A Drug Review Glossary

Abbreviated New Drug Application, or ANDA: A simplified submission permitted for a duplicate of an already approved drug. ANDAs are for products with the same or very closely related active ingredients, dosage form, strength, administration route, use, and labeling as a product that has already been shown to be safe and effective. An ANDA includes all the information on chemistry and manufacturing controls found in a new drug application (NDA), but does not have to include data from studies in animals and humans. It must, however, contain evidence that the duplicate drug is bioequivalent (see "Bioequivalence") to the previously approved drug.

Accelerated Approval: A highly specialized mechanism intended to speed approval of drugs promising significant benefit over existing therapy for serious or life-threatening illnesses. It incorporates elements aimed at making sure that rapid review and approval is balanced by safeguards to protect both the public health and the integrity of the regulatory process. This mechanism may be used when approval can be reliably based on evidence of a drug's effect on a "surrogate endpoint" (see "Surrogate Endpoint"), or when FDA determines an effective drug can be used safely only under restricted distribution or use. Usually, such a surrogate can be assessed much sooner than such an endpoint as survival. In accelerated approval, FDA approves the drug on condition that the sponsor study the actual clinical benefit of the drug.

Action Letter: An official communication from FDA to an NDA sponsor that informs of a decision by the agency. An approval letter allows commercial marketing of the product. An approvable letter lists minor issues to be resolved before approval can be given. A not approvable letter describes important deficiencies that preclude approval unless corrected.

Advisory Committee: A panel of outside experts convened periodically to advise FDA on safety and efficacy issues about drugs and other FDA-regulated products. FDA isn't bound to take committee recommendations, but usually does.

Amendment to an NDA: A submission to change or add information to an NDA or supplement not yet approved.

Bioavailability: Rate and extent to which a drug is absorbed or is otherwise available to the treatment site in the body.

Bioequivalence: Scientific basis on which generic and brand-name drugs are compared. To be considered bioequivalent, the bioavailability of two products must not differ significantly when the two products are given in studies at the same dosage under similar conditions. Some drugs, however, are intended to have a different absorption rate. FDA may consider a product bioequivalent to a second product with a different rate of absorption if the difference is noted in the labeling and doesn't affect the drug's safety or effectiveness or change the drug's effects in any medically significant way.

Clinical Studies: Human studies designed to distinguish a drug's effect from other influences--for example, a spontaneous change in disease progression or in the effect of a placebo (an inactive substance that looks like the test drug). Such studies conducted in this country must be under an approved IND (see "Investigational New Drug Application"), under the guidance of an institutional review board, and in accord with FDA rules on human studies and informed consent of participants.

Drug Product: The finished dosage form (tablet, capsule, etc.) that contains a drug substance--generally, but not necessarily, in association with other active or inactive ingredients.

Drug Substance: The active ingredient intended to diagnose, treat, cure, or prevent disease or affect the structure or function of the body, excluding other inactive substances used in the drug product.

Effectiveness: The desired measure of a drug's influence on a disease condition. Effectiveness must be proven by substantial evidence consisting of adequate and well-controlled investigations, including human studies by qualified experts, that prove the drug will have the effect claimed in its labeling.

Investigational New Drug Application, or IND: An application that a drug sponsor must submit to FDA before beginning tests of a new drug on humans. The IND contains the plan for the study and is supposed to give a complete picture of the drug, including its structural formula, animal test results, and manufacturing information.

New Drug: A drug first investigated or proposed for marketing after 1938 (when the Federal Food, Drug, and Cosmetic Act was passed)--that is, the drug was not generally recognized as safe and effective before that date.

New Drug Application, or NDA: An application requesting FDA approval to market a new drug for human use in interstate commerce. The application must contain, among other things, data from specific technical viewpoints for FDA review--including chemistry, pharmacology, medical, biopharmaceutics, statistics, and, for anti-infectives, microbiology.

Parallel Track Mechanism: A U.S. Public Health Service policy that makes promising investigational drugs for AIDS and other HIV-related diseases more widely available under "parallel track" protocols while the controlled clinical trials essential to establish the safety and effectiveness of new drugs are carried out. The system established by this policy is designed to make the drugs more widely available to patients with these illnesses who have no therapeutic alternatives and who cannot participate in the controlled clinical trials.

Pharmacology: The science that deals with the effect of drugs on living organisms.

Post-Marketing Surveillance: FDA's ongoing safety monitoring of marketed drugs.

Preclinical Studies: Studies that test a drug on animals and other nonhuman test systems. They must comply with FDA's good laboratory practices. Data about a drug's activities and effects in animals help establish boundaries for safe use of the drug in subsequent human testing (clinical studies). Also, because animals have a much shorter lifespan than humans, valuable information can be gained about a drug's possible toxic effects over an animal's life cycle and on offspring.

Raw Data: Researcher's records of patients, such as patient charts, hospital records, x-rays, and attending physician's notes. These records may or may not accompany an NDA, but must be kept in the researcher's file. FDA may request their submission or may audit them at the researcher's office.

Safety: No drug is completely safe or without the potential for side effects. Before a drug may be approved for marketing, the law requires the submission of results of tests adequate to show the drug is safe under the conditions of use in the proposed labeling. Thus, "safety" is determined case by case and reflects the drug's risk-vs.-benefit relationship.

Safety Update Reports: Reports that an NDA sponsor must submit to FDA about any new safety information that may affect the use for which the drug will be approved, or draft labeling statements about contraindications, warnings, precautions, and adverse reactions. Safety update reports are required four months after the application is submitted, after the applicant receives an approvable letter, and at other times upon FDA request.

Supplement: A marketing application submitted for changes in a product that already has an approved NDA. FDA must approve all important NDA changes (in packaging or ingredients, for instance) to ensure that the conditions originally set for the product are not adversely affected.

Surrogate Endpoint: A laboratory finding or physical sign that may not, in itself, be a direct measurement of how a patient feels, functions or survives, but nevertheless is considered likely to predict therapeutic benefit. An example would be CD4 cell counts, used to measure the strength of the immune system.

Treatment IND: A mechanism that allows promising investigational drugs to be used in "expanded access" protocols--relatively unrestricted studies in which the intent is both to learn more about the drugs, especially their safety, and to provide treatment for people with immediately life-threatening or otherwise serious diseases for which there is no real alternative. But these expanded access protocols also require researchers to formally investigate the drugs in well-controlled studies and to supply some evidence that the drugs are likely to be helpful. The drugs cannot expose patients to unreasonable risk.

User Fees: Charges to drug firms for certain NDAs, drug products, and manufacturing establishments. FDA uses these fees to hire more application reviewers and to accelerate reviews through the use of computer technology.