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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: 2001 Drug Review (continued)Index
Over the Counter Drug ReviewIn 2000, we approved six new drugs and one new use for over-the-counter marketing.
New OTC medicines and new usesMiconazole nitrate (Monistat 3) is to treat vaginal yeast infections and external itching associated with a vaginal yeast infection. This is not the first OTC approval for this compound. Miconazole nitrate (Monistat 1). This is a one-day treatment regimen vs. a three-day treatment regimen under Monistat 3 (above) and a seven-day treatment regimen under Monistat 7. The combination clemastine fumarate, pseudoephedrine hydrochloride and acetaminophen (Tavist A/S/H) treats symptoms of hay fever and other seasonal allergies. This is the first approval for this combination but not the first time for any of these compounds on the OTC market. Chlorhexidine gluconate and ethyl alcohol (Avagard-CHG) is for use as a surgical hand scrub or hand wash for healthcare personnel. This is not the only chlorhexidine product available OTC. Aspirin, 500 mg, (Bayer Extra Strength Aspirin for Migraine Pain) is for the treatment of migraine headaches. This represents a new OTC use for aspirin. A cream with 1 percent butenafine hydrochloride (Lotrimin Ultra) is an Rx-to-OTC switch for the use of this drug product to treat jock itch, athlete's foot and ringworm. A nasal spray containing cromolyn sodium (Nasalcrom) is now approved for OTC use down to 2 years of age. Improved labels for OTC medicinesAmerican consumers are benefiting from easy-to-understand labels on drugs they buy without a prescription. Titled "Drug Facts," the new labels become mandatory in May 2002. These new labels improve a consumer's ability to use an OTC drug safely and properly and to find and understand its benefits and risks. Public meeting airs OTC antihistamine issuesA citizen's petition submitted in 1997 asked us to consider switching the antihistamines loratadine, fexofenadine and cetirizine to OTC marketing status. Last year, our advisory panel of outside experts concluded that these drugs would be a reasonably safe alternative for consumers to treat nasal symptoms of seasonal and nonseasonal allergies. We and the manufacturers are considering their recommendation. How we regulate OTC drugsWe 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 can also be approved for OTC sale through the new drug review process. Generic Drug ReviewWe received 320 submissions and approved 234 generic drug products in 2001, including 40 separate molecules in 55 products that represent the first time a generic drug was available for the brand-name product. The median approval time for generic drugs was 18.1 months. We are making changes to decrease the overall time to approval of applications. The median statistic for total approval time has hovered at about 18 to 19 months for five years. Planned changes include several efficiencies in the review process and hiring of additional chemistry reviewers.
Generic drug statistics
Tentative approvals
Generic drug Web siteYou can find more information about our generic drug program at http://internet-dev.fda.gov/cder/ogd/index.htm. Notable 2001 generic drug approvalsExamples of first-time approvals for the brand-name equivalent are:
Our approval of generic versions of these drugs last year could save American consumers and the federal government hundreds of millions of dollars each year. We also issued 73 tentative approvals and 13 approvables last year:
Building consumer confidence in generic drugsTo promote consumer confidence in the safety and effectiveness of generic drugs, we are developing a multimedia education program. The goal will be to educate health care practitioners and consumers about the rigorous review and approval process that generic products undergo before we approve them for sale in this country. We are creating partnerships and a network with other government agencies. The efforts will include:
Generic drug electronic submissionsThe electronic submissions initiative is a continuing priority. We developed and issued a draft guidance on a standardized format for application submission that will be compatible for both new drug and generic applications. This should promote industry participation in the program. How we approve generic drugsGenerics are not required to repeat the extensive clinical trials used in the development of the original, brand-name drug. Instead, they must show bioequivalence to the brand-name reference listed drug. Scientists measure the amount of the generic drug that reaches the bloodstream and how long it takes to get there. This rate and extent of absorption is called bioavailability. The bioavailability of the generic drug is then compared to that of the brand-name reference listed drug. The generic version must deliver the same amount of active ingredients into a patient's bloodstream and in the same time as the brand-name reference listed drug. Brand-name drugs are subject to the same bioequivalency tests as generics when their manufacturers reformulate them. User Fee ProgramWe met all of the demanding review goals of the Prescription Drug User Fee Act for applications submitted in fiscal year 2000, the latest year for which there are meaningful review statistics. We are on track for meeting them in fiscal year 2001. The law, first enacted in 1992, was renewed for an additional five years in 1997. Under the law, the drug industry pays user fees for new drug applications, efficacy supplements and some other activities. User fees helped us hire additional scientists to perform reviews. As a result, we are able to respond more rapidly to new drug applications without compromising review quality. That means more quality drug products are reaching American practitioners and consumers more quickly. We agreed in 1992 to specific performance goals for the prompt review of four categories of submissions: original new drug applications, resubmissions of original NDAs, efficacy supplements to already approved marketing applications and manufacturing supplements to already approved new drug marketing applications. With the 1997 reauthorization, known as PDUFA II, we committed to additional goals intended to improve our responsiveness to and communication with industry sponsors during the early years of drug development. These goals specify timeframes for activities such as scheduling meetings and responding to various sponsor requests. While the intent of the 1992 law was to speed up the review process, the intent of PDUFA II is to speed up the entire drug development process. We have encountered challenges in trying to meet the PDUFA II goals. The fees we collected have been significantly less than expected due to a reduced number of new drug applications and an increased proportion of submissions whose fees were exempted or waived. At the same time, the number of goal-driven tasks for which we collect no fees increased substantially under PDUFA II. So far we have been able to meet most of our performance goals. Our efforts to meet the PDUFA II goals may have had an unintended impact on approval times of standard new drug applications. These approval times have begun to increase because more applications require multiple review cycles to reach approval. This may be due to the fact that reviewers have been pressed to meet the additional PDUFA II goals for drug development, such as meeting management, special protocol assessments and responses to clinical holds. Reviewers have had less time for resolving last-minute problems with these standard applications before the action goal date. Such applications must undergo an additional review cycle with its attendant timeframes and goals. Statistics on this trend are preliminary, and we are watching it closely. User fee reportOur full report to Congress on our user fee performance is at http://www.fda.gov/oc/pdufa/report2001/pdufareport.html. User fee review goalsUnder PDUFA II, our review goals continued to shorten. By fiscal year 2002, the goals called for us to review and act on 90 percent of:
Manufacturing Supplement ReviewWe review many types of changes in the manufacturing of drugs and their packaging, including location, machinery, processes and suppliers of raw materials. We do this so that American consumers can trust the high quality of FDA-approved medicines. Manufacturers notify us in advance of certain manufacturing changes. These are known as "manufacturing supplements" to new drug or generic drug applications. In many cases, they represent the industry's efforts to modernize plants and equipment or to make manufacturing more efficient
New drug manufacturing supplements
Generic drug manufacturing supplements
Antimicrobial ResistanceThe emergence of drug-resistant bacteria is considered to be a major threat to the public health. We play an active role in the federal government's efforts to address this growing problem and its effects on drug development and regulation. We are developing approaches to provide education and information on the appropriate use of antibiotics to health care professionals and consumers. Details of our efforts and other resources are at http://www.fda.gov/cder/drug/antimicrobial/default.htm. Electronic SubmissionsCurrently, the entire archival copy of the new drug application, postmarketing safety reports and advertising and promotional material can be submitted in electronic format without paper. We find submissions provided electronically as described in our guidance documents both easier to process and more efficient to review. While the number of electronic submissions continues to increase each year, only 15 percent of supplements and amendments are submitted in electronic format. Over the next year, we look to industry to increase the number of electronic-only submissions. Over the past year, we have worked on and begun evaluating electronic submission projects that will:
We also are working on the ability to accept the following documents in electronic format:
Pregnancy labelingWe have reviewed the current system of labeling drugs for use by pregnant women and are developing an improved, more comprehensive and clinically meaningful approach. We are consulting with multiple government agencies, medical experts, consumer groups and the pharmaceutical industry to develop this new labeling format. Assessing Data Quality, Research RisksTo protect the rights and welfare of volunteers and verify the quality and integrity of data submitted for our review, we perform on-site inspections of clinical trial study sites, institutional review boards, sponsors, study monitors and contract research organizations. 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. When obtaining data about the safety and effectiveness of drugs, sponsors rely on 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, including manufacturers, institutional review boards, study sponsors, clinical investigators and their staffs, monitors, contract research organizations, hospitals and other institutions. Sponsors and clinical investigators protect volunteers by ensuring that:
Special attention is given to protecting vulnerable populations, such as children, the mentally impaired or 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.
Inspections of clinical research in 2001We conducted a total of 463 inspections of clinical research:International inspections of clinical researchWe have conducted 457 inspections of clinical research in 47 countries from 1980 to 2001. 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. These efforts include our work with the International Conference on Harmonization and the Declaration of Helsinki. Top 5 deficiency categories for clinical investigator inspections
Drug Review TeamWe use project teams to perform drug reviews. Team members apply their individual special technical expertise to review applications:
Scientific training for reviewersOur systematic, internal training program in science, policy and job-related skills for reviewers is based on core competencies, learning pathways and individual development plans.
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