On January 18, 2017, two days before President Trump took office, the US Food and Drug Administration (FDA) issued two pieces of draft guidance for off-label communications. The first addresses communications with payors and formulary committees, and the second outlines “Questions and Answers” about how FDA evaluates communications about information not contained in approved labels for medical products.  In an unusual move, FDA simultaneously released an extensive but informal memorandum entitled “Public Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products”, to notify the public about the issues that it is considering as it attempts to overhaul its policies on what manufacturers can say about the off-label uses of their products.  Industry has been seeking guidance from FDA for many years, even more so in light of recent court decisions pushing back on regulation of truthful and non-misleading off-label communications (See U.S. v. Caronia, 703 F.3d 149 (2nd Cir. 2012) and Amarin Pharm, Inc. v. FDA, No. 15 Civ. 35888, 2015 WL 4720039, 2015 U.S. Dist. LEXIS 103944 (S.D.N.Y. Aug. 7, 2015)).

FDA used this memorandum to restate its position that communications promoting an off-label use of drugs or medical devices should generally be prohibited even when those statements are true. The FDA is in the process of reexamining its approach to the issue, and the memorandum articulates its analysis of the competing interests at stake. The primary argument for relaxing restriction considered in the memorandum is that many kinds of off-label promotion, when truthful, are protected by the First Amendment. Having conceded this point, however, FDA then rejected it. Instead, FDA maintained its narrow interpretation of free speech jurisprudence going back to Sorrell v. IMS Health, (564 U.S. 552 (2011)) and Caronia.  Indeed, the memorandum relies heavily on the argument that the First Amendment is not implicated because the regulated activity is the sale of the product, not the speech promoting the sale. Therefore, the factual promotional statements are not being directly regulated but are instead mere evidence of the intent to sell the product for off-label use.  The Second Circuit found this argument unpersuasive in Caronia, and, by continuing to rely on this reasoning after declining to appeal Caronia, FDA sidesteps successful legal challenges to continue banning even truthful, off-label promotion. (For more analysis, see Norton Rose Fulbright analysis of Amarin litigation).

The FDA memorandum also lists and rejects a broad variety of alternative implementation strategies. The memorandum makes clear that the long-running legal and policy debate over the parameters for off-label promotion will continue.  Although the Trump Administration will have its own opportunity to address the issue in the months and years to come, this memorandum may be the FDA’s attempt to defend its old policies and influence new policy in the new Trump administration.

Broadly, FDA argued in the memorandum that the Federal Food, Drug, & Cosmetic Act (FDCA) and the Medical Device Amendments of 1976 (MDA) mandate that drug and device sales be supported by robust scientific evidence of a product’s safety and efficacy when used as intended. Although FDA acknowledged that off-label promotion can provide information relevant to patient care and encourage further research, the memorandum concluded that off-label promotion is incompatible with FDA’s mandate for several reasons:

  • Promotion of medical products based on market acceptance rather than scientific evidence could result in “wide scale public health tragedies”, waste, and fraud.
  • Only premarket review of safety and efficacy protects public health.
  • FDA review of promotional claims protects the public against institutional bias, misrepresentation, and fraud.
  • FDA review ensures that labels are accurate and informative.
  • Regulation of promotional claims protects the integrity and reliability of medical products and the healthcare system.
  • Widespread availability of medical products for off-label use would weaken incentives to conduct clinical trials needed to demonstrate safety and efficacy.

Allowing off-label promotion undermines both FDA’s ability to encourage and protect innovation and the efficacy of statutory grants of exclusivity (e.g. the Hatch-Waxman Amendments and Orphan Drug Program).In the memorandum, the agency cites to certain of its prior guidance documents to demonstrate that some manufacturer communications about off-label use strike an acceptable balance, including, for example, communications supporting third-party research and responses to unsolicited requests for information. (See Revised Draft Guidance for Industry, Distributing Scientific and Medical Publications on Unapproved New Uses–Recommended Practices (Feb. 2014); Good Reprint Practices for Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices, Guidance for Industry (Jan. 2009); Draft Guidance for Industry, Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices (Dec. 2011); Guidance for Industry, Industry-Supported Scientific and Educational Activities (Dec. 1997)).

Significantly, FDA devoted a substantial portion of the memorandum to enumerating and rejecting alternative approaches to its implementation of the FDCA and MDA. These rejected approaches included:

  • Allowing off-label promotion accompanied by disclosure and warnings.
  • Permitting off-label promotion in medical compendia.
  • Capping the number of off-label prescriptions allowed for an unapproved use.
  • Restricting Medicare/Medicaid reimbursement to approved uses.
  • Tiered restrictions on off-label promotion based on level of safety concern.
  • Allowing only demonstrably false or misleading statements to stand as evidence of intentional sale for off-label use.
  • Prohibiting off-label use of medical products all together.
  • Barring approval of generics until all periods of exclusivity expire.
  • Requiring all potential indications to be considered in the pre-market application.
  • Educating patients and physicians on how to identify false and misleading claims.
  • Reminding physicians of potential malpractice liability associated with off-label prescriptions.
  • Increasing taxes on off-label sales.

The agency acknowledged that these approaches do not “take into account the public health interests behind allowing health care providers and patients to work to determine the best treatment options for each patient in specific circumstances.” However, FDA also states that recent studies have found that most unapproved uses for which drugs are prescribed lack adequate evidence of effectiveness, and that the risk of adverse events is higher for unapproved versus approved uses and even higher when the unapproved use is not supported by reliable scientific data.  Many of these alternative approaches were discussed at a public hearing held on November 9-10, 2016. In the memorandum, FDA invites comments and further dialogue as its evaluation of the issue continues.  FDA also announced on January 19, 2017 that it is reopening the comment period so that stakeholders may provide their insights and concerns; the comment period is now open until April 19, 2017 and stakeholders concerned about FDA’s position should use this opportunity to be heard.

Once President Trump has appointed a new FDA Commissioner, we will learn more about the agency’s objectives, including its take on the free speech vs. off-label promotion debate. We will continue to monitor FDA’s position and will post updates accordingly.