U.S. Drug Approval Process: A Primer

Publication Date: June 2001

Publisher: Library of Congress. Congressional Research Service

Author(s):

Research Area: Manufacturing and industry

Type:

Abstract:

Drug approval standards in the United States are considered by many to be the most demanding in the world. By law, all new drugs must first be shown to be safe and effective before they can be approved by the Food and Drug Administration (FDA) for marketing. While these requirements are considered the norm today, it took a century of law and rulemaking before they became the nation's gold standard. Up until the early part of the last century, the sale of adulterated and misbranded drugs was not uncommon until the practice was outlawed under the 1906 Food and Drugs Act. Thirty years later, Congress passed the Federal Food, Drug, and Cosmetic Act of 1938, that required drug companies to conduct pre-market safety testing before their new drug could be marketed. In 1962, following the infamous thalidomide tragedy, Congress amended the law once again, this time adding the requirement that manufacturers prove the effectiveness of their products, as well.

Discovering a new drug, and shepherding it through FDA's review process, can take many years, and cost hundreds of millions of dollars. To a large degree, these costs are mostly associated with the clinical testing that must be done to convince the agency that the new product is safe and effective for its intended medical use. To begin clinical testing, drug companies or sponsors must file an Investigational New Drug (IND) application with the FDA. The INDs must include information about the study protocol, the qualifications of the lead investigator, the trial's location, and assurances that the welfare of the study participants will be protected.

Once a new drug's clinical testing is complete, the sponsor submits a New Drug Application (NDA) for FDA evaluation. During the application's review, agency officials examine the drug's safety and efficacy data, assay samples, and conduct factory inspections to be sure the finished product will be manufactured properly. FDA also checks the drug's labeling to be sure that it is accurate and comprehensive. Typically, when FDA finishes its review, it notifies the applicant by letter stating that its NDA is either approved, would be approved if changes are made, or cannot be approved due to unresolved problems. Once a new drug is approved, its safety is monitored through FDA's post-marketing surveillance system, MedWatch. By regulation, manufacturers must report all serious adverse reactions. However, for health professionals and consumers, reporting adverse reactions is voluntary.

During the 1990s, Congress adopted several measures aimed at accelerating the drug approval system. In 1992, it passed the Prescription Drug User Fee Act, which authorized FDA to collect fees from companies in order to speed up NDA review. Five years later, Congress enacted the Food and Drug Administration Modernization Act of 1997 (FDAMA), the most comprehensive overhaul of the nation's food, drug, and medical device laws in more than 30 years. Among its provisions related to the drug approval process, FDAMA streamlined clinical testing requirements, expanded patients' access to experimental drugs, and granted pharmaceutical companies extra marketing exclusivity for determining the use of their products in pediatric patients. FDAMA also eased data reporting requirements, and modified the law so fewer clinical studies are required to confirm a drug's effectiveness.