In a split decision today, a panel of the Second Circuit Court of Appeals overturned ― on First Amendment grounds ― the criminal conviction of a pharmaceutical sales representative who had promoted Jazz Pharmaceutical’s Xyrem for off-label use. Caronia.pdf.
As an aside, Xyrem, is also known as gamma-hydroxybutyrate or “GHB.” GHB is a powerful and fast-acting central nervus system depressant that has been subject to abuse as a recreational drug and is classified by the Department of Health and Human Services (HHS) as a “date rape” drug.
Caronia was convicted under 21 U.S.C. § 333(a)(2) which makes misbranding an FDA-licensed drug product criminal. A drug is misbranded if, inter alia, its labeling fails to bear "adequate directions for use," 21 U.S.C. § 352(f), which FDA regulations define as "directions under which the lay[person] can use a drug safely and for the purposes for which it is intended," 21 C.F.R. § 201.5. The Food and Drug Act itself does not expressly prohibit or criminalize off- label promotion, but the FDA’s policy has been to consider off-label promotion as showing intent to misbrand per se in that the label would not have adequate directions for the off-label use.
In overturning Caronia’s conviction, the panel held:
Accordingly, even if speech can be used as evidence of a drug's intended use, we decline to adopt the government's construction of the FDCA's misbranding provisions to prohibit manufacturer promotion alone as it would unconstitutionally restrict free speech. We construe the misbranding provisions of the FDCA as not prohibiting and criminalizing the truthful off-label promotion of FDA- approved prescription drugs. Slip Op. at 51.
The panel majority reasoned that the pharmaceutical company’s First Amendment rights to speak about off-label uses is not trumped by any legitimate governmental purpose under Constitutional standards. In fact, the panel made much of the fact that off-label prescription is not illegal and emphasized that as a result, the dissemination of truthful information about off-label uses has positive effects:
As off-label drug use itself is not prohibited, it does not follow that prohibiting the truthful promotion of off-label drug usage by a particular class of speakers would directly further the government's goals of preserving the efficacy and integrity of the FDA's drug approval process and reducing patient exposure to unsafe and ineffective drugs. Slip Op. at 42-42.
It was the majority’s opinion that criminalizing off-label promotion is an ineffective means to achieve the FDA’s mission:
If the government's objective is to shepherd physicians to prescribe drugs only on-label, criminalizing manufacturer promotion of off-label use while permitting others to promote such use to physicians is an indirect and questionably effective means to achieve that goal. Thus, the government's construction of the FDCA's misbranding provisions does not directly advance its interest in reducing patient exposure to off-label drugs or in preserving the efficacy of the FDA drug approval process because the off-label use of such drugs continues to be generally lawful. Accordingly, the government's prohibition of off-label promotion by pharmaceutical manufacturers "provides only ineffective or remote support for the government's purpose." Slip Op. at 47.
One panel judge, Debra Ann Livingston, strongly dissented from the holding. She emphasized the long enforcement against off-label promotion and disagreed with the majority’s Constitutional reasoning. This decision can be appealed to the entire Second Circuit sitting en banc, and/or the U.S. Supreme Court.
Enforcement against off-label promotion is a huge aspect of FDA regulatory power, and a major concern of pharma companies. Many companies have paid fines in excess of a billion dollars to settle off-label marketing prosecutions. Indeed, in 2007, Caronia’s employer, Jazz Pharmaceuticals, itself paid a $20 million settlement for off-label promotion of Xyrem. Hence, companies heavily invest in compliance strategies to avoid prosecution, and are heavily limited in the means they have to convey information about their drugs.
It will be fascinating to see whether other courts follow the Caronia decision, and whether pharma companies alter their promotional techniques as a result of this case or its aftermath.