By Anthony J. Anscombe, a Partner resident in the Chicago, IL and San Francisco, CA offices of Sedgwick LLP and Mary Beth Buckley, a Senior Associate resident in the firm’s Chicago office.
Freedom of speech and the protection of public health are cornerstones of American society. But these values have found themselves at odds with each other in the area of so-called off-label promotion of drugs and medical devices.
Regulatory conflicts between medical-product manufacturers and the government over speech regarding off-label uses have been raging for over 20 years. But recent attention has shifted to the federal government’s pursuit of criminal charges against individuals accused of promoting off-label uses. The recent convictions of two Acclarent executives in United States v. Facteau demonstrate the blurry lines that currently separate speech from criminal conduct. The convictions also underscore how speech rights, due process, and public health could be better protected through reform of FDA’s regulatory scheme. Such reform should favor more speech, not less.
FDA Product Review and Off-Label Uses
Under the Food, Drug, and Cosmetic Act (FDCA), medical-product manufacturers are required to obtain premarket approval from FDA prior to marketing a new drug or device.1 The law not only prohibits the sale of unapproved new drugs, but also “adulterated” devices and “misbranded” drugs and devices. Devices are considered “adulterated” if they are not FDA approved.2 Drugs and devices are “misbranded” if their labels do not carry adequate instructions for use.[ note]21 U.S.C. § 352(f).[/note] An FDA regulation adds that label instructions must be adequate for the product’s intended use.[ note]21 CFR § 201.5, § 801.5.[/note] “Intended uses” are those indicated on the FDA-approved product label. Drugs and devices sold with an intent that they be used for off-label indications may therefore be deemed misbranded, adulterated, or both.
The FDCA does not authorize FDA to regulate the practice of medicine. Thus, physicians may freely prescribe drugs and devices for off-label purposes. Indeed, FDA itself has recognized that off-label uses provide important public-health benefits.3
Nevertheless, to preserve the integrity of its premarket approval rules, FDA has forbidden drug and device manufacturers from “promoting” off-label uses.4 It has taken the view that labels lack “adequate instructions for use” when the product is “intended” for a use other than its approved use. And while FDA has recognized that the First Amendment protects promotional speech,5
it posits that medical-product manufacturers may only answer questions posed by medical professionals about off-label uses, and cannot suggest those uses affirmatively.6
The First Amendment and Off-Label Speech
As a general principle, the First Amendment limits government’s ability to regulate truthful, non-misleading commercial speech. Those limits certainly apply to how FDA regulates speech regarding medical products. In fact, the first case in which the US Supreme Court recognized First Amendment protection for commercial speech, Virginia Board of Pharmacy v. Virginia Citizens Consumer Council,7 involved state restrictions on the advertising of drug prices. Since that 1976 decision, the Court has consistently affirmed protection for speech relating to drugs, medical devices, or healthcare information.8
When a challenged regulation discriminates against commercial speech based on its content or on the type of speaker or the speaker’s viewpoint, the Supreme Court has held that it must withstand “heightened scrutiny.” The Court reached this conclusion in IMS Health Inc. v. Sorrell with regard to a Vermont law that prohibited the use of anonymized drug-prescription data for marketing, but allowed virtually all other uses. FDA’s treatment of off-label “promotion,” which specifically targets drug and device makers, is quite analogous to the law invalidated in IMS Health.
At minimum, however, commercial-speech restrictions receive “intermediate”-level scrutiny as the Court prescribed in Central Hudson Gas & Electric v. Public Service Commission.9 Under Central Hudson, in order to regulate speech that is truthful and relates to a legal activity, the state must (1) have a substantial interest in the regulation, (2) the regulation must directly advance that interest, and (3) the regulation should be no more restrictive of speech than necessary to advance the government’s interest.
Over the last several years, medical-product companies and their employees have successfully invoked the First Amendment as a defense to prosecution for allegedly unlawful off-label speech.10 United States v. Caronia,11 issued by the US Court of Appeals for the Second Circuit in 2012, has proved to be the most influential. A federal jury in New York convicted a medical sales representative of conspiring to introduce a misbranded drug into interstate commerce. The government argued that it was not prosecuting Mr. Caronia for the content of his speech, but was instead using his speech as evidence of an intended use of the drug. The Second Circuit rejected the government’s argument and concluded that the jury convicted the defendant based on his truthful speech alone. The court assessed the prosecution under Central Hudson and found that it did not directly or materially advance the state interest in drug safety and was more extensive than necessary. Invoking the doctrine of constitutional avoidance, the court held that the FDCA does not prohibit truthful off-label promotion, and it further held that the government may not prosecute companies or their employees for engaging in such speech.
United States v. Facteau
Background. In April 2015, Federal Bureau of Investigation agents from Boston orchestrated the dawn arrest in California of the former CEO of Acclarent, a medical device manufacturer. A second target, Acclarent’s former vice president of sales, surrendered voluntarily. A grand jury handed down an 18-count indictment charging them, among other things, with conspiracy, securities fraud, wire fraud, fraud on the FDA, and ten counts of distributing adulterated and misbranded medical devices.12
The government contended that Acclarent had fraudulently submitted for clearance under § 510(k) of the Medical Devices Act a device known as the “Stratus.” The device’s intended use was the delivery of saline solution into the nasal cavity of patients with sinusitis. The government alleged that Acclarent actually intended that the device’s primary use would be to deliver medications, specifically steroids, to nasal passages. It accused Acclarent of bypassing premarket approval (PMA) under 21 U.S.C. § 360(e) because it would be too costly and time consuming. In order to avoid the PMA process, Acclarent purportedly represented to FDA that Stratus was a saline-delivery device substantially equivalent to other medical devices already on the market. Once Stratus was approved, the government claimed, the company devoted itself to promoting its off-label use. The government sought to hold the executives legally responsible for the alleged deception.
Trial and Verdicts. The government introduced evidence that Acclarent only trained its sales force on the unapproved use and how to prompt doctors into requesting information on the off-label use. It also introduced evidence that the Stratus did not work well for its labeled use, as saline ran out of the device too fast. The government elicited testimony about internal company discussion of off-label uses and iterative design plans showing proposed use with drugs. It argued that this expressive conduct, including promotional speech, proved Acclarent’s “intended use” of the device for unapproved indications.
The defendants argued that Acclarent never hid from the government its desire to have the product labeled for drug delivery, as this use was disclosed on the patent, and the company made repeated attempts over several years to obtain FDA approval for such a use. They also asserted that Acclarent merely did what many companies do, which is to get a product approved for one use, and then seek approval for additional indications. That some members of the sales force may have gone too far in promoting off-label uses to doctors did not mean that the company as a whole sought to defraud FDA. Defendants also introduced evidence that some doctors did, in fact, use the device effectively with saline.
After three days of deliberation, the jury acquitted the defendants of the felony counts, including attempts to defraud FDA. It did, however, convict both men of ten misdemeanor counts of selling an adulterated and misbranded device.
Legal Issues on Post-Trial Motions. The parties have now completed briefing on the defendants’ post-trial motion for acquittal. Defendants’ central arguments focus on whether the convictions have violated their First Amendment rights and whether the criminal proscriptions on defendants’ conduct were sufficiently clear that the defendants had fair notice of them.
The government has argued that defendants were not convicted for their speech, but rather for their actions—they illegally sold medical devices for an intended use that had not received FDA approval. Relying on the Supreme Court’s decision in Wisconsin v. Mitchell, 508 U.S. 476, 489 (1993), the government has argued that Acclarent’s internal speech and that of its sales representatives merely provided evidence of the device’s intended use, but was not, itself, the criminal conduct. FDA has also argued that the FDCA’s misdemeanor provisions, combined with the “intended use” concept, are not unconstitutionally vague.
Reasons that the Court Should Overturn the Convictions. The linchpin of defendants’ First Amendment arguments is that without considering the speech, their conduct was completely legal. The jury found no fraud. The pursuit of § 510(k) clearance for the use of Stratus with saline solution was lawful. Acclarent could legally sell Stratus to physicians who intended to use it in an off-label manner. What converted these lawful acts into misdemeanor crimes was the attendant speech.
But that speech was itself legal in all instances. Acclarent could speak internally about seeking additional clearances. Acclarent could educate its sales force about off-label uses so that the sales team could answer physician questions knowledgably. Acclarent representatives could make truthful, non-misleading statements about off-label uses. The Facteau case is thus quite different from Wisconsin v. Mitchell, where speech furnished evidence of racial animus (mens rea) that enhanced the seriousness of otherwise clearly illegal conduct. In Facteau, by contrast, speech has formed an indispensable part of the actus reus.
FDA’s vague interpretation of “intended uses” compounds the constitutional infirmity of these convictions. FDA regulations attempt to define what this term means—the “objective intent” of the persons legally responsible for labeling the products.13But how FDA actually determines “intent” lacks the objectivity which the regulations imply. Evidence such as labeling claims and advertisements to purchasers likely suffices, but such conduct was not at issue in Facteau. The use of the word “objective” in relation to “intent” implies a contrast with “subjective”—“subjective intent” for off-label use should not suffice. FDA has also eschewed those portions of its own regulations that announce that it will look to a manufacturer’s knowledge of actual off-label use to determine intent.14
Finally, FDA’s recent recognition that it cannot punish truthful, non-misleading speech would also lead a reasonable manufacturer to conclude that the kinds of speech at issue in Facteau would not put its executives at risk of jail time. The defendants have thus argued with considerable force that medical companies and their employees do not know what is and is not permitted. This lack of certainty runs afoul of Fifth Amendment protections of due process.15
Protecting Speech and Public Health
The Facteau convictions send a harrowing message to drug and device company executives that they can be criminally punished for conduct that was not, in itself, illegal, and that only became illegal based on truthful, non-deceptive expression. Public health and freedom of speech are both areas that will be served by bright lines and clear distinctions between proper and improper conduct. Medical device manufacturers should not fear truthful speech, and neither should FDA. The unimpeded flow of truthful speech helps patients.
The Supreme Court has urged time and again that more speech, not less, is the appropriate remedy when truthful speech has a potentially negative societal impact. FDA fears that off-label promotion will cause physicians to prescribe medications for uses that have not been established by rigorous science, and that industry will no longer have financial incentives to conduct that rigorous science.
The Caronia and Amarin courts, however, pointed out that FDA has numerous tools at its disposal to ensure that medical professionals receive full disclosure of off-label risks. For example, FDA could mandate affirmative statements that it has not reviewed off-label uses and that doctors should proceed with caution.
If FDA can align its regulations and enforcement priorities to focus on preventing promotional speech that misleads physicians, industry should still have substantial financial incentive to seek approval for new product uses. Doctors mediate treatment options, and they are both scientifically sophisticated and concerned about their own potential liability. For these reasons, firms which invest in scientific research in support of new uses that win FDA approval should still enjoy a competitive advantage in the market for medical products.
- 21 U.S.C. § 301, et seq.
- 21 U.S.C. § 351(f).
-  See Draft Guidance for Industry, Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices (FDA, Dec. 2011).
- Id.; see also Amarin Pharma, Inc. v. FDA, 119 F. Supp. 3d 196, 200-09 (S.D.N.Y. 2015).
-  Washington Legal Foundation v. Henney, 202 F. 3d 331, 335-336 (2000) (FDA recognizes that it may not regulate manufacturer speech, although it reserves the right to use speech as evidence of intended use.).
- See Draft Guidance for Industry, Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices (FDA, Dec. 2011).
- Virginia Board of Pharmacy v. Virginia Citizens Consumer Council, 425 U.S. 748 (1976).
- See, e.g., Bolger v. Youngs Drug Products Corp., 463 U.S. 60 (1983); Thompson v. Western States Medical Center, 535 U.S. 357 (2002); Sorrell v. IMS Health Inc., 564 U.S. 552 (2011).
- Central Hudson Gas & Electric v. Public Service Commission, 447 U.S. 557 (1980).
- See, e.g., Amarin, supra note 6; Pacira Pharm., Inc. v. FDA, No. 15-cv-07055 (S.D.N.Y. 2015); United States v. Vascular Solutions, No. 14-cr-926 (W.D. Tex. 2016). [WLF was heavily involved in arguing the Caronia appeal and filed an amicus brief in Amarin—Eds.]
- United States v. Caronia, 703 F.3d 149 (2d Cir. 2012).
- United States v Facteau, No. 15-cr-1076 (D. Mass.), D.E.#1.
- 21 CFR §§ 201.128; 801.4.
-  See 80 Fed. Reg. 57,756 (Sept. 25, 2015) (proposed rule deleting manufacturer’s knowledge of off-label use as a basis for finding off-label “intended use.”).
- Johnson v. United States, 135 S. Ct. 2551 (2015); FCC v. Fox Television Stations, Inc., 132 S. Ct. 2307 (2012).