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About CDER - Report |
U.S. Food and Drug Administration • Center for Drug Evaluation and Research |
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About CDER - Report |
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CDER Report to the Nation: 2002 Adobe Acrobat version of this document 1 Drug ReviewIndex
MissionWe 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. HighlightsMany Americans benefited from last year's timely reviews of new prescription medicines, over-the-counter medicines and the generic equivalents for both. We approved 17 new medicines that have never been marketed before in this country, known as new molecular entities. We approved 321 generic versions of existing drugs. We authorized 13 medicines to be sold over the counter without a prescription, and 11 of them can be used by children. We met or exceeded 12 of the 14 performance goals for the fiscal year 2001 receipt cohort, the latest year for which we have full statistics. These are goals we agreed to under legislation authorizing us to collect user fees for drug reviews. In addition to surpassing all goals for original new drug applications, we exceeded all three of the goals for new molecular entities. We conducted 487 foreign and domestic inspections that help protect volunteers for clinical trials from research risks and validate the quality and integrity of data submitted to us. Highlights of new medication options for American consumers include:
Drug approvals for 2002
New Drug ReviewReview 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. Our charts show these 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. 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. Filings provide an idea of what the workload in subsequent years will be. Priority new drugs (N=NME)We took 18 actions on priority new drug applications, of which 11 were approvals. These drugs represent significant improvements compared with marketed products. We have a goal of reviewing 90 percent of these applications within six months. The 2002 priority new drug approvals were:
New molecular entitiesSeventeen of the new drugs we approved were new molecular entities, and seven received priority reviews. NMEs contain an active substance that has never before been approved for marketing in any form in the United States. The 2002 NME approvals were:
Orphan drugs (N=NME)Eight of the approvals were for "orphan" uses in patient populations of 200,000 or fewer. Sponsors of such products receive inducements that include seven-year marketing exclusivity, tax credit for the product-associated clinical research, research design assistance by FDA and grants of up to $200,000 per year. The 2002 orphan new drug approvals were:
New Drug Review StatisticsLast year saw a steep rise in median total approval times for priority NDAs and NMEs. This was a statistical artifact caused by the approval of a number of older applications remaining from the 1999 and 2000 receipt cohort coupled with a significant decrease in the number of priority applications received in 2001 and 2002. With a smaller pool of recent priority applications with short approval times, the remaining "tail" of submissions for earlier years dominated the median approval time statistic. Internet resources for drug review statisticsOther drug review statistics are available on our Web site at http://www.fda.gov/cder/rdmt/default.htm. Reasons for approval delays studiedWe examined reasons for approval delays on first cycle reviews for standard and priority new molecular entities in 2000 and 2001. Standard NMEs:
Priority NMEs:
Priority new drug statistics
Priority new molecular entity statistics
Standard new drug statisticsWe took 154 actions on standard new drug applications, of which 67 were approvals. These drugs have therapeutic qualities similar to those of already marketed products. We have a goal of reviewing 90 percent of these applications within 10 months. Standard NDA statistics for 2002 include:
Standard new molecular entity statistics
Notable 2002 new drug approvalsLast year's approvals benefited people with cancer, HIV infection, heart disease and other disorders. People with cancerOxaliplatin for injection (Eloxatin) is used with infusional 5-FU/LV to treat cancer of the colon or rectum in patients whose disease has recurred or progressed during or within six months of completion of first-line therapy. Fulvestrant (Faslodex) is for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. People with gastrointestinal disordersTegaserod maleate (Zelnorm) is the first drug approved for the short-term treatment of women with irritable bowel syndrome whose primary bowel symptom is constipation. The medicine is the first agent in a new class of drugs called serotonin-4 receptor agonists (5HT4 agonist) developed to target the gastrointestinal tract. People with heart diseaseEplerenone (Inspra) treats high blood pressure both alone and in combination with other antihypertensive therapies. The drug works by selectively blocking aldosterone, a hormone that plays a role in regulating electrolyte and water balance. An imaging agent, dimyristoylphosphatidylcholine and perflexane (Imagent Kit for the Preparation of Perflexane Lipid Microspheres), can help in the diagnosis of heart disease. It is intended for use in patients with suboptimal ultrasound images of the heart. It helps distinguish between normal and abnormal heart structure and motion, two primary indicators of cardiac health. Olmesartan medoxomil (Benicar) treats high blood pressure. People with pulmonary hypertensionTreprostinil sodium (Remodulin) is a continuous subcutaneous infusion for the treatment of pulmonary arterial hypertension, a disease in which blood pressure in pulmonary arteries rises to life-threatening levels. The orphan priority drug received accelerated approval. People needing dialysisIcodextrin (Extraneal) is a peritoneal dialysis solution that expands patients' options for effective fluid management in home-based peritoneal dialysis, a form of kidney dialysis. Infectious diseasesAdefovir dipivoxil (Hepsera) is the first nucleotide analogue to be approved for the treatment of chronic hepatitis B. Voriconazole (Vfend) is a triazole antifungal agent indicated as the primary treatment for acute invasive aspergillosis and as a salvage treatment for rare but serious fungal infections. It is available in both oral and intravenous formulations. Ribavirin (Copegus), in a new formulation, received a priority review for treatment of hepatitis C. People with mental illnessAripiprazole (Abilify), which is administered as a once-daily oral tablet, was shown in clinical studies to provide significant improvements in both the positive and negative symptoms of schizophrenia. People with neurological disordersSodium oxybate (Xyrem), an oral solution, is the first drug approved for the treatment of cataplexy, a sudden loss of muscle tone associated with narcolepsy. The medicine is a Schedule III controlled substance. Eletriptan hydrobromide (Relpax) acts on blood vessels and sensory nerve endings to relieve the symptoms of migraine attacks. Pediatric usesAtomoxetine sodium (Strattera) is the first major new treatment for attention-deficit/hyperactivity disorder in three decades. The drug works to prolong the presence in the brain of the chemical norepinephrine, which is involved in regulating attention and impulsivity levels. It provides full-day relief of symptoms without causing insomnia in most children and adults. It is the first drug approved to treat the condition in adults. Nitazoxanide (Alinia), a priority orphan approval, is the first oral suspension medicine specifically approved for the treatment of diarrhea caused by two parasitic infections, cryptosporidiosis and giardiasis in children 1 to 11 years old. In compromised children, these infections have been associated with malnutrition and impaired growth. Nitisinone (Orfadin), a priority orphan approval, is used to treat hereditary tyrosinemia type I, a life-threatening metabolic disorder that affects fewer than 100 children the United States. The disease, which results from the lack of an enzyme to break down the amino acid tyrosine, usually results in progressive liver disease and liver cancer. Office-based addiction treatmentBuprenorphine hydrochloride (Subutex) and the combination of buprenorphine and naloxone (Suboxone) treat opiate addiction by preventing symptoms of withdrawal from heroin and other opiates. These orphan drugs are the first treatments of opiate dependence that can be prescribed in an office setting under the Drug Addiction Treatment Act of 2000. Chemical warfare antidoteAtropine and pralidoxime chloride (ATNAA), sponsored by the U.S. Army, is for use as an antidote to nerve agent exposure. People with eye diseaseCyclosporine (Restasis), in a new ophthalmic emulsion formulation, received a priority review for treatment of moderate to severe inflammation of the eye's cornea and to restore and maintain normal tear secretion and surface integrity of the eye. New or Expanded Use ReviewApplications 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. The new and expanded use review statistics on this page include figures for both priority and standard applications. Priority and standard application review performance will be reported separately in the future to reflect better their different review goals. Statistics on new or expanded uses (efficacy supplements)
Priority efficacy supplement reviews
Orphan new or expanded uses
Notable 2002 new or expanded use approvalsAnastrozole (Arimidex Tablets) is for adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer. Argatroban (Argatroban Injection), an anticoagulant, is for use in patients undergoing heart catherizations and have or are at risk for developing heparin-induced decreases in the number of blood platelets. Clopidogrel bisulfate (Plavix), a blood thinner, is now approved to treat acute coronary syndrome. Clozapine (Clozaril) can be used to treat patients with schizophrenia or schizoaffective disorder who are at risk for emergent suicidal behavior. Imatinib mesylate (Gleevec) is for treatment of gastrointestinal stromal tumor, which affects about 5,000 people in the United States each year. It is a tumor that generally arises within the stomach or intestinal tract and metastasizes within the abdomen or the pelvis. The drug was first approved in May 2001 for treatment of Philadelphia chromosome positive chronic myeloid leukemia. Irbesartan (Avapro) and losartan potassium (Cozaar) can be used to treat kidney damage in people with Type 2 diabetes. Both belong to a class of high blood pressure drugs known as angiotensin II receptor blockers. Latanoprost ophthalmic solution (Xalatan) is for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Secretin (SecreFlo for Injection), used for secretin stimulation testing, received two approvals for identification of pancreatic disorders. Zoledronic acid (Zometa) is for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard therapy. Irritable bowel syndrome treatment reintroducedAlosetron hydrochloride (Lotronex), a treatment for diarrhea-predominant irritable bowel syndrome in women that had been withdrawn for safety reasons in 2000, was reintroduced with limited distribution and a risk management plan. The regulatory mechanism for reintroduction was a priority efficacy supplement. Priority pediatric labeling changesWhen studying approved drugs in children, sponsors often learn new information about the drug's safety and the doses that should be used. An efficacy supplement changes the labeling information to reflect the new discoveries, even if there is not a new or expanded use. Consistent with the mandate in the Best Pharmaceuticals for Children Act, these pediatric supplements received priority reviews last year:
Other pediatric exclusivity priority reviewsVinorelbine tartrate (Navelbine) is a cancer treatment, and pediatric clinical trials are now described in the labeling. Pediatric Drug DevelopmentLast year, we approved 19 labeling changes for pediatric uses. Also, we approved three new molecular entities (above). As of April 1, 2003, we had received 328 proposed pediatric study requests from manufacturers, issued 272 written requests, made 84 exclusivity determinations and added pediatric use information to 50 labels. The Best Pharmaceuticals for Children Act of 2002 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. It also allows us to collect user fees for reviewing these pediatric supplements and mandates a six-month priority review for a pediatric supplement submitted in response to a written request. The law also authorizes the National Institutes of Health to contract for pediatric studies for drugs that lack patent protection or other marketing exclusivity, referred to as "off-patent" drugs. In consultation with us, the NIH obtained input from outside pediatric experts to identify the priority off-patent drugs for which pediatric studies are needed. A list of 12 of these drugs was published in January 2003, and contracts for testing them will publish later in 2003. Pediatric exclusivity has helped us uncover important dosing and safety information, such as drug effects on growth, to help healthcare providers use drugs to treat children more confidently. The absence of pediatric testing and labeling poses significant risks for children. Children may be exposed to ineffective treatment through underdosing. Inadequate dosing information exposes children to the risk of adverse reactions without the benefit of efficacy; however, overdosing may pose greater risk of adverse reactions. Young patients may not benefit from therapeutic advances because physicians choose to prescribe existing, less effective medications in the face of insufficient pediatric information about a new medication. The failure to produce drugs in dosage forms that can be used by young children such as liquids or chewable tablets can also deny them access to important medications. Pediatric Rule thrown out; clearer authority soughtIn October 2002, the U.S. District Court for the District of Columbia ruled that we lacked legislative authority to issue our Pediatric Rule and has barred us from enforcing it. The government decided not to pursue an appeal and will work with Congress to pursue legislation requiring drug manufacturers to conduct appropriate pediatric clinical trials. Conditions with approved pediatric labeling
Internet resourcesOur Web site for up-to-date pediatric labeling changes is at http://www.fda.gov/cder/pediatric/index.htm.
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