- From LexisNexis® Mealey’s™ Daily Legal News.
The federal government’s criminal prosecution of a sales representative’s off-label promotion of a drug is unconstitutional under the First Amendment right of free speech, a panel of the Second Circuit U.S. Court of Appeals said Dec. 3 in a 2-1 ruling (United States of America v. Alfred Caronia, No. 09-5006, 2nd Cir.; 2012 U.S. App. LEXIS 24831).
In 2005, Alfred Caronia was hired by Orphan Medical Inc. (now Jazz Pharmaceutical) to promote Xyrem, a depressant whose active ingredient is gamma-hydroxybutryate (GHB, also known as the “date rape drug”). Xyrem was approved by the Food and Drug Administration to treat narcolepsy patients for cataplexy and excessive daytime sleepiness.
The drug carried a black box warning that its safety and effectiveness for children under 16 and for the elderly was not established. Its national distribution was restricted to one pharmacy.
That year, Caronia started a speakers’ bureau and hired Dr. Peter Gleason as a speaker. That same year, the federal government began investigating Orphan and Gleason and recorded Caronia and Gleason promoting Xyrem for off-label uses.
In 2007, the government indicted Caronia for conspiracy to introduce a misbranded drug into interstate commerce in violation of the Federal Food, Drug and Cosmetic Act (FDCA). Orphan and Gleason were also charged and pleaded guilty.
Caronia’s argument that his indictment was an unconstitutional restriction of his free speech right was rejected and the case went to trial in 2008. The jury found that Caronia was guilty of conspiracy to introduce misbranded Xyrem into interstate commerce, but it found him not guilty for “Conspiracy to do an act with respect to a drug, Xyrem, when such drug was held for sale after shipment in interstate commerce when such act would result in Xyrem being misbranded.”
Caronia was sentenced to one year of probation, 100 hours of community service and a $ 25 special assessment.
Majority Takes Narrow View
Caronia appealed, arguing that the misbranding provisions of the FDCA prohibit off-label promotion and therefore unconstitutionally restrict speech. He argued that First Amendment does not prohibit and criminalize a drug maker’s truthful and nonmisleading promotion of FDA-approved drugs for legal but off-label use.
The majority took a narrower view than Caronia: “While the FDCA makes it a crime to misbrand or conspire to misbrand a drug, the statute and its accompanying regulations do not expressly prohibit or criminalize off-label promotion,” the majority said. “Rather, the FDCA and FDA regulations reference ‘promotion’ only as evidence of a drug’s intended use.”
“Thus, under the principle of constitutional avoidance, explained infra, we construe the FDCA as not criminalizing the simple promotion of a drug’s off-label use because such a construction would raise First Amendment,” the majority wrote. “Because we conclude from the record in this case that the government prosecuted Caronia for mere off-label promotion and the district court instructed the jury that it could convict on that theory, we vacate the judgment of conviction.”
Alternative Enforcement Available
The majority said the government could enforce its drug promotion regulations through noncriminal penalties and alternative that don’t restrict free speech. It said the government can “guide” physicians and patients to differentiate between misleading and false promotion, exaggerations and embellishments and between truthful or nonmisleading information.
The government can also develop warning or disclaimer systems to develop “safety tiers within the off-label market” to distinguish between drugs, the majority said. Another alternative would be to require drug makers to list all applicable or intended uses for drugs when they apply for FDA approval.
To minimize off-label use or “manufacturer evasion,” the majority said that the government could create “ceilings or caps on off-label prescriptions.” It said the FDA could remind physicians and drug makers of the “legal liability surrounding off-label promotion and treatment decision.”
Finally, the majority said that when off-label use is “exceptionally concerning,” the government would prohibit off-label use altogether.
“We construe the misbranding provisions of the FDCA as not prohibiting and criminalizing the truthful off-label promotion of FDA-approved prescription drugs,” the majority concluded. “Our conclusion is limited to FDA-approved drugs for which off-label use is not prohibited, and we do not hold, of course, that the FDA cannot regulate the marketing of prescription drugs.”
“We conclude simply that the government cannot prosecute pharmaceutical manufacturers and their representatives under the FDCA for speech promoting the lawful, off-label use of an FDA-approved drug,” the majority said in remanding the case to the District Court.
Circuit Judge Denny Chin wrote the opinion. Joining him was Circuit Judge Reena Raggi.
Dissent: Drug Regulation Threatened
Circuit Judge Debra Ann Livingston dissented, saying, “the First Amendment has never prohibited the government from using speech as evidence of motive or intent.”
“By holding, instead, that Caronia’s conviction must be vacated – and on the theory that whatever the elements of the crime for which he was duly tried, he was in fact convicted for promoting a drug for unapproved uses, in supposed violation of the First Amendment – the majority calls into question the very foundations of our century-old system of drug regulation. I do not believe that the Supreme Court’s precedents compel such a result.”