means that the
generic version must deliver the same amount of active
ingredient into a patient’s bloodstream and in the same time
as the brand-name reference listed drug. The rate and extent of absorption
is called bioavailability. The bioavailability of the
generic drug is then compared to that of the brand-name.
This comparison is bioequivalence. Brand-name drugs are subject to
the same bioequivalency tests as generics when their
manufacturers reformulate them.
Scientific basis for generic drug review
We continue to articulate the
scientific underpinnings of our review process and to work
to define mechanisms to evaluate equivalence of certain
unique products.
Online education
We are offering a free online
educational tutorial on the generic drug approval process
that offers one hour of continuing education credit for
certain health professionals. The course, available at
http://www.connectlive.com/events/genericdrugs/,
educates health professionals on how our approval assures
that generic drugs are safe, effective and high quality
products.
Improving manufacturing practices
The strategic initiative to develop a
21st century drug
quality system
also applies to generic drugs.
Consumer communication
Our efforts to build consumer
confidence in generic drug products are continuing through
our Generic Drug Quality Awareness program. We have partnered with a number of
professional and consumer organizations to launch programs
about the quality and benefits of generic drugs. We have
helped design messages that appear on prescription bags in
chain drug stores. Radio public service announcements with
the generic drug quality message will be appearing in
several geographic areas.
Our generic drug public service
announcements are at
http://www.fda.gov/cder/consumerinfo/generic_info/default.htm.
Generic drug Web site
You can find more information about our generic drug program at
http://www.fda.gov/cder/ogd/.
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Generic drug review
efficiencies
The dramatic increase in receipts of
generic drug applications makes it imperative that we
process generic drug applications more efficiently. With the
overall goal of getting generic drug products to the
consumer as efficiently as possible, we continue to look for
ways to improve our processes and also to provide
communication and guidance to industry.
We are taking steps aimed at improving
the content and completeness of generic drug applications
and assuring that the applications contain the needed
information to be evaluated successfully in one cycle. These
steps include:
n
Enhanced communication with individual
applicants during the review process.
n
Working with the generic drug industry
association to help their members submit applications that
can be reviewed more efficiently.
n
Exploring further enhancements to the review
process.
n
Holding joint meetings and workshops with
industry to enhance knowledge of topics of interest.
n
Efforts to encourage submission of
applications in an electronic format for greater efficiency.
Electronic submissions
Through public presentations, we are
encouraging the generic drug industry to submit their
applications electronically.
Restructuring to meet increased demands
We have constituted a third chemistry review division for
generic drugs. We also are augmenting our clinical,
microbiology and bioequivalence review staffs to meet the
needs for review of a growing number of generic drug
applications.
Reducing hurdles to generic drug availability
We are working on regulations to decrease time-consuming
legal delays in the approval and marketing of generic
products. These rules, implementing provisions of the
2003 Medicare Prescription Drug, Improvement and
Modernization Act, will:
n
Limit an innovator firm to one 30-month delay for courts to
resolve patents challenged by an generic manufacturer.
n
Prevent a generic manufacturer with 180-day exclusivity from
delaying marketing in order to deny other generic firms
entry into the market.
More generic competition
results in lower drug prices
The entry of a second generic
competitor brings about the largest price reduction. We concluded
this from our analysis of IMS retail sales data for
single-ingredient brand-name and generic drug products sold from
1999 through 2004. Our study is at
http://www.fda.gov/cder/ogd/generic_competition.htm.
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Assessing Data
Quality, Research Risks
Inspections for data quality, research risks in 2005
We conducted a total of 652
inspections in 2005:
n
284 U.S. clinical investigators
n 70 foreign clinical investigators
n
122 institutional review boards
n 31 sponsors, monitors or contract research
organizations
n 56 good laboratory practices
n 89 in-vivo bioequivalence
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When obtaining data about the safety
and effectiveness of drugs, sponsors rely on high quality
laboratory studies and human volunteers to take part in
clinical studies. Protecting volunteers from research
risks is a critical responsibility for us and all involved
in clinical trials.
We perform on-site inspections to protect the rights and
welfare of volunteers and verify the quality and integrity
of data submitted for our review. We inspect domestic and
foreign clinical trial study sites; institutional review
boards; sponsors, monitors and organizations conducting
research; laboratories that obtain data; and
sites
performing bioequivalence studies in humans
and preclinical studies in animals.
Our programs to protect volunteers are
challenged by increases in the number of clinical trials,
the types and complexity of products undergoing testing, and
the increased number of trials performed in countries with
less experience and limited or no standards for conducting
clinical research.
Sponsors and clinical investigators
protect volunteers by ensuring that:
n
Clinical trials are appropriately designed and
conducted according to good clinical practices.
n
Research is reviewed and approved by an
institutional review board.
n
Informed consent is obtained from
participants.
n
Ongoing clinical trials are actively
monitored.
n
Special attention is given to protecting
vulnerable populations, such as children, the mentally
impaired and prisoners.
We require sponsors to disclose
financial interests of clinical investigators who conduct
studies for them. This helps identify potential sources of
bias in the design, conduct, reporting and analysis of
clinical studies.
Top 5 deficiencies found during inspections of clinical
investigators in 2005
n
Failure to follow the protocol
n Failure to keep adequate and accurate records
n Failure to account for the disposition of study
drugs
n Failure to report adverse events
n Problems with the informed consent form
International inspections of clinical research
We conducted 70 inspections of clinical research in 25
countries in 2005. We participate in international efforts
to strengthen protections for human volunteers worldwide and
encourage clinical investigators to conduct studies
according to the highest ethical principles. This includes
our work with the International Conference on Harmonization and the
Declaration of Helsinki.
Internet resources
More information on data integrity
and patient safety is at
http://www.fda.gov/cder/offices/dsi/index.htm.
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Electronic Submissions
We cooperated with outside organizations
working to publish standards for submitting study data.
These groups include the Clinical Data Interchange Standards
Consortium and Health Level 7, also known as CDISC and HL-7
respectively. Some of these projects are:
n
Clinical trial data.
We adopted the consortium’s Study Data Tabulation
Model version 1.0 for submission of information from clinical
trials.
n
Preclinical data.
The consortium is working to extend the model to handle animal
toxicity and microbiology data.
n
Database development.
We completed a database model for storing and accessing both
clinical and animal toxicity data submitted using the Study Data
Tabulation Model. We are collaborating with the National Cancer
Institute and software vendors to implement the database and develop
“smart” tools for accessing the data.
n
Electrocardiogram data.
We adopted the Health Level 7 standard for annotated
electrocardiogram waveform data. We are working with a vendor to
develop software for analyzing the data and a warehouse for storing
it.
n
Structured product labeling.
We are accepting Health Level 7 Structured
Product Labeling for content of labeling submissions. We are
developing a repository for storing the data and software to improve
the processing and reviewing of labeling changes. This is part of
our effort to improve patient safety through access to the most
recent information about medicines.
We continue to receive electronic submissions using the
specifications of the electronic Common Technical Document.
Electronic submission of labeling required
In 2005, we issued final guidance to assist manufacturers in
submitting prescription drug label information to us in a new
electronic format. These electronic product labels are the key element and
primary source of medication information for “DailyMed”—a new
interagency online health information clearinghouse that will
provide the most up-to-date medication information free to
consumers, health-care providers and health-care information
providers.
Using embedded computer tags, the prescribing and
product information can be electronically managed, allowing a user
to search for specific information. These tags can instruct
computers to read specific sections of a drug label including
product names, indications, dosage and administration, warnings,
description of drug product, active and inactive ingredients, and
how the drug is supplied.
With this information, physicians will be able to quickly search and
access specific information they need before prescribing a
treatment, resulting in fewer prescribing errors and better informed
decision making. In addition, the electronic labels will improve our
drug labeling review process, so that we can provide immediate
access to the most recent information about medications to
prescribers and patients.
Internet resources
More information on our electronic submissions
program is at
http://www.fda.gov/cder/regulatory/ersr/.
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User Fee Program
Americans deserve timely access to
potentially lifesaving new drugs as soon as possible once
they are proven safe and effective. The Prescription Drug
User Fee Act of 1992 received its second five-year extension
in 2002, known as PDUFA III. This reauthorization is helping
us ensure that we have the expert staff and resources to
review applications promptly and get safe, effective new
drugs into the hands of the people who need them. The
current user fee law maintains our high review performance
goals, includes increased consultations with drug sponsors
and provides for earlier feedback on their submissions.
User fee performance
Under legislation authorizing us to collect
user fees for drug reviews, we agreed to specific performance goals
for the prompt review of submissions.
n
We exceeded all our performance goals
for the fiscal year 2004 receipt cohort.
n
We are on track for exceeding most
user-fee performance goals for the fiscal year 2005 cohort.
Continuous marketing application pilot programs
Under PDUFA III, we are assessing the value of both early review
of parts of marketing applications and of more extensive feedback to
sponsors during their development programs. Two pilots for
“continuous marketing applications” apply to drugs and biologics in
our fast track program:
n
Pilot 1
allows applicants to submit predefined portions of their marketing
applications called “reviewable units” before submitting the
completed application. Each reviewable unit has a six-month goal for
issuing a discipline review letter. In fiscal year 2005, we met our
performance goal for reviewable unit submissions.
n
Pilot 2
allows us to enter into agreements with sponsors for frequent
scientific feedback and interactions during the clinical trial phase
of product development. As of Aug. 1, 2005, there were nine
development projects entered in the Pilot 2 program.
The pilots have limitations and specific criteria
for entry. More information is available at
http://www.fda.gov/cder/pdufa/CMA.htm.
Internet resources for user fees
Our user fee Web site at
http://www.fda.gov/cder/pdufa/default.htm has
links to PDUFA:
n
Legislation
n Federal Register
documents
n Guidances
n Letters
n Performance reports
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Drug Review Team
We use project teams to perform
reviews. Team members apply their individual special
technical expertise to review applications:
n
Biologists, biochemists and
immunologists evaluate the manufacturing processes for
biological products to ensure the continued purity, potency
and safety of these products. They also provide insights to
the review team regarding the mechanism of action and
potential and observed adverse events associated with
specific products.
n
Chemists focus on how a drug is
manufactured. They make sure the manufacturing controls,
quality control testing and packaging are adequate to
preserve the drug product’s identity, strength, potency,
purity and stability.
n
Clinical pharmacologists and
biopharmaceutists evaluate factors that influence the
relationship between the body’s response and the drug dose
and evaluate the rate and extent to which a drug’s active
ingredient is made available to the body and the way it is
distributed, metabolized and eliminated. They also assess
the clinical significance of changes in the body’s response
to drugs through the use of exposure-response relationships
and check for interactions between drugs.
n
n
Microbiologists evaluate the effects of
anti-infective drugs on germs. These medicines—antibiotics,
antivirals and antifungals—differ from others because they
are intended to affect the germs instead of patients.
Another group of microbiologists evaluates the manufacturing
processes and tests for sterile products, such as those used
intravenously.
n
Pharmacologists and toxicologists
evaluate the effects of the drug on laboratory animals
in short-term and long-term studies, including the potential
based on animal studies for drugs to induce birth defects or
cancer in humans.
n
Physicians evaluate the results of the
clinical trials, including the drug’s adverse and
therapeutic effects, and determine if the product’s benefits
outweigh its known risks at the doses proposed.
n
Project managers orchestrate and
coordinate the drug review team’s interactions, efforts and
reviews. They also serve as the regulatory expert for the
review team and as the primary contact for the drug
industry.
n
Statisticians evaluate the designs and
results for each important clinical study.
Scientific training for reviewers
Our systematic, internal training
program is based on core competencies, learning pathways and
individual development plans. In 2005:
n
We presented 30 scientific seminars and scientific rounds.
n
We offered a strong and innovative curriculum of 45
scientific courses.
n
We brought in 49 visiting professors to talk directly to
individual review divisions about critical, new drug-related
research and techniques.
n
We offered additional courses in job skills, research tools,
leadership and management.
Advanced scientific education
A committee of our scientists
oversees a program of scientific training, seminars, case
study rounds and guest lectures. This multidisciplinary program
helps keep our scientists up-to-date on the latest
developments in their fields and current industry practices.
Academics to CDER
Each spring, we collaborate with
five local universities to present an up-to-date course on a
compelling scientific topic. Recent topics were:
n
2005: Critical path science
n 2005: Exposure-response concepts
n 2003: Drug safety
n 2002: Pharmacogenetics
n 2001: QT prolongation
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Date created: August 18, 2006 |