On August 2, 2021, the Food and Drug Administration (FDA) published its final intended use rule (the “Final Rule”). The Final Rule amends FDA’s regulations describing the types of evidence relevant to determining a product’s intended use under the Federal Food, Drug, and Cosmetics Act (“FDCA”). In addition to playing a key role in defining certain FDA-regulated products, a product’s “intended use” is a pivotal determination for the FDA when enforcing off-label promotion violations under the FDCA’s misbranding and unapproved new drug provisions. Generally, the intended uses of medical products must align with the FDA-approved, licensed, or cleared uses of those same products.
Medical product firms’ promotional materials or statements that create new intended use(s) for their FDA-approved, licensed, or cleared medical product (in the absence of FDA approval, licensure, or clearance for such use(s)) have subjected firms to government enforcement. Off-label promotion violations also carry immense exposure under the False Claims Act (FCA), triggering treble damages and civil penalties. Promoting a medical product for off-label uses can establish liability under the FCA under the theory that a manufacturer caused the federal government to be billed for uses of the product that are not medically accepted.
Unsurprisingly, the pharmaceutical industry has strongly advocated for a more narrow scope of evidence that FDA could use to prove a new intended use. Due at least in part to the industry’s efforts, FDA delayed finalizing this rule for over six years. The initial iteration was proposed in 2015, finalized in 2017, only to be stayed indefinitely in 2018 due to petitions from the industry. After proposing the new rule in September 2020, the FDA has finalized a relatively expansive interpretation of intended use despite some concerns raised by the industry.
The Final Rule provides examples of the types of evidence that are relevant to establishing a medical product’s intended use. The enumerated (but not exhaustive) categories include: (1) express claims and representations; (2) implied claims; (3) product characteristics and design; and (4) circumstances surrounding the sale or distribution of the product. The rule also explains that certain evidence, when standing alone, does not provide sufficient evidence of a new intended use. For example, a manufacturer’s mere knowledge that its drug is being used outside its labeled indications does not establish a new intended use. Nor does providing safety information to providers about an unapproved use. While there are certain actions that standing alone are not dispositive to create liability, the Final Rule was clear that it does not create a blanket “safe harbor” for all forms of scientific exchange of information. Rather, the Final Rule kept intact FDA’s previously recognized safe harbors, including “those that encompass various types of scientific exchange,” but abstained from resolving separate questions relating to scientific exchange, which could be the subject of future rulemaking.
Below are just some of the key comment points that FDA addressed when it finalized the rule.
Any Relevant Source
First, the Final Rule reiterates FDA’s position that “any relevant source” can be considered when determining if a drug is being marketed for a new intended use. It remains to be seen how different this standard is from the “totality of evidence” standard that FDA proposed in its 2017 version of the rule and later abandoned. The “any relevant source” standard was introduced against arguments from industry that evidence should be limited to “promotional claims.” The FDA summarily rejected industry’s approach, insinuating it was far too easy for manufactures to “mask” their true intent in promotional language.
Design or Composition
Another highlight of the Final Rule is that FDA refused to back down from its position that the design or composition of a product can be used as evidence that the manufacturer intended to market the product for an unapproved use. Industry argued that this interpretation is contrary to the statute, however the FDA cited several enforcement actions and claimed it was part of the “longstanding and current” policy.
First Amendment Arguments
Some commenters objected that the rule prohibits truthful non-misleading speech in violation of the First Amendment. There is current legal uncertainty as to the scope of FDA’s authority to criminalize truthful speech; however, FDA maintains that the rule does not unlawfully implicate the First Amendment. FDA contends that the Final Rule uses speech only as evidence of intended use, and cites a litany of case law to support its position that the government may rely on speech as evidence of a medical product’s new intended use under the FDCA.
The Final Rule ultimately codified much of FDA’s existing policies and enforcement practices surrounding off-label promotion, but the intersection of the Final Rule with the First Amendment will likely be the subject of further litigation. Nevertheless, the Final Rule provides additional guidance that can help manufacturers shape their off-label communication compliance practices.
 Final Rule, “Regulations Regarding ‘Intended Uses,’” 86 Fed. Reg. 41383 (Aug. 2, 2021).