FDA’s Authority to Regulate Off-Label Promotion

Last year alone, doctors filled out over four billion drug prescriptions in the United States. But according to some estimates, Americans used nearly one-fifth of these prescriptions for uses unauthorized by the U.S. Food and Drug Administration (FDA)—uses that ultimately come with a much greater risk of harm.

Although unauthorized, or “off-label,” uses are frequent and can lead to adverse outcomes, federal law does not explicitly permit FDA to regulate manufacturers’ promotion of off-label uses of drugs. These uses are off-label because the manufactures have not sought FDA approval for the specific uses, often because the safety and effectiveness of these uses lack scientific support. In a recent paper, however, Nathan Cortez, a professor at Southern Methodist University’s Dedman School of Law, argues that federal law does in fact give FDA authority to implement a “functional” ban on the promotion of off-label uses of their drugs.

Cortez notes that two powers given to FDA are key to the enforcement of this functional ban. According to Cortez, these powers, though not specifically directed toward the regulation of off-label promotion, allow the agency to regulate it in practice. The Federal Food, Drug, and Cosmetic Act (FDCA), which provides the overarching framework for pharmaceutical regulation in the United States, does not explicitly prohibit off-label promotion, but it permits FDA to regulate manufacturers’ marketing and branding of drugs and prohibit the introduction of new, unapproved drugs into the market.

FDA has been using its authority to regulate marketing and branding in conjunction with the prohibition on unapproved drugs to create what Cortez calls a “squeeze play” to regulate off-label promotion. Outlining how the squeeze play functions, he explains that a manufacturer engaging in off-label promotion violates misbranding regulations by failing to provide adequate information about uses of the drugs. However, if that manufacturer updates its labeling to remedy that misbranding violation, the manufacturer violates the new drug prohibition by mentioning an unapproved use on the label.

Thus, the squeeze play: A manufacturer engaging in off-label promotion cannot remedy its marketing violation without, in turn, violating the new drug provision.

Cortez further observes that the language of the FDCA, which specifically states that it would “not change any existing prohibitions on the promotion of unapproved uses,” demonstrates that Congress recognized an already existing prohibition on this type of promotion at the time of the Act’s passage. The law’s construction consequently negated the need for an explicit prohibition on the promotion of unapproved uses, which explains the prohibition’s absence.

The text of the statute also creates an expedited procedure for FDA to authorize off-label uses in emergencies, Cortez notes. In part, this procedure allows limited advertising of the off-label use after FDA recognizes an emergency but before FDA authorizes the new use. Cortez argues that by allowing such advertisement in emergency situations, the FDCA assumes that advertisement of off-label uses in non-emergency situations is prohibited.

In addition to examining the FDCA’s text, Cortez pays special attention to the FDCA’s “new drug” provisions, which require manufacturers to submit “substantial evidence” that the drug is safe and effective enough to earn FDA approval. Cortez suggests that FDA’s lacking the authority to regulate off-label promotion would undermine the need for manufacturers to file supplemental applications seeking FDA approval for off-label uses. He explains that without the ability to regulate off-label promotion, drug manufacturers could simply acquire approval for just one use before the drug goes to market.

The FDCA requires substantial evidence to approve a new drug, but most off-label uses lack the substantial evidence necessary for FDA approval. If a manufacturer could promote off-label uses without a supplemental application, Cortez purports that the manufacturer would not take on the expense of a supplemental application. FDA would subsequently not be able to guarantee that there was substantial evidence that every drug on the market was safe and effective.

Relatedly, Cortez argues that an interpretation of the FDCA which does not allow FDA to regulate off-label promotion would “create absurd results.” Cortez contends that if FDA allows off-label promotion, manufacturers will seek FDA approval for only the “narrowest and least controversial uses” of each drug. Manufacturers would have no incentive to file supplemental applications for other, more controversial uses of a drug once it receives narrow approval. Companies could then flood the markets with potentially unsubstantiated claims about off-label uses of drugs that have only the “narrowest” of FDA approvals. Cortez holds that FDA’s drug approval process is one of its most important functions, and allowing companies to skirt the process could not be in line with the intent of the FDCA.

Finally, Cortez looks to Congress’s response to FDA’s regulation of off-label promotion. FDA has been using its “squeeze play” to regulate off-label promotion for years. Congress has amended the FDCA over 100 times since its passage in 1938, but it has not amended the FDCA to clarify away FDA’s assumed authority to regulate off-label promotion. Congress seems to approve of—or at least have acquiesced to—FDA regulation of off-label promotion.

This paper was published in the online supplement to the University of Chicago Law Review.