CDER
Report to the Nation: 2005
Table of
Contents
Print version
Slides of charts for presentations
1 Drug Review
Index
Highlights
Many Americans benefited from
last year’s timely reviews of new prescription medicines,
over-the-counter medicines and the generic equivalents for both.
When we review a medicine, we use the best science available to
determine if a medicine’s benefits outweigh its risks for its
intended use. An internal study showed that about half of our
professional staff time is spent on safety assessment. We oversee
the development of new medicines in the United States, and our
paramount concern is the safety of patient volunteers in clinical
trials.
Highlights for 2005 include:
n
80 new medicines.
We approved 78 drugs and two biologics (22 priority and 58 standard
reviews).
n
20 truly new medicines.
We approved 18 drugs and two new biologics that had
never been marketed before in any form in this country (15 priority
and 5 standard reviews).
n
141 new treatment options.
We approved new or expanded uses for 126 already approved drugs
and 15 already approved biologics (36 priority and 105 standard
reviews).
n
5 over-the-counter drugs.
Our approvals included five new medicines to be sold over the
counter without a prescription, and four of them can be used by
children. We approved three new uses for existing OTCs, all of which
can be used by children.
n
10 “orphan” medicines.
Our approvals included nine drugs and one biologic for patient
populations of 200,000 or fewer.
n
344 generic drugs.
We gave final approval to 344 generic versions of existing drugs and
tentative approval to another 108. We received 777 marketing
applications for generic drugs.
n
User fee goals.
We exceeded all our performance goals for the fiscal year 2004
receipt cohort, the latest year for which we have full statistics.
We are on track for exceeding most user-fee performance goals for
the fiscal year 2005 cohort.
n
652 clinical trial inspections.
We conducted foreign and domestic
inspections that help protect volunteers in clinical trials from
research risks and validate the quality and integrity of data
submitted to us.
New drug review consolidated at White Oak campus
Most of our review
operations, except for generics, were successfully consolidated in a
new facility in White Oak, Md. We took advantage of the move to
reorganize the Office of New Drugs in a way that created logical
groupings in the same divisions, created divisions with better
balanced workloads and resource allocation and completed the
integration of biologics reviewers and indications within our review
divisions.
Within OND,
we renamed two offices—the Office of Oncology Drug Products and the
Office of Antimicrobial Products. We created a new
Office of
Nonprescription Products with two divisions.
Review of
psychiatric and neurological products was separated into two
divisions.
More
information is at
http://www.fda.gov/cder/cderorg/ond_reorg.htm.
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New Drug and Biologic Review
Definitions
n
New drug applications.
NDAs are the formal submissions
of data that sponsors send us when they are seeking approval
to market a “new drug” in the United States. Some NDAs are
NMEs; however, “new drugs” can also include an active
substance previously sold in a different form.
n
New molecular entities.
NMEs contain an active substance that has never
before been approved for marketing in any form in the United States.
Because of high interest in truly new medicines, we report approvals
of NMEs and “new BLAs.” The charts for all NDAs and all BLAs include
NMEs and new BLAs.
n
Biologic license application.
BLAs are the formal submissions of data
that sponsors send us when they are seeking approval to market a
biologic in the United States. A “new BLA” is a biologic that has
never been approved for marketing in the United States.
n
Review and approval times.
Review time represents the time that we spend
examining the application. Approval time represents our review time
plus industry’s response time to our requests for additional
information.
n
Priority approvals.
These products represent significant improvements compared with
marketed products. We have a goal of reviewing 90 percent of these
applications within six months.
n
Standard approvals.
These products have therapeutic qualities similar to those of
already marketed products. We have a goal of reviewing 90 percent of
these applications within 10 months.
n
Actions and filings.
An application is “filed” when we determine it is
complete and accept it for review. We make a filing decision within
60 days of receiving an application. Approval is one of the actions
that we can take once an application is filed. Other actions include
seeking more information from the sponsor. There is no direct
connection between applications filed in one year and actions in the
same year.
n
Orphan drugs.
We administer a program that provides incentives to develop drugs
for use in patient populations of 200,000 or fewer. Sponsors of
orphan drugs receive inducements that include seven-year marketing
exclusivity, tax credit for the product-associated clinical
research, research design assistance from FDA and grants of up to
$200,000 a year.
n
Accelerated approval.
This program helps make products for serious or
life-threatening diseases available earlier in the development
process. We base our approval on a promising effect of the drug that
can be observed significantly sooner than a long-term clinical
benefit. Sponsors perform additional studies to demonstrate
long-term clinical benefit.
n
Fast track development.
This program facilitates the development and
expedites our review of new drugs and biologics that demonstrate the
potential to address unmet medical needs for serious or
life-threatening conditions. Fast track emphasizes our close, early
communication with sponsors.
n
Median times.
Our charts show review and approval times as
“medians.” The value for the median time is the number that falls in
the middle of the group after the numbers are ranked in order. It
provides a truer picture of our performance than average time, which
can be unduly influenced by a few very long or short times. Our
guide to understanding median approval time statistics is available
at
http://www.fda.gov/cder/present/MedianAPtime/index.htm.
Therapeutic BLAs included starting with 2004 data
Beginning with 2004, our charts
incorporate data on the review of therapeutic biologics
transferred to us in late 2003. These include:
n
Monoclonal antibodies.
n Cytokines.
n Growth factors.
n Enzymes.
n Other therapeutic immunotherapies.
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NDA and BLA Review Statistics
Approval totals
n
80 drugs and biologics
o
78 drugs
o
2 biologics
n
20 truly new medicines
o
18 drug NMEs
o
2 new biologics
n
14 orphan approvals
o
9 NDAs (includes 6 NMEs)
o
1 new biologic
o
4 approvals for 3 new or expanded
uses
Priority new drugs and biologics
n
22 approvals
o 20 drugs
o 2 biologics
n
Median review time: 6.0 months
n Median approval time: 6.0
months
n
29 filings
n 36 actions
n
9 orphan approvals
o 8 drugs (6 NMEs)
o 1 new biologic
Click image for larger chart,
click here for accessible
text.
Click image for larger chart,
click here for accessible
text.
Priority new molecular entities and
new biologics
n
15 approvals
o 13 NMEs
o 2 new BLAs
n
Median review time: 6.0 months
n Median approval time: 6.0
months
n
17 filings
Click image for larger chart,
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text.
Click image for larger chart,
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text.
Standard drugs and biologics
n
58 approvals
o 58 drugs
n
Median review time: 11.8 months
n Median approval time:
13.1 months
n
82 filings
n
107 actions
n
1 orphan approval
Click image for larger chart,
click here for accessible
text.
Click image for larger chart,
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text.
Standard new molecular entities and
new biologics
n
5 approvals
o
5
NMEs
n
Median review time: 15.8 months
n Median approval time:
23.0 months
n
19 filings
Click image for larger chart,
click here for accessible
text.
Click image for larger chart,
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text.
Listing of NMEs, new BLAs, other
priority NDAs
NMEs
(P=priority, S=standard,
O=orphan)
n
Conivaptan hydrochloride (S)
n
Deferasirox (P, O)
n
Entecavir (P)
n
Exenatide (S)
n
Hyaluronidase (P)
n
Hyaluronidase human (P)
n
Insulin detemir (S)
n
Lenalidomide (P, O)
n
Mecasermin [rDNA origin] (P,
O)
n
Mecasermin rinfabate [rDNA
origin] (P, O)
n
Micafungin sodium (P)
n
Nelarabine (P, O)
n
Nepafenac (P)
n
Pramlintide acetate (S)
n
Ramelteon (S)
n
Sorafenib tosylate (P, O)
n
Tigecycline (P)
n
Tipranavir (P)
New BLAs
n
Abatacept (P)
n
Galsulfase (P, O)
Other NDA priority
approvals
(T=tentative)
n
Emtricitabine (new
formulation)
n
Entecavir (new formulation)
n
Fluocinolone acetonide (new
formulation, O)
n
Lamivudine; zidovudine;
nevirapine (new combination, T)
n
Lopinavir; ritonavir (new
formulation)
n
Sildenafil citrate (new
formulation)
n
Sodium benzoate; sodium
phenylacetate (new formulation, O)
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Drugs@FDA
Drugs@FDA—the most frequently used
application on the FDA Web site—has official information
about FDA approved brand-name and generic drugs such as:
n
Approved and tentatively approved drug products.
n The regulatory history of an approved drug.
n Labels for approved drug products.
n All drugs with a specific active ingredient.
n Generic drug products for a brand-name drug
product.
n Therapeutically equivalent drug products for a
brand-name or generic drug product.
n Consumer information for drugs approved after
1998.
To use Drugs@FDA, go to
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
Internet resources for drug review statistics
n
Additional statistics. More review statistics are
available at
http://www.fda.gov/cder/rdmt/default.htm.
n
Data updated. You should be aware that these data may
differ from those in previous issues of this report. We have
revised data from previous years.
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Notable 2005 New Approvals
Last year’s approvals benefited children,
people with HIV infection, cancer, diabetes and other disorders.
Children
Emtricitabine (Emtriva)
is an oral solution of an antiretroviral medicine that can be used
in combination with other antiretroviral agents for the treatment of
HIV infection in children 3 months old and older. The drug, first
approved as a capsule for adults in 2003, is an HIV nucleoside
reverse transcriptase inhibitor that helps to block an enzyme needed
for HIV to multiply. Related to Best Pharmaceuticals for Children
Act. (priority)
Mecasermin [rDNA origin] (Increlex)
and Mecasermin rinfabate [rDNA
origin] (Iplex) are for the long-term treatment of children who
are very short for their age because their bodies do not make enough
insulin-like growth factor-1. Both drugs contain human insulin-like
growth factor-1 from genetically engineered bacteria, but mecasermin
rinfabate also contains insulin-like growth factor binding
protein-3 from genetically engineered bacteria. (2 NMEs,
priorities, orphans)
People with HIV infection
Lopinavir/ritonavir (Kaletra)
is a new formulation in a tablet form that may be prescribed for
once-daily use in combination with other anti-HIV medicines for some
patients who have not taken anti-HIV medications in the past.
(priority)
Tipranavir (Aptivus)
is a protease inhibitor taken with 200 mg of ritonavir and two other
anti-HIV medicines to treat adults with HIV infection. The drug
blocks HIV protease, an enzyme needed for HIV to make more virus.
Tipranavir helps reduce the amount of HIV in the blood and keep the
immune system healthy so it can help fight infection.
(NME, priority)
Lamivudine/zidovudine/nevirapine
is the first three-drug HIV regimen in one package approved for
purchase under the President’s Emergency Plan for AIDS Relief. We gave it “tentative approval”
in less than two weeks because patent or exclusivity provisions
prevent its sale in the United States. It can also serve as a
reference product for generic versions. (priority)
People with cancer
Nelarabine (Arranon)
is a chemotherapy drug for the treatment of patients with T-cell
acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose
disease has not responded to or has relapsed following treatment
with at least two chemotherapy regimens. (NME, priority,
orphan)
Sorafenib tosylate (Nexavar)
is a chemotherapy agent indicated for the treatment of patients with
advanced cancer of the kidney cells. (NME, priority,
orphan)
People with infections
Entecavir (Baraclude),
in tablets and oral solution, treats chronic infection with
hepatitis B virus in adults who also have active liver damage.
Entecavir, a nucleoside analogue, competes with a natural substance
needed for viral replication. The tablet form was counted as an NME.
We also provided priority approval to a separate application for the
oral solution. (1 NME, both priorities)
Micafungin sodium (Mycamine)
is used to prevent fungal infections caused by Candida
in patients who are undergoing a stem-cell transplantation.
Micafungin inhibits synthesis of a component of the fungal cell
wall. (NME, priority)
Tigecycline (Tygacil)
treats adults who have complicated skin or intra-abdominal
infections caused by certain strains of bacteria. It belongs to the
glycylcycline class of antibiotics. (NME, priority)
People with eye disease
Fluocinolone acetonide
intravitreal implant (Retisert) treats
chronic non-infectious inflammation of the tissue in the rear of the
eye. The drug product is surgically implanted into the affected eye
and slowly releases an inflammation-controlling steroid over
approximately the next 30 months. (orphan)
Nepafenac (Nevanac)
treats the pain and inflammation associated with cataract surgery.
Nepafenac is a nonsteroidal anti-inflammatory and analgesic prodrug.
After topical ocular dosing, nepafenac penetrates the cornea and is
converted by eye tissue to amfenac, a nonsteroidal anti-inflammatory
drug. (NME, priority)
People with arthritis
Abatacept (Orencia)
treats adults with moderate to severe rheumatoid arthritis who have
not been helped by other medicines. Abatacept may be used alone or
with other arthritis medicines except those known as TNF
antagonists. Abatacept modulates parts of the immune system
implicated in causing rheumatoid arthritis. (biologic,
priority)
People with other rare disorders
Deferasirox (Exjade)
is an iron chelating agent for the treatment of chronic iron
overload due to blood transfusions in patients 2 years of age and
older. (NME, priority, orphan)
Galsulfase (Naglazyme)
is an enzyme replacement therapy for
patients with mucopolysaccharidosis VI. Also known as MPS VI or
Maroteaux-Lamy syndrome, the inherited condition results when the
body fails to make sufficient enzymes to break down certain complex
carbohydrates that then accumulate and cause widespread cellular,
tissue and organ dysfunction. The biotechnology product provides an
injectable enzyme that helps the body break down the appropriate
proteins. (biologic, priority, orphan)
Lenalidomide (Revlimid)
treats people with transfusion-dependent anemia due to low or
intermediate-1 risk myelodysplastic syndromes that are associated
with a specific genetic abnormality. The syndromes result when the
bone marrow does not make enough normal blood cells. Patients may
need blood and platelet transfusions and antibiotic therapy for
infections. In clinical trials, most patients treated with the drug
became independent of transfusions by three months, and the
transfusion-free period lasted for an average of 44 weeks. Because
the drug is structurally similar to thalidomide, which is known to
cause severe birth defects, it is sold under a risk management plan
designed to prevent fetal exposure. (NME, priority,
orphan)
Hospitalized people with dangerously low sodium
Conivaptan hydrochloride
(Vaprisol) is an
injectable medicine and the first indicated to treat hospitalized
patients with a potentially life-threatening condition that occurs
when the body’s blood sodium level falls significantly below normal.
Known as euvolemic hyponatremia, the condition is the most common
electrolyte disorder in clinical medicine and one of the most
difficult to treat. It often results from elevated levels of
antidiuretic hormone, a
hormone that regulates water and salt balance in the body. The drug
blocks the activity of this hormone, resulting in increased
urine output without loss of valuable electrolytes such as sodium
and potassium. (NME)
People with pulmonary hypertension
Sildenafil citrate (Revatio)
treats pulmonary arterial hypertension to
improve exercise ability. This serious condition, which can lead to
fatal heart failure, is caused by continuous high blood pressure in
the artery carrying blood from the heart to the lung.
(priority)
People with diabetes
Pramlintide acetate
(Symlin)
is an injectable medicine for adult patients with either type
1 or type 2 diabetes. It slows down the movement of food through the
stomach. This affects how fast sugar enters the blood after eating.
It is always used with insulin to help lower blood sugar during the
three hours after meals. The synthetic drug is similar to a
naturally occurring human hormone that contributes to blood sugar
control after eating a meal. (NME)
Exenatide
(Byetta)
is used to help improve blood sugar control in patients with
type 2 diabetes who have not achieved adequate control on metformin,
a sulfonylurea or a combination of metformin and a sulfonylurea. The
drug, chemically different from other diabetes treatments, enhances
insulin secretion, suppresses inappropriately elevated secretion of
a hormone that raises blood sugar and slows emptying of the stomach.
(NME)
Insulin detemir
[recombinant DNA origin]
(Levemir) can be
injected once or twice a day under the skin by patients with type 1
or type 2 diabetes who require a long-acting insulin for the control
of high levels of blood sugar. Because the medicine, made by
recombinant DNA technology, differs slightly from human insulin, it
is released more slowly to target tissues. (NME)
People with insomnia
Ramelteon (Rozerem)
treats insomnia in adults where the problem is
trouble falling asleep. The drug is active at the body’s melatonin
receptors, which are thought to be involved in the maintenance of
the circadian rhythm underlying the normal sleep-wake cycle.
(NME)
Treatment and diagnostic aids
Hyaluronidase (Hydase) and
Hyaluronidase human (Hylenex recombinant) help increase the
absorption and dispersion of other injected drugs and improve
resorption of X-ray contrast agents. The first drug is a purified
enzyme derived from cow tissue, and the second is a purified
preparation of the human enzyme hyaluronidase produced by
genetically engineered hamster cells. (2 NMEs, priorities)
Other priority approval
Sodium benzoate/sodium
phenylacetate (Ammonul) was approved to
be manufactured by a different company. The drug, first approved in
1987 and discontinued by its original manufacturer, helps treat
acutely elevated levels of ammonia and associated brain swelling in
patients with deficiencies in enzymes of the urea cycle.
(priority, orphan)
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New or Expanded Use Review
Applications for a new or expanded use,
often representing important new treatment options, are
formally called “efficacy supplements” to the original new
drug application.
We have a goal of reviewing standard
supplements in 10 months and priority supplements in six
months.
New or expanded use review
statistics
Approval totals
n
141 drugs and biologics
o 126 drugs
o
15
biologics
Priority new or expanded uses
(efficacy supplements)
n
36 approvals
o 34 drugs
o
2 biologics
n
Median review time: 6.0 months
n Median approval time: 6.0 months
n
52 actions
n
4 orphan approvals for 3 new or expanded uses
n
Drugs with new or expanded
uses in children approved
under priority review required by the Best Pharmaceuticals
for Children Act.
Click image for larger chart,
click here for accessible
text.
Click image for larger chart,
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text.
Standard new or expanded uses
(efficacy supplements)
n
105 approvals
o 92 drugs
o 13 biologics
n
Median review time: 10.0 months
n Median approval time: 10.0 months
n
171 actions
Click image for larger chart,
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text.
Click image for larger chart,
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text.
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Notable 2005 new or expanded use
approvals
People infected with both hepatitis and
HIV
Peginterferon alfa-2a (Pegasys),
when used alone or in combination with Ribavirin,
had its indication expanded to include treatment of adult chronic
hepatitis C patients co-infected with HIV, who have clinically
stable HIV disease. (priority, biologic)
Ribavirin (Copegus),
when used in combination with peginterferon alfa-2a, can now be used
to treat chronic hepatitis C in adult patients co-infected with HIV.
(priority)
People with cancer
Bortezomib (Velcade)
can be used to treat multiple myeloma patients who have received as
least one prior therapy instead of the two prior therapies indicated
in the 2003 approval. (priority)
Erlotinib hydrochloride
(Tarceva), a non-small-cell lung cancer
treatment, can be used in combination with gemcitabine for the
first-line treatment of patients with locally advanced pancreatic
cancer that cannot be removed surgically or that has spread.
(priority)
Temozolomide (Temodar)
can be used along with radiotherapy to treat patients with newly
diagnosed high grade brain tumors and then as maintenance treatment.
(priority)
Letrozole (Femara) can
be used to help treat postmenopausal women with
hormone-receptor-positive early breast cancer. The drug, an
inhibitor of estrogen synthesis, was originally approved for
treating the late stage of the disease. (priority)
People with heart disease
Candesartan cilexetil (Atacand),
a high-blood pressure treatment first approved in 1998, received two
new indications. It can be used to treat heart failure in patients
with left ventricular systolic dysfunction to reduce cardiovascular
death and to reduce hospitalizations for heart failure and to treat
heart failure to reduce the risk of death from cardiovascular causes
and to reduce hospitalizations for heart failure.
(priority)
Perindopril erbumine (Aceon),
a high-blood pressure treatment, can be used in patients with stable
coronary artery disease to reduce the risk of cardiovascular
mortality or non-fatal myocardial infarction. (priority)
People with other conditions
Fluocinolone acetonide
(Derma-Smoothe/FS) ear drops can be used
to treat chronic eczematous external inflammation of the ear.
(priority)
Infliximab (Remicade),
a treatment for the inflammation of the gastrointestinal tract known
as Crohn’s disease, has a new indication for the treatment of
patients who have moderately to severely active ulcerative
inflammation of the colon and who have had an inadequate response to
conventional therapy. (priority, biologic)
Ropinirole hydrochloride (Requip),
a Parkinson’s disease therapy, can be used for restless legs
syndrome, which is characterized by an urge to move the legs usually
accompanied or caused by uncomfortable and unpleasant leg
sensations. (priority)
Pediatric new or expanded uses
Drugs with new or
expanded uses in children approved
under priority review required by the Best Pharmaceuticals
for Children Act.
Antimicrobial Resistance
Drug-resistant bacteria continue to be a major threat to the
public health. We continued our antimicrobial resistance education
campaign partnership with the Centers for Disease Control and
Prevention and jointly released two new print public service
announcements—one English and one Spanish. In addition to the print
public service announcements, a Spanish-language brochure also was
produced.
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Date created: August 18, 2006 |