“Off label use” is a bit of an odd thing. The FDA does not regulate the practice of medicine, but it does get involved in the labeling of medical devices and pharmaceuticals through the applicable pre-marketing review processes, and those labels identify the use (or uses) intended for that medical product. That use (or those uses) are ones for which there is reasonable evidence of safety and efficacy, in the FDA’s estimation, but the practice of medicine moves faster than the regulatory process. Once an approved device or drug is available, doctors can prescribe it for any purpose they believe is warranted—regardless of what the label says. Indeed, sometimes it is the medical standard of care to prescribe a medical product for uses other than what is stated on the label.
But when a use is off-label, what role can or should a manufacturer have in discussions with physicians or medical debate about those off-label uses? The idea of manufacturers paying for ads that say “use our ProductTM for condition X” when the FDA has only reviewed the clinical data and authorized the ProductTM to be labeled for condition Y makes many uneasy. But what if using Product for condition Y has become the standard of care—can the manufacturer communicate with doctors about that? What if there are quality, published scientific articles about that unapproved use? Can the manufacturer unilaterally send out copies? Can the manufacturer provide copies of that quality, published scientific article, but only if a physician asks for it?
The FDA has—shall we say—fluctuated over time about what is, or is not, permissible for a manufacturer to say or do with respect to off-label uses (or, in its parlance, “unapproved uses”). There was an earlier final guidance issued in 2009, “Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices.”
That was replaced in 2014 with a draft guidance “Distributing Scientific and Medical Publications on Unapproved New Uses–Recommended Practices.”
That March 2014 draft guidance was replaced by a revised draft guidance in October 2023 (“2023 Draft Guidance”).
And now, on Monday, January 6, 2025, the FDA issued its new final guidance, “Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products: Questions and Answers” (“2025 Final Guidance”) to describe its
enforcement policy regarding certain firm-initiated communications of scientific information on unapproved use(s) of the firm’s approved/cleared medical products to health care providers (HCPs) engaged in prescribing or administering medical products to individual patients.
The Federal Register notice is here.
Overall, the framework of the 2025 Final Guidance will be familiar. It describes certain types of manufacturer-initiated communications with health care providers about off-label uses that should not result in enforcement action by the FDA, which clearly suggests that other types of communications about off-label uses (even if truthful and not misleading) are potentially fair game for FDA enforcement.
In particular, the 2025 Final Rule attempts to articulate how a manufacturer of an approved/cleared medical product can stay out of regulatory trouble by providing a Q&A series about what to do, or not to do. For example, any manufacturer-initiated communications to physicians about off-label uses should be “scientifically sound” and of a certain type (published scientific or medical journal articles, clinical practice guidelines, reference texts, or digital clinical practice resources). They also must be accompanied by the current approved labeling, additional statements (about the approved use, that the unapproved use has not been approved by FDA, and that the safety and effectiveness of the medical product for the unapproved use(s) has not been established); and relevant warnings and contraindications; and so on.
There are, of course, First Amendment questions raised by any attempts to regulate speech about off-label use, and those questions remain present with the 2025 Final Guidance as well. If the manufacturer’s speech about the use of ProductTM for Condition Y is not false or misleading in any respect, can a regulation restricting that speech be consistent with the First Amendment? That is a topic near-and-dear to the heart of Bexis, as covered in numerous posts.
The 2025 Final Guidance does acknowledge, at least to some degree, that there are First Amendment implications raised by a regulatory guidance directed at speech. But there is nothing really new from the Agency on the First Amendment issue in the 2025 Final Guidance. Mostly, the 2025 Final Guidance cites the FDA’s own January 2017 Memorandum, “Public Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products” which was pretty well picked apart in this post.
More recently, Bexis has suggested that Loper Bright provides a pathway for courts to independently examine the statutory and regulatory framework (house of cards?) that the FDA traditionally has used to justify enforcement of its policies about off-label promotion, and decide for themselves whether they provide the authority the FDA says it has. The 2025 Final Guidance takes a stab at articulating the relevant “FDA Authorities” that empower its oversight of information about off-label uses, but it is no more compelling than the Agency’s earlier justification attempts. Compare 2025 Final Guidance at 7 & fn. 13-16 with 2023 Draft Guidance at 2 & fn. 3.
Bexis also has posited that the FDA exceeds its authority in attempting to regulate information about off-label uses, and thus is vulnerable to a legal challenge to its regulatory guidances, in Is the FDA’s Off-Label Speech Proposal Infected with the Ultra Vires? Nothing in the 2025 Final Guidance seems to address or anticipate Loper Bright-based challenges, however.
Off label will never be off topic on this blog, so undoubtedly there will be more to come as we ruminate some more now that the 2025 Final Guidance finally is here.