The Evolution of FDA's Role in Ensuring Product Quality

The quality of a drug product is an essential element of drug safety and efficacy. With a statutory mission to provide safe and effective medications to the public, the US Food and Drug Administration has always focused on drug quality. The authors summarize the history of FDA's role in ensuring product quality and its role in shaping risk-based approaches to this goal.
Jul 02, 2007
Volume 31, Issue 7

People have always been concerned about the quality of the products they use—especially those products that are consumed or used for medicinal purposes. Regulation of medicinal products began with inspection of imported drugs in 1848 when Congress passed the Drug Importation Act, requiring the US Customs Service to stop entry of adulterated drugs from overseas. The Federal Food and Drugs Act introduced in 1880 and later authorized by Congress in 1906, prohibited misbranded and adulterated foods and drugs in interstate commerce. There were many shortcomings with the Federal Food and Drugs Act such as evaluating the safety and efficacy of drug products, however, and FDA did not have enough regulatory discretion to carry it out; a complete revision was recommended.

Empowering FDA and shaping regulation

Milestone. 30 years of Pharmaceutical Technology
It was not until the sulfanilamide elixir disaster that killed 107 people, many of them children, 31 years later in 1937 that Congress moved toward authorizing a new law. In 1938, President Franklin D. Roosevelt signed the Federal Food, Drug, and Cosmetic Act (FD& C Act), providing the basis to establish safety of pharmaceuticals. The act provided FDA with new enforcement provisions, including extending control to cosmetics and therapeutic devices, and authorized standards for the identity and quality of food and drugs. Although the main focus was to ensure safety of therapeutic products, quality soon became a priority as drug products with compromised quality were often found to be unsafe for human use (1). It is significant to note that the FD&C Act was a consequence of product quality issues involving an excipient in drug safety (diethylene glycol).

FDA's primary goal is to ensure that safe and effective quality medicines are available to the American public. Quality issues, however, arise across myriad groups involved in the process between a drug's creation and its placement on the market, including manufacturers, distributors, and repackagers. With the 1993 launch of a multiple adverse event reporting system (AERS) called MEDWATCH, designed for voluntary reporting of problems with medical products to be filed with FDA by health professionals, it became mandatory for drug manufacturers to report any unexpected and serious adverse events to the agency in a timely manner (2). With the help of the AERS database, the agency recognized several safety issues related to drug product quality. As a result, there were numerous recalls or seizures of drug products by the agency for failure to comply with the quality standards set forth (2).

Depending upon the severity of adverse health consequences, recalls are divided into three classes. Class I is the most serious, sometimes based on death; Class II is based on temporary or medically reversible health consequences; and Class III is based on low likelihood of health consequences. Instead of recalls, market withdrawal can also occur in which the firm removes the product from the market or corrects the violation (3). Numerous voluntary recalls by manufacturers have resulted from failure to produce the drug products according to quality standards. Several times, all the drug products from a manufacturer were recalled because of substandard manufacturing conditions in the firm. (4, 5).

The 1951 Durham-Humphrey Amendment ensured that a prescription drug dispensed without a prescription be treated as a "misbranding" by FDA (6). The thalidomide crisis of 1960–61 in which thousands of babies were born with phecomelia deformities, mostly in Europe because the product was not approved in the United States, led to further amendments for drug effectiveness studies. Several products were grandfathered for effectiveness studies by the sponsor, and FDA was authorized to apply the 1962 Drug Efficacy Study Implementation amendment to those drugs. The amendment to the FD&C Act, called the Kefauver-Harris Amendment, also tightened safety standards (7). Another significant act of the last 30 years was promulgated as the Hatch-Waxman Act (1984) (8). This act allowed companies to market generic versions of approved brand products. As a result, preclinical and clinical studies were waived for many generic products.

A generic product is deemed comparable to the brand product if the dosage form, strength, route of administration, quality and performance characteristics, and intended use are deemed similar. FDA's Orange Book lists all agency-approved products as new drug applications (NDAs), abbreviated new drug applications (used for generics), and nonmonograph over-the-counter products. It also indicates when or whether a product is substitutable for an NDA.

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