The regulatory landscape regarding off-label drug promotion may be changing in light of the Second Circuit’s recent decision in United States v. Caronia.  The opinion of the court concerned the government’s prosecution of off-label drug promotion and held that the Food, Drug, and Cosmetic Act (FDCA) is limited in its ability to restrict off-label speech.  The opinion also questioned in dicta whether the FDCA could in fact be utilized to prosecute a misbranding claim based on truthful, off-label promotion.

A.   Summary of Case

In Caronia, a sales representative and company speaker were recorded promoting off-label uses, including unapproved uses and unapproved subpopulations for approved uses, to a government cooperator.  The court in Caronia noted that the FDCA does not expressly prohibit off-label promotion; rather, the FDCA provides that a drug is misbranded when its labeling fails to provide adequate directions for use or is false or misleading. The lower court found that the prosecution was not based on this type of misbranding, as the government contended, but rather the off-label speech itself.  Nevertheless, the lower court held that the FDCA’s authorities were constitutional and narrowly tailored to the government’s objectives.  The Second Circuit took issue with this prosecution of speech.

The Second Circuit in Caronia, as well as the government prosecution,stated that off-label promotion is only evidence of trying to expand a drug’s intended use and is not, by itself, prohibited under the FDCA.  Rather, the prohibition rests on the failure to provide adequate directions for the off-label use, which renders the drug misbranded.  However, in this case, the Second Circuit observed from the lower court record that the government was actually prosecuting Caronia’s speech itself, rather than using that speech as evidence of an intent to misbrand the drug under the FDCA’s misbranding provisions.

In reaching its decision, the Second Circuit noted that the government’s construction of speech limitations imposed by the FDCA’s misbranding provisions warranted heightened scrutiny. The Second Circuit compared Caronia to the Supreme Court decision in Sorrell, noting that the government’s construction of the FDCA imposed content- and speaker-based restrictions on speech—i.e., on-label promotion is favored and pharmaceutical companies and their agents may not discuss off-label uses even though those uses are not illegal and others unaffiliated with the company may discuss them.  The Second Circuit then analyzed the government’s construction of the FDCA under the Central Hudson test to determine whether off-label promotional speech is protected by the First Amendment.  The majority opinion concluded that the prohibition of non-misleading and truthful off-label speech was unconstitutionally restrictive.  The court’s Central Hudson analysis appeared broader and more assertive than in Washington Legal Foundation (WLF). Unlike in WLF, the court here discussed the entire FDCA off-label regime. In dicta, the court suggested that the government could address off-label promotion permissibly through educational outreach efforts, disclaimer requirements or, in extreme cases, banning an off-label use, but not by restricting speech.

It will be interesting to see how this decision will affect FDA’s regulatory enforcement and government prosecutions going forward. Although Caronia leaves intact the legal bases for prosecution of off-label promotion, the failure to provide adequate directions for use and prohibition on false or misleading labeling, it raises doubt that oral off-label promotional statements by themselves can be presumptive evidence of a misbranding violation under the FDCA.  This opinion likely will cause the government to alter its approach in future cases, perhaps focusing less on the speech itself and more on whether there is intent to misbrand a product for which the speech provides supporting evidence.

While the Second Circuit acknowledges FDA’s Good Reprint Practice Guidance and suggests in its holding that there could be truthful dissemination, including oral dissemination, of off-label use information by drug companies outside of this context or in follow-up to unsolicited requests, drug manufacturers are unlikely to reevaluate or rewrite their product promotion policies and procedures based on this court’s ruling.  One reason is that understanding what would qualify to the courts or agency as truthful and non-misleading off-label information that also satisfies the adequate directions for use standard remains elusive.  Moreover, the authority in the FDCA to restrict false or misleading product labeling provides FDA with broad enforcement authority in this space for oral or printed claims that misleadingly suggest that there is substantial evidence for an unapproved use, so companies would be wise to maintain current product promotion policies and procedures.

B.   Likely Implications

  • FDA is likely considering whether to appeal this ruling by the Second Circuit Court of Appeals to the U.S. Supreme Court.  FDA may be wary of bringing this issue in the context of a criminal prosecution back to the same court that rendered the expansive Sorrell ruling.  If FDA loses, it could find elements of the Caronia decision expanded nationally.
  • While FDA may still elect to appeal the decision (because FDA is convinced that it is right on the merits), it most likely will issue some form of clarification to the regulated community in the form of a Federal Register Notice, much like the action it took in response to the WLF case (see 65 Fed. Reg. 14,286). 
  • FDA may refine its position on permissible dissemination of off-label information, as it did after the WLF decision in its guidance entitled Good Reprint Practices for Distribution of Medical Journal Articles (Good Reprint Practices).
  • FDA may review the decision narrowly and continue to enforce off-label promotion as either “false or misleading” communications or seize the court’s dicta and prosecute for an intent to misbrand for failure to provide adequate directions for use of the off-label indication/dosage.
  • Manufacturers and their marketing representatives should still refrain from making off-label claims and rely on existing FDA guidance, including Good Reprint Practices and Responding to Unsolicited Requests for Off-Label Information.  This will, likewise, prevent investigations by OIG and subsequent coerced settlements to preserve participation in federal health insurance programs.