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Losing Its Bite? The Erosion of FDA Power Over Promotion of Off-Label Drug Use

Attorney: Katie A. Stricklin | Published 3.17.16

The federal Food, Drug and Cosmetic Act (FDCA) requires drug manufacturers to demonstrate to the Food and Drug Administration (FDA) both the safety and the effectiveness of their drugs for their intended uses in order to obtain approval for distribution to the market  If the FDA approves a drug, the approval extends only to the intended uses of the drug.

The FDCA regulates drug manufacturers.  The FDCA does not regulate doctors.  Thus, although FDA approval of a drug extends only to the intended uses of the drug, a doctor possesses the freedom to prescribe a drug for both its intended uses, i.e., approved uses, or its unintended uses, i.e., nonapproved or “off-label” uses.  The prescription of approved drugs for off-label purposes occurs frequently.  In certain fields, off-label prescribing occurs more frequently than prescribing for approved use.

Despite the practice and potential benefits of off-label use of approved drugs, the FDA admonishes drug manufacturers that market or promote an approved drug for off-label use.  Simply put, until the FDA has approved a drug for a particular use, the manufacturer may not promote the drug for that use.  The FDA staunchly opposes such promotion to the point that it prosecutes drug manufacturers pursuant to a provision in the FDCA that criminalizes the “introduction or delivery for introduction into interstate commerce of any food, drug, device, tobacco product, or cosmetic that is adulterated or misbranded.” This prohibited activity, known as “misbranding,” can result in imprisonment and monetary fines.

Decided just months ago, Amarin Pharma, Inc. 1.1,5- Food & Drug Admin. (S.D.N.Y., Aug, 7, 2015 WL 4720039) was a case involving Amarin Pharma, Inc. (Amarin), a manufacturer of a triglyceride-lowering drug known as Vascepa.  The FDA approved Vascepa for one user to treat adult patients with triglyceride levels above 500 mg/dL of blood, i.e., “very high triglycerides.” Amarin sought FDA approval of Vascepa for an additional use to treat adult patients with triglyceride levels between 200 and 499 mg/dL of blood who are already on strain therapy, i.e., “persistently high triglycerides.”  The FDA did not approve this second use.  Thus, use of Vascepa to treat persistently high triglycerides constituted an unapproved off-label use of Vascepa.

Although the FDA did not approve such use, doctors commonly prescribed Vascepa to treat patients with persistently high triglycerides.  Furthermore, the FDA acknowledged that Vascepa effectively reduced triglyceride levels in a safe manner.

Nevertheless, the FDA warned Amarin that Amarin might violate the misbranding provision of the FDCA if Amarin marketed the off-label use of Vascepa in its communications to healthcare professionals.

Amarin sued the FDA on the grounds that the FDA’s restrictions on off-label promotion constituted an unlawful restraint on speech under the First Amendment.  Amarin contended that the First Amendment protects a manufacturer whose conduct consists solely of truthful and non-misleading speech to promote off-label use of an approved drug.

The determination of the case depended on the interpretation and application of a prior landmark case, United States v. Caronia (2d. Cir. 2012) 703 F.3d 149, in which the Second Circuit held that the misbranding provision of the FDCA cannot be construed as prohibiting and criminalizing the truthful off-label promotion of FDA-approved prescription drugs where the off-label use itself is lawful.

Whereas the FDA argued Caronia was limited to the factual circumstances presented in Caronia, Amarin argued that Caronia had general applicability.  The District Court for the Southern District of New York agreed with Amarin: Caronia was not limited to the facts of that case, and, as a general matter, the FDA may not bring a misbranding action based on truthful promotional speech alone.  The court entered a preliminary injunction in favor of Amarin that prevented the FDA from bringing a misbranding action against Amarin if Amarin began to promote an off-lael use of its triglyceride-lowering drug.


As a result of Caronia and Amarin, drug manufacturers might feel empowered to more aggressively market their drugs.  Although these cases certainly restrict the FDA’s regulatory powers, manufacturers should be mindful of the limitations of these cases.

First, the First Amendment does not protect false or misleading commercial speech.  Thus, a manufacturer cannot use false or misleading communications to promote an off-label use.  The holdings of Caronia and Amarin are limited to truthful and non-misleading statements.

Second, the First Amendment protects expression rather than conduct.  Thus, a manufacturer that engages in noncommunicative activities to promote off-label use can still be prosecuted under the misbranding provisions.

For example, a manufacturer might be subject to a misbranding action if its salesperson pays a doctor money to reward the doctor for prescribing a drug for off-label use.

Finally, a decision by a federal district court does not bind any other court.  Because the Southern District of New York decided Amarin, other district courts might look to Amarin as instructive or persuasive for its holding and its interpretation of Caronia, but they do not need to follow the Amarin mandates.

Practical Tips

The Amarin court advised drug manufacturers to remain prudent in marketing and promotion to avoid unnecessary regulatory attention and legal disputes.  As a matter of practice, a manufacturer would be wise to vet and script in advance its statements about a drug’s off-label use.  If a manufacturer permits its sales representatives to communicate off-the-cuff with a health-care professional rather than require the representative to adhere to a script that contains preapproved statements, the sales representative might inadvertently make false or misleading representations regarding off-label use.  In such a case, the FDA can bring a misbranding action.

A manufacturer should also consider consulting with the FDA prior to disseminating materials that promote off-label use.  Whether a statement is misleading in nature is a question that is open to interpretation.  Consulting with the FDA may prevent misbranding charges regarding statements that the FDA might interpret differently than the manufacturer.  Further, a statement that is not misleading today may be misleading tomorrow by virtue of advancements in science or medicine.