Last year, the Food and Drug Administration approved a large number of drugs,
biological products and medical devices, many of which represent a impressive
advance in the prevention, diagnosis and treatment for serious and life-threatening
Groups that particularly benefit from the 160 approved medications and medical
devices include patients with cancer, children, women, patients with heart disease
and the elderly. In addition, FDA's approvals in calendar year 2000 strengthened
the surgical armamentarium with several state-of-the-art devices that reduce
the risks of complex surgical procedures.
In addition to approving a host of important new medical products in 2000,
FDA has continued to exceed virtually all of its performance goals under the
Prescription Drug User Fee Act (PDUFA). In Fiscal Years 1999 and 2000, FDA reviewed
100% of new molecular entities (NMEs, or products with ingredients never before
marketed in the United States) within their PDUFA goal dates.
Last year, FDA approved 20 products classified as priority drugs -- drugs that
have a real benefit beyond existing therapies -- in the median time of 6 months.
Moreover, although PDUFA goals specify review times and not approval times,
actual approval times have decreased substantially since the program started.
Review times denote time FDA spends on an application, while approval times
include the time it takes for the applicant to respond to FDA's questions and
The most important products that passed the FDA's rigorous review for safety
and effectiveness last year include the first drug of a new class that addresses
an emerging serious public health threat by providing treatment of vancomycin-resistant
bacterial infections; a promising new surgical system that incorporates cutting-edge
robotics technology; and the first treatment that slows down the progress of
a disease that blinds one million Americans each year.
Another notable attribute of last year's results was an unsually high number
of pediatric products, which include the first product to treat juvenile rheumatoid
arthritis, the first vaccine for meningitis and bacteremia for infants and toddlers;
a new drug for children with influenza; and a brand new fetal monitoring system.
In addition, 13 products for a wide spectrum of diseases have been approved
for pediatric use. In recent years, Congress and FDA have been stimulating increased
pediatric submissions by offering limited pediatric exclusivity to manufacturers
who conduct studies for pediatric use of their products.
Listed below are examples of the newly approved products and their potential
benefits for various groups of patients:
Cancer patients: Several products approved last year contributed to
the prevention, early diagnosis or treatment of cancer, the second deadliest
disease in the United States and one that affects eight million Americans.
Three of these products are medical devices. One of them, the Optical Biopsy
System, is a laser system that improves a physician's ability to distinguish
small harmless growths from pre-cancerous growths in the colon. It is operated
through an endoscope and can be used to evaluate polyps less than 1 cm in diameter.
Another advanced technology for early cancer diagnosis is the Senographe 2000D,
the first mammography system that produces digital images on a solid state receptor
instead of analog images on a radiographic film.
Unlike radiographic film, digital images can be electronically stored and transfered,
so that they can be evaluated by a specialist at a remote location. The images
also can be manipulated to correct for under- or over-exposure. Early diagnosis
remains the best weapon against breast cancer which annually affects 185,000
women, 46,000 of whom die of the disease.
The third new device in this category, the FocalSeal-L Surgical Sealant, was
approved for sealing air leaks in lungs following the removal of cancerous tumors.
The sealant, which is "painted" on the lung and activated by light, was reviewed
by FDA on an expedited basis because of its potential importance for patients
with lung cancer.
Among the new cancer medications, two -- Trisenox and Mylotarg -- were approved
for cancers of the white blood cells. Trisenox (arsenic trioxide) was found
to be safe and effective for the treatment of acute promyelocytic leukemia (APL)
in patients who have not responded to, or have relapsed following, all trans-retinoic
acid and anthracycline-based chemotherapy. Trisenox, a priority drug, was approved
in six months. The product's total development time for this use was only 3
Mylotarg was approved for the treatment of CD33 (an antigen on certain leukemia
cells) positive acute myeloid leukemia for patients 60 years or older who have
relapsed for the first time and are not suitable candidates for the standard
but poorly tolerated cytotoxic therapy.
Nolvadex (tamoxifen citrate), a marketed oncological drug, was approved last
year for a new indication of particular significance for women. The drug was
approved for use to reduce the risk of invasive breast cancer for women with
preinvasive cancer of the ducts.
Other FDA approvals designed to benefit cancer patients included Pacis (BCG
Live) for the treatment of cancer-in-situ in the absence of associated invasive
cancer of the bladder; Actimmune (interferon gamma-1b) for delaying time to
disease progression in malignant osteopetrosis; and Camptosar (irinotecan hydrochloride),
which was approved for a new indication as a first-line therapy in combination
with 5-fluorouracil and leucovorin (5-FU/LV) to treat metastatic colorectal
cancer, a disease that strikes an estimated 130,000 Americans a year. The combination
showed a clear survival advantage compared to 5-FU/LV alone.
Children and infants: Several new products approved last year for pediatric
and obstetric use were either specifically designed for the youngest patients
or were adult drugs with pediatric indications. FDA also approved pediatric
use for 13 adult medications that were already on the market.
One new obstetric product is the OxiFirst Fetal Oxygen Saturation Monitoring
System, which represents the first major technological development in fetal
monitoring in three decades. The system, which builds on pulse oximetry technology,
measures oxygen saturation in the baby's blood as a sign of fetal health during
labor and delivery.
Another product of benefit to the youngest children is Prevnar, the first multivalent
conjugate pneumococcal vaccine for infants and toddlers under the age of two.
Prevnar was approved to prevent invasive pneumococcal diseases that can cause
brain damage, and, in rare cases, death.
The vaccine was designed to prevent invasive diseases caused by Streptococcus
pneumoniae, including bacteremia, an infection of the blood stream that
affects about 35,000 infants and toddlers in the U.S., and meningitis, an infection
of the lining of the brain or spinal cord that is diagnosed in about 17,500
infants a year.
One- to eight-year old children with asthma can benefit from last year's approval
for Pulmicort Respules (budesonide inhalation suspension). The product is the
first anti-inflammatory corticosteroid formulated for inhalation using a nebulizer
in this age group. This is an important feature because toddlers frequently
cannot use metered-dose inhalers.
Another new pediatric drug is Relenza (zanamivir) for the treatment of uncomplicated
influenza A and B in patients 7 years and older. Tamiflu (oseltamivir phosphate)
oral suspension was approved for prophylaxis of influenza virus in adults and
adolescents aged 13 years and older. Influenza causes 20,000 deaths and 100,000
hospitalizations a year.
Drugs approved last year that had both adult and pediatric indications included
Kaletra, Unithroid and Protopic.
Kaletra, a combination of lopinavir and ritonavir, received accelerated approval
as a protease inhibitor for the treatment of HIV, the human immunodeficiency
virus that causes AIDS.
Unithroid (levothyroxine sodium), a thyroid replacement drug, is the first
single-ingredient oral levothyroxine product approved for the treatment of hypothyroidism,
a disease that causes mental and physical sluggishness, including stunted growth.
Protopic (tacrolimus) is an ointment for patients with moderate or severe
eczema for whom standard eczema therapies present potential risks, or who are
not adequately treated by or do not tolerate standard eczema therapies.
In addition, FDA last year added pediatric use to the labeling of 13 adult
drugs including ibuprofens Motrin and Advil, Zantac (ranitidine) for stomach
acid reflux, and Nasalcrom (cromolyn) for asthma and hay fever. The agency also
approved lowering the age for the Nucleus 24 Cochlear Implant from 18-month-old
to 12-month-old infants who are profoundly hearing impaired.
Women: In addition to the Senographe and Nolvadex, discussed above,
FDA approved several other products to treat diseases that either exclusively
or predominantly affect women.
For example, Remicade (inflixmab) was approved for the reduction in signs and
symptoms of rheumatoid arthritis in patients with inadequate response to methotrexate.
Three-quarters of the more than 8 million Americans with rheumatoid arthritis
Another approval that primarily benefits women was for Novantrone (mitoxantrone
hydrochloride), a cancer drug, for the treatment of advanced or chronic multiple
sclerosis. The disease affects up to 350,000 Americans, 66-75 percent of them
In addition, FDA approved Mifeprex (mifepristone) for the termination of pregnancy
within 49 days from the beginning of the last menstrual period. The agency also
allowed continued marketing of two types of saline-filled breast implants that
had been approved for breast augmentation and breast reconstruction in women
18 years or older. The implants decision was made following the conclusion of
clinical studies involving 9,000 women.
Cardiac patients and the elderly: Examples of new products for patients
with heart disease and the elderly include several novel devices and important
Two of the devices are Cordis Checkmate System and Novoste Beta-Cath
System, both of which use catheters to deliver radiation inside a coronary stent
following the reopening of a blocked artery. The radiation helps reduce the
risk of new tissue growth inside the coronary stent and the resulting repeated
narrowing of the artery.
Another noteworthy new product for people with heart disease is TNKase (tenecteplase),
a tissue plasminogen activator produced by recombinant DNA technology. The product
was approved for the reduction of mortality in acute myocardial infarction,
the major cause of sudden death in adults, which affects more than 350,000 Americans
Among the products designed primarily for the elderly, Visudyne (verteporfin
for injection) is of particular importance as the first therapy to slow vision
loss in people with the classic type of "Wet Age-Related Macular Degeneration."
The disease causes each year blindness of 1 million Americans over the age of
In 2000, FDA also approved the Vibrant Soundbridge, a new type of surgically
implanted hearing device, for use in adults with moderate to severe nerve hearing
loss who cannot be helped by hearing aids or cochlear implants. About 20% of
Americans -- more than 56 million -- experience some nerve deafness by the age
Other significant approvals of last year included a variety of novel
drugs, biological products and medical devices. Here are several examples:
Zyvox (linezolid), the first antibacterial drug in a new class, was approved
to treat infections associated with Enterococcus faecium resistant to
vancomycin, which for many years has been the treatment of last resort for this
Zyvox was approved for treatment of bloodstream infection, hospital-acquired
pneumonia and complicated skin and skin structure infections, and for treatment
of community-acquired pneumonia and uncomplicated skin and skin structure infections.
These infections are often resistant to multiple antibiotics, and particularly
endanger hospitalized or immuncompromised individuals.
Cipro® (ciprofloxacin), an antimicrobial product, was designed to reduce
the incidence or progression of inhalational anthrax following exposure to Bacillus
anthracis. Inhalational anthrax is an extremely rare disease, usually resulting
in industrial setting from exposure to contaminated animal hides and hairs,
but the causative organism can be used as a biological weapon.
The Da Vinci Surgical System, a first-of-a-kind robotic device, enables a surgeon
to perform laparoscopic gall bladder and reflux disease surgery while sitting
at a console with a computer and video monitor and manipulating three robotic
arms with hand grips and foot pedals. The product is regarded as the forerunner
of new robotic devices that eventually may revolutionize the practice of surgery.
Trufill n-BCA Liquid Embolic System, a new glue for use in a rare form of brain
surgery that is performed when the blood vessels in the brain are intertwined.
The glue, which is infused via a catheter before surgery, helps reduce the loss
of blood by blocking blood vessels in the brain, thereby lessening the patient's
risk of stroke and death.
Apligraf, a cellular, bi-layered skin substitute to be used as a new type of
wound dressing to help heal diabetic foot ulcers. Open foot sores lead to thousands
of amputations each year in people with diabetes.
Myobloc (botulinum toxin type B), the first drug to reduce the severity
of neck and shoulder muscle contractions and the resulting abnormal head position
and neck pain associated with cervical dystonia. Treatment with the product
interrupts the cholinergic transmission between the nerve and the affected muscle,
causing it to relax.
Malarone, a new combination drug for the prevention and treatment of acute,
uncomplicated P. falciparum malaria. A combination of atovaquone and
proguanil hydrochloride, Malarone has been shown to be effective in regions
where the disease has become resistant to other anti-malarial drugs.
OssaTron, a device that uses shock waves to relieve chronic severe heel pain
when conventional treatment has been ineffective. The pain is usually caused
by an inflammation of the foot's tissue.
FDA also approved Positron Emission Tomography (PET) F-18 FDG drug as part
of an initiative under the FDA Modernization Act of 1997, which included consultations
with the public and FDAís advisory committee, a review of literature and an
FDA Federal Register notice describing how the drug could be found to be safe
and effective for certain indications. F-18 FDG is a radiopharmaceutical drug
thatís injected in patients to localize areas with abnormal glucose metabolism
to assist in cancer assessments and in identifying reversible cardiac dysfunction.
FDA performance. The products described in this report are only a small
sample of the 160 new drugs, biological products and medical devices the agency
approved last year. The approval statistics also do not reflect the many other
ways in which the Center for Drug Evaluation and Research (CDER), the Center
for Biologics Evaluation and Research (CBER), and the Center for Devices and
Radiologic Health (CDRH) strengthen public health protection.
These activities include refusal of products not shown to be safe and effective;
assuring adequate labeling for products that are approved; and monitoring the
effects of marketed drugs. Last year, the three Centers also issued 125 draft
and final guidances and other documents to clarify their requirements and facilitate
industry's compliance with FDA's demanding standards.
During calendar year 2000, CDER took 238 actions on original new drug applications.
Ninety-eight of them were approvals, which were completed in the total median
time (including FDA's review and the sponsor's response, if any) of 11.2 months.
All but two of these new drugs were processed under PDUFA, which was passed
in 1992 and which was reauthorized for five more years in 1997.
In addition to the 20 products classified as priority and approved in the median
time of 6 months, FDA approved 27 new molecular entities in the median total
time of 15.6 months. Ninety-six percent of the NMEs and 98 percent of all new
drugs were approved within their goal dates. The Center also approved eight
medications for rare diseases covered by the Orphan Drug Act of 1983.
In addition, CDER received 365 applications for the approval of generic counterparts
of original drugs. The Center issued 244 approvals and 61 tentative approvals
for such products as Doxazosin Mesylate, the generic equivalent of Cardura for
benign prostatic hyperplasia; Paclitaxel, the equivalent of the cancer drug
Taxol; and Nifedipine, the equivalent of Adalat CC for hypertension.
CBER again met all of its obligations under PDUFA. The Center took 53 actions,
resulting in 13 approvals for product license or biological license applications
(PLA/BLAs) in the median time of 25.1 months. Six of the approvals were part
of the PDUFA program, and their median approval time was 24.5 months. The 2000
cohort included one priority product, which was approved in 8.5 months.
CDRH in calendar year 2000 took 285 actions on original devices submitted for
full evaluation under Product Marketing Applications (PMAs). Forty-nine PMAs
were approved in the median approval time of 9.6 months, and four additional
products were approved under FDA's Humanitarian Use Exemptions program for devices
with a patient population of up to 4,000. These devices were approved in the
median time of 3.5 months. In addition, the Center cleared for the market 3,457
so-called 510(k) devices, products that are similar to devices already in use.
These notifications were reviewed in the median total time of 2.4 months.
In January 2000, CDRH took over from the Centers of Disease Control and Prevention
the responsibility for the implementation of the Clinical Laboratory Improvement
Amendments (CLIA) of 1988, which establishes quality standards to ensure the
accuracy, reliability and timeliness of laboratory test results for patients.
In addition to evaluating laboratory tests for marketing, the Center categorized
1,058 diagnostic tests according to the potential risk to public health, and
allowed 158 tests to be conducted in any setting.