There are more than 250,000 over-the-counter (OTC) products on the market today with wide access to consumers. But after a series of major OTC drug recalls, regulators and standardsetting bodies seem to be taking a closer look at these readily available products.
OTC approvals: a brief historyBefore the 1960s and 1970s, OTC drug sponsors were not required to demonstrate drug effectiveness. But in 1962, FDA required manufacturers to show effectiveness, and in 1972, the agency began what's known as the OTC Monograph System (also called the OTC Drug Review process), a project that is still underway today. The project involved reviewing in great detail the hundreds of compounds available to consumers in OTC form and developing FDA monograph requirements for drugs to be considered as generally recognized as safe and effective (GRAS/E).
All drugs, including OTCs, for human use in the US market must: adhere to current compendial standards; meet labeling requirements called for in the Code of Federal Regulations (CFR) and in the Federal Food, Drug, and Cosmetic Act; and be manufactured according to cGMPs, which are outlined in 21 CFR Parts 210, 211, and 330 (2). GMP compliance is verified through FDA inspections. Any OTC drug that deviates from a final monograph is not recognized as GRAS/E and requires an approved application (i.e., a new drug or abbreviated new drug application, NDA or ANDA) before it can be marketed (3). OTC drugs that meet final monograph requirements do not require an application approval.
Compendial drug quality monographs, or written standards, are published and maintained for the US marketplace by the US Pharmacopeial Convention (USP) and published in the USP–NF. FDA monographs, which are for conditions for market entry, are published in the CFR. An OTC drug monograph includes requirements for the active ingredient's dosage strength and form as well as for the product's labeling and final formulation testing (1).
As part of the OTC Drug Review process, FDA ended up restricting in the 1970s the use of some 500 active ingredients that had previously been on the market because of a lack of sufficient demonstration of effectiveness or lack of general recognition of safety. To date, the agency has completed a review of more than three-fourths of the original monographs proposed at the inception of the program, according to FDA spokesperson Lisa Kubaska. Certain OTC medicines can be reviewed again when a monograph is amended or when a new question of safety or efficacy is raised.
Despite the differences in OTC monograph-drug reviews, NDAs and ANDAs for nonprescription products are examined in the same manner as prescription products. According to FDA, there are 774 OTC products on the market today that were approved by NDA or ANDA.
Another mechanism by which a drug can enter the market as an OTC drug is to undergo a status switch from a prescription drug to a nonprescription drug. The labeling process for this type of switch is quite complex and described later in this article.