T he Food and Drug Administration (FDA) oversees the approval and regulation of drugs entering the U.S. market. The agency, part of the Department of Health and Human Services (HHS), is led by the Commissioner of Food and Drugs, who executes the agency's responsibilities on behalf of the HHS Secretary. First, FDA reviews the safety and effectiveness of new drugs that manufacturers wish to market in the United States; this process is called premarket approval or preapproval review . Legislative History of Drug Regulation

The regulation of drugs by the federal government began with the Pure Food and Drug Act of 1906, which prohibited the interstate commerce of adulterated and misbranded drugs. To get that approval, the manufacturer must demonstrate the drug's safety and effectiveness according to criteria specified in law and agency regulations, ensure that its manufacturing plant passes FDA inspection, and obtain FDA approval for the drug's labeling—a term that covers all written material about the drug, including, for example, packaging, prescribing information for physicians, and patient brochures. The drug development process begins before the law requires FDA involvement. Before testing in humans—called clinical testing —the drug's sponsor (usually its manufacturer) must file an investigational new drug (IND) application with FDA. Unless FDA objects, a manufacturer may then begin clinical testing. New Drug Application (NDA)

Once a manufacturer completes clinical trials, it submits a new drug application (NDA) to FDA's Center for Drug Evaluation and Research (CDER). The FFDCA requires "substantial evidence" of drug safety and effectiveness. Supplemental NDA. Regarding clinical data, the applicant must submit descriptions and analysis of controlled and uncontrolled clinical studies, as well as "a description and analysis of any other data or information relevant to an evaluation of the safety and effectiveness of the drug product obtained or otherwise received by the applicant from any source, foreign or domestic, including information derived from clinical investigations, including controlled and uncontrolled studies of uses of the drug other than those proposed in the application, commercial marketing experience, reports in the scientific literature, and unpublished scientific papers." For drugs that address unmet needs or serious conditions, have potential to offer better outcomes or fewer side effects, or meet other criteria associated with improved public health, FDA uses several formal mechanisms to expedite the development or review processes
Fast track and breakthrough product designations affect the administrative processes for the development of a drug and review of an application, for example, by providing for more frequent drug development-related meetings and interactions between the sponsor and FDA. Accelerated approval and animal efficacy approval change what is needed in an application. How FDA Regulates Approved Drugs

FDA's role in making sure a drug is safe and effective continues after the drug is approved and it appears on the market. FDA Drug-Regulation Activities

FDA postmarket drug safety and effectiveness activities address aspects of drug production, distribution, and use. This section highlights nine activities that have traditionally interested Congress in relation to drug safety and effectiveness: product integrity, labeling, reporting, surveillance, drug studies, risk management, information dissemination, off-label use, and direct-to-consumer advertising. Protecting the supply chain from counterfeit, diverted, subpotent, substandard, adulterated, misbranded, or expired drugs remains an essential concern of the agency. Health professionals and patients may report adverse events to FDA's reporting system at any time. Two sets of situations—distinguished by when the requirement is set—involve required postapproval studies: when a requirement is attached to the initial approval of the drug and when FDA informs the sponsor of a required study once a drug is on the market. Animal Efficacy. Based on New Information Available to Secretary. The Secretary, under specified conditions after a drug is on the market, may require a study or a clinical trial. Risk Management

With authority under the FFDCA or by its own practices, FDA has long implemented various tools in its attempt to ensure that the drugs it has approved for marketing in the United States are safe and effective for their intended and approved uses. Elements to assure safe use (ETASU). Among other things, the draft guidance provides examples of the kinds of information that the agency considers consistent with FDA-required labeling for a product (e.g., information that provides additional context about adverse reactions associated with a drug's approved use[s] as reflected in the FDA-required labeling), as well as the kinds of information that are not consistent with FDA-required labeling for a product (e.g., if a drug is approved for treatment of only one disease, and the company's communication provides information about using the product to treat a different disease). This guidance has not been finalized.
The Food and Drug Administration (FDA), a regulatory agency within the Department of Health and Human Services, regulates the safety and effectiveness of drugs sold in the United States. FDA divides that responsibility into two phases. In the preapproval (premarket) phase, FDA reviews manufacturers' applications to market drugs in the United States; a drug may not be sold unless it has FDA approval. Once a drug is on the market, FDA continues its oversight of drug safety and effectiveness. That postapproval (postmarket) phase lasts as long as the drug is on the market. Beginning with the Food and Drugs Act of 1906, Congress and the President have incrementally refined and expanded FDA's responsibilities regarding drug approval and regulation.
The progression to drug approval begins before FDA involvement. First, basic scientists work in the laboratory and with animals; second, a drug or biotechnology company develops a prototype drug. That company must seek and receive FDA approval, by way of an investigational new drug (IND) application, to test the product with human subjects. It carries out those tests, called clinical trials, sequentially in Phase I, II, and III studies, which involve increasing numbers of subjects. The manufacturer then compiles the resulting data and analysis in a new drug application (NDA).
At that point, FDA reviews the NDA with three major concerns: (1) safety and effectiveness in the drug's proposed use; (2) appropriateness of the proposed labeling; and (3) adequacy of manufacturing methods to assure the drug's identity, strength, quality, and purity. The Federal Food, Drug, and Cosmetic Act (FFDCA) and associated regulations detail the requirements for each step. FDA uses a few special mechanisms to expedite drug development and the review process when a drug might address an unmet need or a serious disease or condition. Those mechanisms include accelerated approval, animal efficacy approval, fast track designation, breakthrough therapy designation, and priority review.
Once FDA has approved an NDA, the drug may enter the U.S. market, but FDA continues to address drug production, distribution, and use. Its activities, based on ensuring drug safety and effectiveness, address product integrity, labeling, reporting of research and adverse events, surveillance, drug studies, risk management, information dissemination, off-label use, and direct-to-consumer advertising, all topics in which Congress has traditionally been interested.
FDA seeks to ensure product integrity through product and facility registration; inspections; chain-of-custody documentation; and technologies to protect against counterfeit, diverted, subpotent, adulterated, misbranded, and expired drugs. FDA's approval of an NDA includes the drug's labeling; the agency may require changes once a drug is on the market based on new information. It also prohibits manufacturer promotion of uses that are not specified in the labeling. The FFDCA requires that manufacturers report to FDA adverse events related to its drugs; clinicians and other members of the public may report adverse events to FDA. The agency's surveillance of drug-related problems, which had primarily focused on analyses of various adverse-event databases, is now expanding to more active uses of evolving computer technology and links to other public and private information sources.
The FFDCA allows FDA to require a manufacturer to conduct postapproval studies of drugs. The law specifies when FDA must attach that requirement to the NDA approval and when FDA may issue the requirement after a drug is on the market. To manage exceptional risks of drugs, FDA may also require patient or clinician guides and restrictions on distribution. The agency publicly disseminates information about drug safety and effectiveness; and regulates the industry promotion of products to clinicians and the public.