United States v. Caronia: A Victory for Free Speech vs. Off Label Promotion

The United States Court of Appeals for the Second Circuit (New York), in a 2-1 opinion, vacated the criminal conviction of a pharmaceutical sales representative who was found guilty of conspiracy to introduce a misbranded drug, under the Food, Drug & Cosmetic Act (FDCA), because he spoke about off-label uses of a particular drug.  The government used recorded conversations between the sales reps and doctors to bring the criminal action.  The case is United States v. Caronia. 

As we have written several times, the Food, Drug & Cosmetic Act (FDCA) allows companies to promote their drugs for only intended uses approved by the agency.  While doctors may prescribe and patients may take drugs for unapproved or off-label uses, and private and government payors frequently reimburse such uses, pharmaceutical companies had been prohibited from promoting such uses directly to healthcare providers.  

The court held “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 landmark ruling, which based much of its reasoning off the United States Supreme Court Case IMS v. Sorrell, is a tremendous victory for the life sciences industry, and may have a significant impact on the way the Food and Drug Administration (FDA) and other federal health agencies continue to enforce the misbranding and adulteration provisions of the FDCA.  Off-label promotion has been at the heart of almost every major settlement between pharmaceutical companies, the Department of Justice (DOJ) and the Office of the Inspector General (OIG) for the Department of Health and Human Services (HHS). 

While technically the court’s ruling only applies to State’s located in the 2^nd Circuit, the opinion is likely to provide fuel to many companies who are currently in various stages of investigations or negotiations with the federal government regarding alleged off-label promotion.  Mr. Caronia’s attorney, Thomas Liotti, described the decision to the Wall Street Journal as “a very broad ruling on First Amendment grounds.”  He told Reuters that the decision “increases the marketability of drugs, and means consumers can be fully informed by sales representatives, manufacturers and their own physicians.” 

Michael Carvin, an attorney representing the Washington Legal Foundation (WLF) on Mr. Caronia’s behalf, said, “The opinion quite clearly says the FDA regulatory scheme is unconstitutional.”   “By prosecuting those engaged in truthful speech about off-label uses of medical products, the federal government has significantly hindering health care delivery in this country,” said WLF Chief Counsel Richard Samp following the court’s decision.  “Off-label use is essential to good medical practice because the medical community’s knowledge of the drug effectiveness inevitably outpaces the painstaking FDA approval process for label changes.  In many circumstances off-label use is standard-of-care medicine,” Samp said. 

“Most if not all of these cases have been based on a central premise: that it is unlawful for a company and one of its employees to be promoting a drug or a medical device off-label,” said John R. Fleder, a director at the law firm Hyman, Phelps & McNamara, speaking to the New York Times.  “And this decision hits at the heart of the government’s theory.”

Gerald Masoudi, a former chief counsel of FDA, said the ruling made a distinction between truthful discussion of off-label uses of drugs, many of which are considered legitimate by the medical community, and those that are misleading or false.  He noted that “anyone on the planet” could discuss off-label uses of drugs, except for pharmaceutical companies.  “It’s very significant,” he said, “because it’s going to make FDA, in its promotion cases, focus on the kinds of speech that are more likely to harm consumers, such as false or misleading marketing versus something that is not approved.”

The Pharmaceutical Research and Manufacturers of America, said it was pleased with the ruling. “PhRMA believes that truthful and nonmisleading communication between biopharmaceutical companies and health care professionals is good for patients, because it facilitates the exchange of up-to-date and scientifically accurate information about new treatments,” the statement said.

“FDA is not going to roll over and play dead on this,” said John Kamp of the Coalition for Healthcare Communication, predicting a long slog through the courts.  “It’s too important to them—it attacks the basis of most promotional regulation by FDA.”  Below is a summary of the facts and legal background of the case, and an in-depth discussion of the opinion. 

Factual Background 

The alleged off-label conduct in this case centered on a drug called Xyrem, manufactured by Orphan Medical, Inc. (Orphan), now known as Jazz Pharmaceuticals, which is a specialty pharmaceutical company focused on identifying, developing, and commercializing products to treat pain, sleep disorders and central nervous system disorders.  Xyrem is a sleep inducing depressant whose principal ingredient was gamma-hydroxybutyrate (“GHB”).  Xyrem was first approved by FDA in July 2002 to treat patients with narcolepsy who experience episodes of cataplexy, a condition associated with weak and paralyzed muscles.  In  November 2005, FDA approved Xyrem to treat excessive daytime sleepiness (“EDS”) in patients with narcolepsy. Xyrem is not approved for any other medical indications. 

Abuse of Xyrem can lead to dependence and withdrawal symptoms as well as medical roblems including seizures, coma, and death.  Due to the FDA’s concerns over Xyrem’s potential serious risks, FDA required, prior to approval, that Xyrem’s label include a “black box” warning.  In addition, distribution of Xyrem was restricted and subject to several conditions.  For example, Orphan only distributed it through a single, centralized pharmacy, was required to provide physician and patient education, maintain a physician and patient registry, track prescription usage and detail patient surveillance. 

In April 2005 FDA’s Office of Criminal Investigations, Special Prosecutions Staff, pened a criminal investigation of alleged off-label promotion of Xyrem.  As part of its investigation, the government used a physician as an undercover cooperating witness to determine if the allegations were true.  The government charged that on October 26, 2005, Caronia promoted several off-label uses of Xyrem including fibromyalgia, EDS, muscle disorders, chronic pain and fatigue to its undercover witness.  The government further alleged that, on November 2, 2005, Caronia introduced to the undercover witness another Orphan-paid physician who also promoted Xyrem for off-label indications, including fibromyalgia, EDS, sleepiness, weight loss and chronic fatigue. 

Pursuant to its misbranding regulations, the U.S. government filed a two-count misdemeanor information against Caronia.  Count one of alleged that, between March 2005 and March 2006, Caronia knowingly and intentionally conspired with others to misbrand a drug by marketing Xyrem for off-label uses in violation of 21 U.S.C. §§ 331(a), (k), 333(a)(1) and 18 U.S.C. § 371. Count two charged Caronia with a substantive violation of misbranding a drug while it was held for sale after shipment in interstate commerce, violating 21 U.S.C. §§ 331(k) and 333(a)(1).  Orphan, and another physician involved in the alleged misconduct were also charged under the misbranding provisions of the FDCA; both pled guilty. 

Procedural and Legal Background 

Caronia moved to dismiss on several bases, including that the misbranding provisions of the FDCA violated the Free Speech Clause of the First Amendment.  The Caronia Court quickly rejected Caronia’s first two arguments in support of his motion to dismiss. But, the Court spent considerable analysis on Caronia’s First Amendment argument as the constitutional issues raised by Caronia were “very much unsettled, not only in this circuit but nationwide.”  Nevertheless, the U.S. District Court for the Eastern District rejected Caronia’s First Amendment arguments, instead finding that the FDCA’s prohibition against off label promotion was a reasonable fit for the government’s interest in protecting the public health.   

During the jury trial, the government argued repeatedly that Caronia was guilty because he, with others, conspired to promote and market Xyrem for off-label use.  The “government’s theory of prosecution identified Caronia’s speech alone as the proscribed conduct,” the 2nd Circuit wrote.  Moreover, “The district court, in its jury charge, reinforced the idea that Caronia’s promotional speech was enough to support a guilty verdict.”  The jury convicted Caronia of conspiring to introduce a “misbranded” drug into interstate commerce. 

Caronia appealed his 2009 conviction to the 2^nd Circuit, arguing that he was convicted for his speech — for promoting an FDA-approved drug for off-label use — in violation of his right of free speech under the First Amendment.  During the appeal, the U.S. Supreme Court issued its opinion in IMS v. Sorrell.  As a result, the 2nd Circuit called on Caronia and the government to re-brief the matter based on the Sorrell case.   

On appeal, Caronia principally argued that the misbranding provisions of the FDCA prohibit off-label promotion, and therefore, unconstitutionally restrict speech.8 Caronia argues that the First Amendment does not permit the government to prohibit and criminalize a pharmaceutical manufacturer’s truthful and non-misleading promotion of an FDA-approved drug to physicians for offlabel use where such use is not itself illegal and others are permitted to engage in such speech. 

Thus, the issue on appeal was “whether the government’s prosecution of Caronia under the FDCA only for promoting an FDA-approved drug for off-label use was constitutionally permissible. 

Reasoning 

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 the “promotion” or “marketing” of drugs for off-label use.  Rather, the FDCA and FDA regulations reference “promotion” only as evidence of a drug’s intended use. See 21 U.S.C. § 201.128 (discussing how drug’s intended use can be demonstrated).  Thus, under the principle of constitutional avoidance, the court construed the FDCA as not criminalizing the simple promotion of a drug’s off-label use because such a construction would raise First Amendment concerns.   

The regulations do recognize that promotional statements by a pharmaceutical company or its representatives can serve as proof of a drug’s intended use. See 21 C.F.R. § 201.5.  Off-label promotional statements could thus presumably constitute evidence of an intended use of a drug that the FDA has not approved.  The FDA, however, has concluded that “[a]n approved drug that is marketed for an unapproved use (whether in labeling or not) is misbranded because the labeling of such drug does not include ‘adequate directions for use.'” (quoting 21 U.S.C. § 352(f)); see also Gov’t Br. 48 n.18 (contending no set of directions can constitute adequate labeling for drug’s off-label use).  Thus, the government has treated promotional speech as more than merely evidence of a drug’s intended use — it has construed the FDCA to prohibit promotional speech as misbranding itself. 

Speech versus Evidence of Intent 

The government argued that the First Amendment is not implicated in this case.  Specifically, the government argued that “[p]romoting an approved drug for off-label uses is not itself a prohibited act under the FDCA” and “the promotion of off-label uses plays an evidentiary role in determining whether a drug is misbranded under 21 U.S.C. § 352(f)(1).”   The government contended that Caronia was not prosecuted for his speech, but that Caronia’s promotion of Xyrem for off-label use served merely as “evidence of intent,” or evidence that the “off-label uses were intended ones[] for which Xyrem’s labeling failed to provide any directions.”  Even assuming the government could offer evidence of a defendant’s off-label promotion to prove a drug’s intended use and, thus, mislabeling for that intended use, “that is not what happened in this case,” the court wrote.

First, the government’s contention that it did not prosecute Caronia for promoting the off-label use of an FDA approved drug was belied by its conduct and arguments at trial. Citing the trial record, “The government repeatedly argued that Caronia engaged in criminal conduct by promoting and marketing the off-label use of Xyrem, an FDA-approved drug,” and Caronia “was, in fact, prosecuted and convicted for promoting Xyrem off-label.” 

Second, the government’s assertion that it used Caronia’s efforts to promote Xyrem for off-label use only as evidence of intent “is simply not true.”  Even if the government could have used Caronia’s speech as evidence of intent, the district court record clearly showed “that the government did not so limit its use of that evidence.”  The government never (1) argued in summation or rebuttal that the promotion was evidence of intent; (2) suggested that Caronia engaged in any form of misbranding other than the promotion of the off-label use of an FDA-approved drug; (3) suggested, for example, that Caronia conspired to place false or deficient labeling on a drug.  Rather, the record makes clear that the government prosecuted Caronia for his promotion and marketing efforts. 

Third, the government’s summation and the district court’s instruction left the jury to understand that Caronia’s speech was itself the proscribed conduct.  The district court flatly stated to the jury that pharmaceutical representatives are prohibited

from engaging in off-label promotion.  This specific instruction — together with the government’s summation — would have led the jury to believe that Caronia’s promotional speech was, by itself, determinative of his guilt. 

Fourth, the government clearly prosecuted Caronia for his words –- for his speech.

A pharmaceutical representative’s promotion of an FDA-approved drug’s off-label use is speech.  As the Supreme Court has held: “Speech in aid of pharmaceutical marketing . . . is a form of expression protected by the Free Speech Clause of the First Amendment.”

Sorrell v. IMS Health, Inc.  Here, the proscribed conduct for which Caronia was prosecuted was precisely his speech in aid of pharmaceutical marketing.  Accordingly, we conclude that the government did prosecute Caronia for his speech, and we turn to whether the prosecution was permissible. 

The Prosecution of Caronia’s Speech 

While the government and the FDA construed the FDCA’s misbranding provisions to prohibit off-label promotion by pharmaceutical manufacturers, the FDCA itself does not expressly prohibit or criminalize off-label promotion.  The FDCA defines misbranding in terms of whether a drug’s labeling is adequate for its intended use, and permits the government to prove intended use by reference to promotional statements made by drug manufacturers or their representatives.  Assuming that this approach to the use of evidence of speech is permissible, “it affords little support to the government on this appeal because Caronia was not prosecuted on this basis.”  Rather, the government’s theory of prosecution identified Caronia’s speech alone as the proscribed conduct. 

The court declined the government’s invitation to construe the FDCA’s misbranding provisions to criminalize the simple promotion of a drug’s off-label use by pharmaceutical manufacturers and their representatives because such a construction — and a conviction obtained under the government’s application of the FDCA — would run afoul of the First Amendment. 

Applicable First Amendment Doctrine 

The First Amendment protects against government regulation and suppression of speech on account of its content.  Non-content-based regulation and regulation of commercial speech — expression solely related to the economic interests of the speaker and its audience — are subject to intermediate scrutiny.  Criminal regulatory schemes, moreover, warrant even more careful scrutiny. 

In applying these principles, the 2nd Circuit relied on Sorrell, where the Vermont Prescription Confidentiality Law (the “VPCL”) prohibited pharmaceutical companies and similar entities from using prescriber-identifying information for marketing purposes; it was challenged on First Amendment grounds.  The Court held that the Vermont statute set forth content- and speaker-based restrictions, and that the statute was therefore subject to heightened scrutiny.  Because the VPCL disfavored speech with a particular content (marketing) when expressed by certain disfavored speakers (pharmaceutical manufacturers), the Court held that it unconstitutionally restricted speech.  

In reaching this conclusion, Sorrell engaged in a two-step inquiry.  First, the Court considered whether the government regulation restricting speech was content- and speaker-based.  The Court held that it was; the regulation was therefore subject to heightened scrutiny and was “presumptively invalid.”  

Second, the Court considered whether the government had shown that the restriction on speech was consistent with the First Amendment under the applicable level of heightened scrutiny.  The Court did not decide the level of heightened scrutiny to be applied, that is, strict, intermediate, or some other form of heightened scrutiny.  Rather, after observing that “[i]n the ordinary case, it is all but dispositive to conclude that a law is content based,” the Court concluded that the Vermont statute was unconstitutional even under the lesser intermediate standard set forth in Central Hudson.  The Court further observed that the “outcome is the same whether a special commercial speech inquiry or a stricter form of judicial scrutiny is applied.”  

In considering whether the government had shown that the restriction on speech was consistent with the First Amendment, the Sorrell Court turned to Central Hudson, which sets forth a four-part test to determine whether commercial speech is protected by the First Amendment.   

First, as a threshold matter, to warrant First Amendment protection, the speech in question must not be misleading and must concern lawful activity.  Second, to justify regulations restricting speech, the asserted government interest must be substantial.  Third, the regulation must directly advance the governmental interest asserted,  “to a material degree,”  “[A] commercial speech regulation ‘may not be sustained if it provides only ineffective or remote support for the government’s purpose.'”  Fourth, the regulation must be “narrowly drawn,” and may not be more extensive than necessary to serve the interest.  The government cannot “completely suppress information when narrower restrictions on expression would serve its interests as well.”  “Under the commercial speech inquiry, it is the [government’s] burden to justify its content-based law as consistent with the First Amendment.” 

Application of Sorrell and Central Hudson to Caronia 

Using the two-step analysis from Sorrell, the 2nd circuit first concluded “that the government’s construction of the FDCA’s misbranding provisions imposes content- and speaker-based restrictions on speech subject to heightened scrutiny.”  Second, the court concluded that “the government cannot justify a criminal prohibition of off-label promotion even under Central Hudson‘s less rigorous intermediate test.” 

First, the government’s interpretation of the FDCA’s misbranding provisions to prohibit off-label promotion is content-based because it distinguishes between “favored speech” and “disfavored speech on the basis of the ideas or views expressed.”  Under this construction, speech about the government-approved use of drugs is permitted, while certain speech about the off-label use of drugs — that is, uses not approved by the government — is prohibited, even though the off-label use itself is not. See 21 U.S.C. §§ 331(a), 333(a)(2).  Indeed, the content of the regulated speech drives this construction of the FDCA; as in Sorrell, the “express purpose and practical effect” of the government’s ban on promotion is to “diminish the effectiveness of [off-label drug] marketing by manufacturers.” 

Second, this construction is speaker-based because it targets one kind of speaker – pharmaceutical manufacturers — while allowing others to speak without

restriction.  In Sorrell, pharmaceutical companies were barred from obtaining and using prescriber-identifying information for marketing purposes, but a wide range of other speakers, including private and academic researchers, could acquire and use the information.  

Similarly, here, “because off-label prescriptions and drug use are legal, the government’s application of the FDCA permits physicians and academics, for example, to speak about off-label use without consequence, while the same speech is prohibited when delivered by pharmaceutical manufacturers.”  This construction “thus has the effect of preventing [pharmaceutical manufacturers] — and only [pharmaceutical manufacturers] — from communicating with physicians in an effective and informative manner.” 

Additionally, a claim to First Amendment protection “here is more compelling than in Sorrell because this case involves a criminal regulatory scheme subject to more careful scrutiny.”  Accordingly, the government’s construction of the FDCA’s misbranding provisions to prohibit and criminalize off-label promotion is content- and speaker-based, and subject to heightened scrutiny under Sorrell 

Central Hudson 

The 2nd Circuit found the first two prongs of Central Hudson were easily satisfied.  First, promoting off-label drug use concerns lawful activity (off-label drug use), and the promotion of off-label drug use is not in and of itself false or misleading. 

Second, the government’s asserted interests in drug safety and public health are substantial.  Specifically, the government asserts an interest in preserving the effectiveness and integrity of the FDCA’s drug approval process, and an interest in reducing patient exposure to unsafe and ineffective drugs. 

The third and fourth prongs of Central Hudson require that the regulation directly advance the government’s interests and be narrowly drawn.  The court concluded that “The government’s construction of the FDCA as prohibiting off-label promotion does not, by itself, withstand scrutiny under Central Hudson‘s third prong.” 

First, off-label drug usage is not unlawful, and the FDA’s drug approval process generally contemplates that approved drugs will be used in off-label ways.  In effect, even if pharmaceutical manufacturers are barred from off-label promotion, physicians can prescribe, and patients can use drugs for off-label purposes.  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.” See Sorrell, 131 S. Ct. at 2668-69 (holding government interest in protecting physician privacy not directly served when law made prescriber-identifying information available to “all but a narrow class of disfavored speakers”). 

Second, prohibiting off-label promotion by a pharmaceutical manufacturer while simultaneously allowing off-label use “paternalistically” interferes with the ability of physicians and patients to receive potentially relevant treatment information; such barriers to information about off-label use could inhibit, to the public’s detriment, informed and intelligent treatment decisions. see also Sorrell, 131 S. Ct. at 2670-72 (“[The] fear that [physicians, sophisticated and experienced customers,] would make bad decisions if given truthful information” cannot justify content-based burdens on speech.”)  The First Amendment directs us to be especially skeptical of regulations that seek to keep people in the dark for what the government perceives to be their own good.”). 

In fact, in granting safe harbor to manufacturers by permitting the dissemination of off-label information through scientific journals, the FDA itself “recognizes that public health can be served when health care professionals receive truthful and non-misleading scientific and medical information on unapproved uses” of approved drugs. (citing Dep’t of Health and Human Serv., Good Reprint Practices; see Wash. Legal Found. v. Henney, 202 F.3d 331, 335 (D.C. Cir. 2000) (discussing FDA “safe harbor,” where certain forums for off-label discussion, such as continuing medical education programs and scientific publications, would not be used against manufacturers in misbranding enforcement actions). 

Here, as the FDA recognizes, it is the physician’s role to consider multiple factors, including a drug’s FDA approval status, to determine the best course of action for her patient.  see also Thompson, 535 U.S. at 367 (discussing the “general rule” that “the speaker and the audience, not the government, assess the value of the information presented“).   

While some off-label information could certainly be misleading or unhelpful, “this case does not involve false or misleading promotion.”  Moreover, in the fields of medicine and public health, “where information can save lives,” it only furthers the public interest to ensure that decisions about the use of prescription drugs, including off-label usage, are intelligent and well-informed (quoting Sorrell). 

The government did not contend that off-label promotion was in and of itself false or misleading, and the court recognized that “off-label promotion that is false or misleading is not entitled to First Amendment protection.”  Under 21 U.S.C. § 331(a), a defendant may be prosecuted for untruthfully promoting the off-label use of an FDA-approved drug, e.g., making false or misleading statements about a drug.  The government did not argue at trial, nor on appeal, that the promotion in question was false or misleading.   

“The government’s construction of the FDCA essentially legalizes the outcome — off-label use – but prohibits the free flow of information that would inform that outcome. 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.”  

The last prong of Central Hudson requires the government’s regulation to be narrowly drawn to further the interests served.  Here, the government’s construction of the FDCA to impose a complete and criminal ban on off-label promotion by pharmaceutical manufacturers “is more extensive than necessary to achieve the government’s substantial interests.”  The court noted that “Numerous, less speech-restrictive alternatives are available, as are non-criminal penalties.”  To advance the integrity of the FDA’s drug approval process and increase the safety of off-label drug use, the government could pursue several alternatives without excessive First Amendment restrictions.  

For example, if the government is concerned about the use of drugs off-label, it could more directly address the issue.  If the government is concerned that off-label promotion may mislead physicians, it could guide physicians and patients in differentiating between misleading and false promotion, exaggerations and embellishments, and truthful or non-misleading information. The government could develop its warning or disclaimer systems, or develop safety tiers within the off-label market, to distinguish between drugs.  The government could require pharmaceutical manufacturers to list all applicable or intended indications when they first apply for FDA approval, enabling physicians, the government, and patients to track a drug’s development. 

To minimize off-label use, or manufacturer evasion of the approval process for such use, the government could create other limits, including ceilings or caps on off-label prescriptions.  The FDA could further remind physicians and manufacturers of, and even perhaps further regulate, the legal liability surrounding off-label promotion and treatment decisions.  Finally, where off-label drug use is exceptionally concerning, the government could prohibit the off-label use altogether. See, e.g., Bader, 678 F.3d at

873-75 & n.10 (citing 21 U.S.C. § 333(e) (prohibiting off-label use of human growth hormone)). The possibilities are numerous indeed. 

“If the First Amendment means anything, it means that regulating speech must be a last — not first — resort.”  The government has not established a “reasonable fit” among its interests in drug safety and public health, the lawfulness of off-label use, and its construction of the FDCA to prohibit off-label promotion.  The government’s interests could be served equally well by more limited and targeted restrictions on speech.  

The government argued that these alternative means of reducing patient exposure to unsafe, untested drugs and maintaining the integrity of the FDA-approval process are “indefensible”, because they are not administrable, feasible, or otherwise effective.  In the absence of any support, such conclusory assertions are insufficient to sustain the government’s burden of demonstrating that the proposed alternatives are less effective than its proposed construction of the FDCA in furthering the government interests identified.  Accordingly, even if speech can be used as evidence of a drug’s intended use, the court declined to adopt the government’s construction of the FDCA’s misbranding provisions to prohibit manufacturer promotion alone as it would unconstitutionally restrict free speech.   

The court construed the misbranding provisions of the FDCA as not prohibiting and criminalizing the truthful off-label promotion of FDA approved prescription drugs.  The court’s conclusion “is limited to FDA-approved drugs for which off-label use is not prohibited,” and the court did not hold, “that the FDA cannot regulate the marketing of prescription drugs.”  The court simply concluded “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 court posed an interesting hypothetical, but did not address it because the facts of Caronia did not implicate them.  The court noted how it “remains unclear how the government would identify criminal misbranding from communications between drug manufacturers and physicians authorized to prescribe drugs for off-label use.  For example, would a manufacturer be guilty of misbranding if it ships Xyrem to a doctor who, in placing his order, reveals that he prescribes the drug for off-label use — on a theory that the manufacturer now knows that the drug is not properly labeled for that use — but not if the manufacturer ships to a doctor who does not reveal that he prescribes the drug off-label?   

Dissent 

The lone dissenting judge, Judge Debra Ann Livingston, vigorously disagreed, arguing that by throwing out Mr. Caronia’s conviction “the majority calls into question the very foundations of our century-old system of drug regulation.” She argued that if drug companies “were allowed to promote F.D.A.-approved drugs for nonapproved uses, they would have little incentive to seek F.D.A. approval for those uses.”