"Off-label promotion"—that is, the promotion of a product for a use other than one for which FDA has granted approval—has been an issue that has bedeviled both industry and FDA. The pharmaceutical industry has paid literally billions of dollars in False Claims Act settlements for off-label promotion, but in recent years, FDA has been on the losing end of cases challenging its regulation of truthful, non-misleading off-label statements on First Amendment grounds. FDA's struggle to bring at least some order to this quagmire has now been delayed.
On Friday, March 17, FDA delayed for a whole year the effective date of a final rule amending its "intended use" regulation. The concept of "intended use" is fundamental to FDA's regulatory regime. For example, a product's intended use determines whether it statutorily qualifies as a drug, device, or other regulated product under the Food, Drug, and Cosmetic Act (FDCA) and, thus, is regulated by FDA. The concept also undergirds claims of off-label promotion. Drugs, for example, are approved for specific uses that must be described in the drug's label. If evidence shows that a pharmaceutical representative is promoting a product for an unapproved use, those statements can be evidence of a manufacturer's intended use of the drug, and the manufacturer can be punished for misbranding the product (essentially, not labeling the drug correctly).
In 2015, FDA proposed a change to its intended use regulation that some believed eliminated a long-standing concern that a manufacturer's mere knowledge of an off-label use could be used as evidence of a product's intended use. In the final rule issued in 2017, FDA amended the proposed regulation to put in place a "totality of the evidence" standard, under which FDA may consider direct and circumstantial evidence to establish a product's intended use. FDA has explained that its proposed rule was meant to clarify that "mere knowledge" of an off-label use is insufficient to establish a product's intended use, but that intended use can, in fact, be based on "any relevant source of information." Thus, FDA issued the final rule with a "totality of the evidence" standard expressly included in the regulation's text.
FDA delayed the effective date of the final rule after industry groups filed a citizen petition arguing that FDA's final rule violated the Administrative Procedure Act and promulgated a “new and unjustified” "totality of the evidence" standard. With regard to the latter concern, the petitioners argued that the proposed rule appropriately eliminated a knowledge standard and limited the query of intended use to a manufacturer's promotional statements (e.g., labeling, advertisements, and sales and marketing activities), but the final rule, unmoored to the FDCA and case law, allowed consideration of any evidence, including a manufacturer's knowledge.
In its notice delaying the effective date of the final rule, FDA seeks comments on the proper interpretation of intended use. In particular, FDA is interested in the public's comments on whether it is appropriate to limit the intended use inquiry to a manufacturer's promotional statements and whether that limitation has public health implications. FDA appears to be motivated by a concern that manufacturers will be able to skirt regulations by not making promotional claims, or at least not doing so explicitly, even despite factors such as the known effects of a product or substance.
Given the importance of intended use, manufacturers are encouraged to submit comments on FDA's proposed change to the regulation. The "totality of the evidence" concept is subject to interpretation, and we suggest that you seek guidance from your counsel on how best to address this issue internally.