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A. The Approved Drug Products with Therapeutic Equivalence Evaluations, also known as the Orange Book, lists all brand name and generic drug approvals by chemical name in alphabetic order. You can access this site via the Internet at: www.fda.gov/cder/ob/default.htm.
When you arrive at this site, click on Search by Active Ingredient, type in the chemical name of the drug you need information on, then click on Submit Query. A chart will appear that lists all approved brand name and generic drugs for the chemical name that you input. To determine generic versus brand name drugs, look in Column 1 entitled, Application Number. Series 40-000, 60-000, 70-000, and 80-000 are generic drugs, and all other series are brand name drugs. Column 2 entitled, TE Code shows the therapeutic equivalence code. This code represents the FDA's coding system for therapeutic ratings of generic drugs. For a full explanation of the therapeutic equivalence codes, click on TE Code in Column 2.
In addition, the FDA has prepared a Draft Guidance for Industry entitled, Placing the Therapeutic Equivalence Code on the Prescription Drug Labels and Labeling. You can obtain a copy of this draft guidance at the following Internet address: www.fda.gov/cder/guidance/index.htm. When you arrive at this site, go to "Labeling (Draft)" and click on draft guidance number 4.
This draft guidance is intended to clarify for prescription drug manufacturers, relabelers, and distributors the FDA's position regarding placing the therapeutic equivalence code on approved FDA product labels and labeling. It also provides recommendations on how to display therapeutic equivalence codes on labels and labeling. The FDA believes that it is legally permissible to allow therapeutic equivalence codes to be placed on drug product labels and labeling. We also believe that the use of therapeutic equivalence codes will contribute to the accurate and safe selection of generic products by pharmacists.
A. Yes, prior to working on any applications, new employees are required to provide information to the FDA Ethics Branch regarding any financial interest they currently hold that may present any conflict of interest. Federal regulations prohibit all employees from participating in an official capacity in any regulatory matter in which they hold a financial interest, if the matter will have a direct and predictable effect on that interest.
A. As you know, an enormous amount of information is available on the Internet relating to drug products and treatments. It is impossible to predict what percentage of individuals will comprehend the information that they find relating to drugs; some individuals will understand what is presented and some will not. The FDA strongly encourages consumers to speak with their health care providers, medical professionals familiar with each individual's current health status and past medial history, regarding the selection of any drug product.
As the FDA has more closely examined Internet sales of drugs over the past few months, we are struck by the diversity of Internet sites and the multi-faceted nature of the issues that are presented. Questions arise about the authenticity of the information provided as well as about the quality of pharmaceutical products sold on-line at certain Internet sites. The legitimacy of some prescribing activities is also an important issue.
The FDA cannot control dissemination of drug information on the Internet unless illegal acts occur. The FDA regulates products and certain activities related to those products, particularly when carried out by or on behalf of a manufacturer, packer, or distributor. For example, current law directs FDA to help ensure that all new drugs are safe and effective. We are but one part of the current health care system in which a patient receives a prescription from a licensed prescriber and generally has it filled by a local pharmacist. The law did not foresee the emergence of a tool such as the Internet, and regulation of the Internet is a complex issue. The government doesn't want to unduly restrict such a tool, but at the same time wants to ensure protection of consumers. Currently, various federal agencies are exploring ways to maintain their consumer protection function without hindering the free flow of communication on the Internet.
The Office of Compliance in FDA's Center for Drug Evaluation and Research (CDER) reviews Web sites that consumers, industry, or health professionals report as appearing to be violative. CDER has taken a number of actions, such as sending Warning Letters to firms using the Internet to illegally promote the sale of unapproved new drugs and issuing Import Alerts on illegal foreign products sold on-line. FDA has also contacted Web site managers and asked for their voluntary cooperation in removing offensive sites. Warning letters to offshore pharmacies are shared with the firm's home government, from whom we request cooperation. Additionally, CDER's Division of Drug Marketing, Advertising, and Communications has taken steps against Internet promotion that violates the FD&C Act, for example, by making unsubstantiated claims for drugs or misrepresentations, or by a lack of fair balance in describing risks versus benefits.
Clearly, oversight of the variety of public health related activities that can occur on the Internet requires the attention not only of FDA and other Federal agencies, but also State licensing and regulatory boards, the pharmaceutical industry and health professional organizations. The Agency is in the process of developing draft guidance for industry to provide clarification on the use of the Internet for promoting regulated products and has established an internal working group to explore other areas relating to Internet sales.
A. The Agency is considering how the section 503A exemptions on pharmacy compounding will apply to homeopathic drugs and will provide information on this subject once a decision is made.
A. The new regulation, "Dissemination of Information on Unapproved/New Uses for Marketed Drugs, Biologics, and Devices," published in the Federal Register on November 20, 1998, followed the provisions included in section 401 of the Food and Drug Administration Modernization Act of 1997 (FDAMA). FDAMA specifically lists who can receive the new use information from a manufacturer. The list includes health care practitioners, pharmacy benefit managers, health insurance issuers, group health plans, or Federal or state governmental agencies. Pharmacists are not specifically mentioned in the statute. The implementing regulation contains the same list of recipients as the statute.
However, pharmacists who are included or employed by one of the listed groups could be recipients of the information. FDA does not know of any intention on the part of Congress to redefine the recipients of this information in the statute.
A. Section 115 of the Food and Drug Administration Modernization Act of 1997 (FDAMA) required the review and development of guidance on the inclusion of women and minorities in clinical trials. The FDAMA Women and Minorities Working Group was formed. This group compiled and evaluated existing FDA documents as well as other existing documents relating to enrollment of women and minorities in clinical trials. They were also asked to identify other suggested changes to comply with FDAMA. The report of the Working Group "Women and Minorities Guidance" is located at the following Website: www.fda.gov/cder/guidance/guidance.htm#Modernization Act of 1997.
The group identified the following existing documents related to the inclusion of women and minorities in clinical trials:
The group identified the following projects that when implemented will help ensure the appropriate analysis of information about the use of drugs specifically in women, ethnic and minority participation in clinical trials.
The group, after consultation with representatives from the pharmaceutical industry, as required by section 115 (b) of FDAMA, recommended that no additional guidance is needed at this time.
A. Under the Federal Food, Drug, and Cosmetic Act and its implementing regulations, advertisements for prescription drugs must contain a summary of all of the risks of the advertised product. Thus, print ads typically contain, in relatively small print often on another page from the display copy of the ad, all of the risk information from the product's approved labeling (package insert or prescribing information). In addition, advertisements must present a "fair balance" of information about effectiveness vs. information about risks. For print advertisements, this means that the most important risks of the product must be disclosed in the display copy of the ad.
For broadcast advertising, the disclosure requirement specifies that the ad must contain the most important risk information. In addition, as an alternative to the summary of all the risk information required for print advertising, FDA regulations require that "adequate provision" be made for disseminating the product's approved labeling. In August 1997, FDA issued a draft guidance suggesting four components will satisfy this requirement for dissemination of product labeling. Including in the advertisement: (1) a toll-free telephone number to obtain the approved labeling, (2) a statement that additional product information is provided with concurrently running print ads or brochures, (3) a statement that health care professionals may provide additional product information, and (4) an Internet web page address.
The regulations also require that advertisements not be false or misleading or omit "material" facts, and must present a balance of information about risks and benefits. The FDA has been applying these regulations to prescription drug print ads directed towards consumers since the late 1980's. Recently, we have closely scrutinized all broadcast ads to ensure that they comply with the regulations and have taken rapid action when the ads violate the law. This has included instances where critical information has not been communicated in language understandable to consumers.
Balanced advertisements that convey a product's approved use in a non-misleading fashion and provide sufficient information about the product's risk may help consumers to have an informed discussion with their health care provider about the product's appropriateness for them. However, FDA is examining whether the current disclosure requirements, as applied to print and broadcast advertising, provide optimal communication to consumers. FDA will also evaluate the effects of direct to consumer promotion on the public health within two years of finalizing the draft broadcast guidance.
A. FDA does not develop drugs. Pharmaceutical manufacturers develop and test drugs, both preclinically and in humans, and submit the results of that testing to the FDA for review. We are only indirectly involved in the cost of drug development insofar as manufacturers must meet FDA's regulatory requirements in the course of developing their products. FDA has been very active over the past several years in streamlining and clarifying our regulatory requirements. Our goal has been to continue to exert appropriate oversight to assure that drug products entering the marketplace are safe and effective while placing the minimum regulatory burden on drug manufacturers.
Under the Prescription Drug User Fee Act (PDUFA), FDA significantly decreased the time we take during the drug development process to review applications submitted to us for review. More recently, as a result of the Food and Drug Modernization Act (FDAMA), the Agency has further clarified a number of our regulatory requirements and taken further steps to enhance and track our interactions with the pharmaceutical industry.
Although the cost of drug development is really in the hands of the pharmaceutical industry, the FDA is committed to appropriately minimizing the regulatory burden and clearly communicating the regulatory requirements to the industry so as not to inappropriately add to the cost of drug development.
A. The Center for Drug Evaluation and Research (CDER) views all benefit to risk assessment in the context of the disease. CDER uses a number of approaches to assess risk to ensure continued safe use of all drugs, including those intended to treat patients with HIV/AIDS. These include spontaneous reporting systems to rapidly identify potential new problems; large healthcare databases with product use linked to subsequent diagnoses, hospitalizations, and other adverse events; cohort and case-control studies to investigate a specific safety issue; and registries initiated when potential risks, particularly those apparent only with long-term follow-up, are sufficient to warrant identification and active follow-up of individuals exposed to a product. Cooperative agreements and collaboration with the private sector are used to leverage FDA's internal expertise and surveillance data with formalized access to non-Agency epidemiologists and extensive databases. The goal is to have large, population-based databases to conduct studies to address safety issues of concern, even on relatively short notice. The FDA relies on multiple approaches because no single approach is sufficiently comprehensive to permit full evaluation of all problems.
In our current health care system, consumers of prescription drugs generally receive their risk information from their health care providers, including their personal physicians and pharmacists. FDA uses a number of mechanisms to assure that complete risk information is available to health care personnel. The primary mechanism is the product labeling in which all adverse events are required to be reported.
Although product labeling designed for health care professionals is the primary vehicle for communicating risk information, ensuring the widest possible distribution of new risk information is a major goal of FDA outreach. Historically, notifications produced by the Agency have included press releases, talk papers, meeting announcements, Safety Alerts, Public Health Advisories, articles, brochures and Medical Bulletins. FDA staff also make numerous presentations on medical product safety at conferences and meetings in a variety of settings.
With advances in information technology, the Agency has begun using new avenues to reach target audiences. Websites maintained by FDA contain general and specific information for designated constituencies. This information includes product approval letters, package insert text, patient package inserts (when available), Dear Healthcare Professional letters, and information on product withdrawals and recalls.
A. Benefit to risk evaluation at the time of approval is largely qualitative and contextual. That is, depending on the disease being treated, different degrees of risk are tolerated and the degree of benefit is not necessarily uniform in all cases. For example, in treating cancer a great deal of risk is tolerated for, at times, a small incremental benefit. Conversely, for a drug approved to treat simple headache, the benefit is real but the risk tolerance is very low.
With regard to the use of longitudinal studies, large simple trials (LSTs), trials that are generally much larger than the typical ones in new drug applications are designed with simplicity and easily determinable endpoints, are sometimes conducted pre- or post-approval. Although lingering safety concerns and the post-approval ongoing benefit-risk re-analyses are being investigated with LSTs more often, LSTs remain uncommon in human medical product development. Clinical trial populations still do not completely reflect the population who will be using a product once it goes on the market. We believe that the possibility of expanding the use of large, community-based simple trials designed to identify serious adverse events in a larger and more representative patient population prior to approving a product for widespread use should be broadly discussed as a public health policy issue.
A. Unfortunately, due to confidentiality rules, we cannot disclose whether there are combination studies being done until the product is approved or unless the information has already been made public. The FDA is primarily responsible for approving drug products that have been shown to be safe and effective; however, the National Institutes of Health (NIH) has established the National Center for Complementary and Alternative Medicine (NCCAM). The NCCAM's purpose is to facilitate the evaluation of alternative medical treatments. They can be reached at the following address and phone numbers:
NCCAM ClearinghouseA. The FDA is concerned about the readability and comprehension of labeling on all drug products, prescription as well as over-the-counter (OTC). The information provided in patient package inserts (PPIs) should be clearly written for the average person. FDA will not specify a reading level due to concerns about the validity of readability tests as applied to patient drug information. However, the principles of clear writing should be followed. Further discussion of this issue and references to appropriate writing manuals can be found in the proposed rule entitled "Prescription Drug Product Labeling; Medication Guide Requirements; Proposed Rule," (60 FR 44182 at 44200) that published in the Federal Register on August 24, 1995. Technical terminology should only be used if the terminology is explained and use of the terminology would help the patient understand the material. In addition, deletion or degradation of important risk, benefit, or directions for use information cannot be justified by the need for language simplification.
FDA encourages, but does not require, the dispensing of patient information in foreign languages, in low literacy formats, or in Braille for visually impaired consumers. Given the development of foreign language computer data bases, translations in other language formats may become easier to supply. However, the FDA believes that most of these populations could benefit from English language leaflets because, for example, a relative or friend could translate the information. The Medication Guide final rule (63 FR 66377) does not prohibit, in addition to English language leaflets, the distribution of materials in other languages or Braille, or materials in simplified texts, or using icons or symbols. FDA continues to believe that a multifaceted communications system would help ensure that all consumers receive meaningful patient information.
However, this final rule, which became effective on June 1, 1999, establishes requirements for the distribution of patient labeling only for certain selected human drug and biological products (certain products that pose a serious and significant public health concern) used primarily on an outpatient basis. The agency realizes that patient educational material must be written in plain language and presented in a user-friendly format in order to be useful to the consumer. Therefore, the requirements in the final rule for a Medication Guide include the following:
In addition to this rulemaking, the FDA is working with industry on a cooperative plan designed to provide consumers with better and easy-to-read information about their prescription drugs. Under the plan, useful written information must reach 75 percent of patients receiving new prescriptions by the year 2000 and 95 percent of patients by the year 2006. This plan, which was included in FDA's appropriations legislation for fiscal year 1997, parallels the requirements for the development of Medication Guides that are easily understood, non-promotional in tone and content, and scientifically accurate.
To help consumers make better decisions regarding over-the counter (OTC) medications that they select, the FDA issued a final rule on March 11, 1999 that will require new, easy to understand labeling on OTC drugs. By clearly showing a drug's ingredients, dose, and warnings, the new labeling will make it easier for consumers to understand information about a drug's benefits and risks. In addition to many other provisions, this final rule provides standardized headings and order of information in the labeling as well as simplified language for many words and phrases.
A. The Center for Drug Evaluation and Research began receiving reports of medication errors in January 1992, when the U.S. Pharmacopeia (USP) began forwarding reports to the FDA. To evaluate and recommend appropriate actions on these reports, the Medication Errors Subcommittee was formed in June 1992. This Subcommittee is no longer in existence; however, their responsibilities have been delegated to the Associate Director for Medication Error Prevention in the Office of Post-Marketing Drug Risk Assessment. In November 1993, the agency began evaluating and coding MedWatch reports for medication errors and publicly stated that physicians and other health care professionals could report medication errors directly to the FDA through the MedWatch program. These reports are then processed via the Adverse Events Reporting System (AERS), and are electronically available to CDER's safety evaluators for review.
CDER responsibilities are not completed when the safety and effectiveness of a drug product are determined. CDER also has the responsibility for helping to ensure the safe use of the drugs it approves by identifying and avoiding proprietary names that contribute to problems in the prescribing, dispensing, or administration of the product. Because early identification of a potential confusing proprietary name is crucial, CDER reviews these proposed names, prior to approval of a new drug application, by means of the Labeling and Nomenclature Committee.
In addition, CDER works closely with the Institute for Safe Medication Practices and the USP regarding medication errors.
A. In its initial efforts to implement the Dietary Supplement Health and Education Act (DSHEA) in 1994, the Agency concentrated on promulgating the many regulations mandated by DSHEA and began a number of other regulatory actions to establish a framework for implementation of the new statute. Since passage of DSHEA, FDA has published 25 Federal Register documents regarding dietary supplements. For more information on the proposed and final regulations that FDA has issued, please visit the CFSAN Website at: www.cfsan.fda.gov. Just as the Agency is committed to implementing DSHEA fully and ensuring consumers have access to dietary supplements, FDA also is committed to quickly removing unsafe products from the market or taking other timely actions to protect consumers. FDA has a number of tools at its disposal to take enforcement actions against dietary supplements found to have safety, labeling, or other violations of the Federal Food, Drug, and Cosmetic Act, as amended by DSHEA. The agency has used a variety of regulatory tools from enforcement actions to rulemaking, when it has found dietary supplements that cause safety concerns (e.g. digitalis-contaminated plantain, Gamma butyrolactone and Gamma hydroxybutyrate). Additionally, the agency has taken action against products marketed as dietary supplements, but which are illegally making claims as to usefulness in the treatment, diagnosis, cure, or prevention of disease (e.g. Pro-Symbio PLUS).
For more information on dietary supplements and a summary of DSHEA, please visit the Center for Food Safety and Applied Nutrition (CFSAN) Web site or contact CFSAN at the following address:
Center for Food Safety and Applied NutritionFDA believes that pharmacists play a major role in the health care delivery system. Pharmacists are accessible to consumers to provide counseling and answer questions regarding the use of medical products. Consumers do ask pharmacists about interactions of foods, the use of over-the-counter medications, or dietary supplement interactions with prescription medications. Also, verbal counseling by pharmacists provides reinforcement of the written information dispensed with the prescription. FDA thinks this important role of pharmacists will help consumers to avoid or reduce adverse events associated with the use of their prescription medications.
FDA considers it very important for patients to receive appropriate risk information as well as instructions for use regarding the products prescribed for them. Pharmacists, together with other health care professionals, can and do provide essential information in educating consumers on safe and effective use of their medical products.
A. Although drugs are required to be safe, safety does not mean zero risk, since all drugs are associated with risks. A safe drug is one that has reasonable risks, given the magnitude of the benefit expected and the alternatives available. However, the true picture of product safety actually evolves over the months and even years that make up a product's lifetime in the marketplace. Because the clinical trials that help gauge product safety are conducted under limited circumstances, problems can remain hidden, only to be revealed after the product is approved. For example, a patient runs the risk of experiencing reactions resulting from the product's interaction with the body, although these usually have been identified and are indicated as possible risks in a product's labeling. Clinical trials may be conducted in relatively small groups of individuals when compared to the hundreds of thousands or even millions of people that use the product, and assessment of effects of every new drug in combination with other approved drugs present additional considerations. It is for these reasons that we require post-marketing surveillance of a product.
Through the MedWatch program, the agency is better able to conduct post-marketing surveillance. It is a voluntary system of reporting to staff at the FDA adverse effects and product problems. Recently, we have made it possible to submit MedWatch reports electronically. You can find a link to the Internet voluntary reporting form by going to the MedWatch home page at www.fda.gov/medwatch/. Select the "How to Report" text, then the "Reporting by Health Professionals" or "Reporting by Consumers" text. Alternatively, you can go directly to the Internet online form. The information obtained from collected reports is entered into our Adverse Event Reporting System (AERS) database. We continuously monitor the AERS system to identify emerging patterns. In the event we observe a potential for a widespread product problem, the agency will initiate action as needed.
Regarding concerns of drug interactions, the Office of Clinical Pharmacology and Biopharmaceutics within the Center for Drug Evaluation and Research (CDER), in addition to already existing programs, has initiated several activities related to drug interactions. These include information technology, guidance development, intramural and extramural research, and quality assurance.
One of Dr. Jane Henney's first initiatives, after being sworn in as the new Commissioner of FDA, was to create a Task Force to evaluate the system for managing risks from medical product use and focusing on FDA's role in the risk management system. Representatives from each of the five FDA centers within the FDA were on the Task Force. This Task Force reviewed the practices of all aspects of the health care delivery system and roles and responsibilities of each participant. The FDA's role was evaluated in-depth from premarketing approval through the postmarketing surveillance system. The Task Force also made conclusions and recommendations and identified options on how FDA can maximize the benefits but minimize the risks associated with medical product use. The report is available in its entirety at the following address: www.fda.gov/oc/tfrm/riskmanagement.html.
A. The two main tools for pediatric drug development are the Pediatric Exclusivity Provisions of the Food and Drug Administration Modernization Act (FDAMA), enacted on November 21, 1997, and the Pediatric Final Rule published in the Federal Register on December 2, 1998. The chart below briefly describes some of the differences between the two documents:
| Modernization | Final Rule |
|---|---|
| Pediatric studies are voluntary | Pediatric studies are required for new drugs
and previously marketed drugs that meet certain criteria |
| To earn exclusivity, studies must be conducted on the active moiety of the drug for all appropriate indications and pediatric age groups | To fulfill the requirements of the rule, a
sponsor must evaluate the need for pediatric information only on the drug
product and indication currently being reviewed or to be submitted. Pediatric
information also may be required for certain drugs already being marketed. |
| Incentive: 6 month marketing exclusivity | May qualify for pediatric exclusivity |
FDA compiled a List of Approved Drugs for Which Additional Pediatric Information May Produce Health Benefits in the Pediatric Population under the pediatric exclusivity provisions of FDAMA. This list is available on the CDER pediatrics page: www.fda.gov/cder/pediatric/, and is updated at least annually in compliance with the statute. FDA notes that inclusion of a drug on the list does not mean that a sponsor is required to undertake pediatric studies.
The second part of FDA's Pediatric Drug Development Plan is the Pediatric Final Rule, which became effective on April 1, 1999. Under the rule, all applications for new active ingredients, new dosage forms, new indications, new routes of administration, and new dosing regimens must contain an assessment of the safety and effectiveness of the product in pediatric patients at the time of approval unless the requirement is waived or deferred. In addition, FDA may require a sponsor to conduct a pediatric assessment for an already-marketed drug, but only if one of the following criteria is met:
FDA estimates that it will require studies of approximately two marketed drugs per year.