Appendix B
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.
Action Letter:
An official communication from the FDA to an NDA sponsor that informs it 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 (see "Conditional Approval"). A not approvable letter describes important deficiencies that preclude approval unless corrected.
Advisory Committee:
A panel of outside experts convened periodically to advise the FDA on safety and efficacy issues about drugs and other FDA-regulated products. The FDA is not bound to follow committee recommendations, but its decisions usually parallel the recommendations of its advisory committees.
Amendment to an NDA:
Submitted to change or add information to a not yet approved NDA or a supplement.
Approval:
The FDA approves the application without conditions, or if the company agrees to the specified conditions, and the company may begin to market the technology upon receipt of the order.
Bench Testing:
Testing of a device against specifications in a simulated environment that does not include the living body of a human or animal. Also known as in vitro device readiness testing.
Bioavailability:
The rate and extent to which a drug is absorbed or is otherwise available to the treatment site in the body.
Bioequivalence:
The 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. The 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 does not affect the drug's safety or effectiveness or change the drug's effects in any medically significant way.
Class I:
An FDA classification of devices for which the general controls of the Food, Drug, and Cosmetic Act are sufficient to provide a reasonable assurance of safety and effectiveness. Approximately 30 percent of devices are in Class I.
Class II:
Devices for which Class I controls alone are not sufficient but for which these controls plus special requirements win provide reasonable assurance of safety and effectiveness. Approximately 60 percent of devices are in Class II.
Class III:
A premarket approval class for devices that cannot be placed in either Class I or Class II. A device in this class has at least one of the following characteristics: it is purported for use in supporting or sustaining human life or for a use that is of substantial importance in preventing the impairment of human health; it presents a potentially unreasonable risk of illness or injury; or it is a transitional device. Approximately 10 percent of devices are in Class III.
Clinical Studies:
Clinical, or human, studies aim 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, in accord with FDA rules on human studies, and with the informed consent of participants.
CNDA:
Computerized NDA; see "NDA."
Conditional Approval:
The FDA sends an approvable letter (see "Action Letter" and "Approval"), citing specific conditions to which the company is asked to agree. This means that the FDA believes there is reasonable assurance of safety and effectiveness, but that certain conditions must be imposed on the company.
Diffusion:
The process by which use of a technological innovation in a given social system spreads over a period of time. (See "Technological Innovation.")
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:
In health care policy and clinical care, "effectiveness" usually refers to the performance and evaluation of a health care technology in general clinical use. "Efficacy," by contrast, is used to denote the use and evaluation of a health care technology under highly controlled conditions by unusually qualified practitioners. Unfortunately, in various pieces of legislation pertaining to the FDA, effectiveness is used to refer to the controlled, highly evaluative use usually associated with the evaluation of efficacy. Because the definitions of effectiveness that are set out in law are contrary to the usual meaning of the word, when used by the FDA "effectiveness" often refers to what can more precisely—or consistently—be called efficacy.
Efficacy:
See "Effectiveness."
Enforcement:
Before a product is marketed, enforcement is the monitoring of clinical investigators and product sponsors. Once a product is on the market, enforcement also includes the inspection of products and manufacturers.
Investigational New Drug Application, or IND:
An application that a drug sponsor must submit to the 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.
In vitro bench testing:
See "Bench Testing."
In vivo testing:
Testing in the living body of a plant or animal.
New Drug:
A drug first investigated or proposed for marketing after 1938, when the Federal Food, Drug, and Cosmetic Act was passed. This means that 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 clinical studies needed for FDA review from specific technical viewpoints, including chemistry, pharmacology, medical, biopharmaceutics, statistics, and—foranti-infectives—microbiology.
Pharmacology:
The science that deals with the effect of drugs on living organisms.
Post-Marketing Surveillance:
FDA's ongoing safety monitoring of marketed drugs.
Pre-Clinical Studies:
Studies that test a drug on animals and other nonhuman test systems. They must comply with the 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 life span than humans, valuable information can be gained about a drug's possible toxic effects over an animal's life-cycle and on offspring.
Pre-Market Approval:
The device manufacturer must provide reasonable assurance of safety and effectiveness under the conditions of intended use. Under the 1976 Medical Device Amendments, the FDA had to submit all pre-marketing approval applications to an advisory committee for a recommendation on the decision. The Safe Medical Devices Act of 1990, however, allows the FDA discretion in deciding which applications to submit to an advisory committee.
Pre-Market Notification (510 (k)):
The manufacturer presents evidence that its device is substantially equivalent to an earlier, approved device. Approximately 5,000 to 6,000 510(k)s are received in a year, and about 90 percent of devices thus submitted are judged to be substantially equivalent. If the device is not substantially equivalent, it is placed in Class III (which requires pre-market approval) and cannot be marketed until a pre-market
Prevalence:
The number of persons in a population that are affected with a particular disease at a given time.
Raw Data:
Researcher's records of patients, such as patient charts, hospital records, X-rays, and attending physician's notes. They may or may not accompany an NDA, but must be kept in the researcher's file. The FDA may request their submission.
Review Clock:
The time frame of 180 days allowed the FDA to review NDAs. The "clock" starts on the date the NDA is received and stops on the date a final action (see "Action Letter" entry) is taken. The FDA may extend the time if significant changes are made to a pending NDA. From the time an NDA is submitted to when it is approved usually is more that 180 days, for any number of reasons—notably, time-consuming amendments to the NDA or a shortage of trained FDA reviewers.
Safety Update Reports:
Reports that an NDA sponsor must submit to the FDA about any new safety information that may affect the 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 the FDA's request.
Supplement:
A marketing application submitted for changes in a product that already has an approved NDA The FDA must approve all important NDA changes (in packaging or ingredients, for instance) to ensure the conditions originally set for the product are not adversely affected.
Surveillance:
The monitoring of adverse reactions and product defects in drugs, biologics, devices, and foods.
Technological innovation:
The process of creating, inventing, or adapting a technology which for a given sector of society, organization, or user. A technology can be a drug, device, clinical procedure, clinical system (e.g, hospital or intensive care unit).
