Case law decided in 2011 and 2012 created an illusion of security that pharmaceutical manufacturers’ communications regarding medications approved by the Food and Drug Administration (FDA) are protected by the First Amendment. See Sorrell v. IMS Health, Inc., 131 S. Ct. 2653 (2011); United States v. Caronia, 703 F. 3d 149 (2d Cir. 2012). Specifically, these cases stand for the proposition that the Food, Drug and Cosmetic Act (FDCA) could not be interpreted to prohibit truthful, off-label promotion because that type of off-label promotion is commercial speech protected by the First Amendment. The pronouncement in these cases, particularly Caronia, seems clear, but they are in marked contrast to the plain language of the Food and Drug Cosmetic Act (FDCA) as well as FDA guidance documents as to what the companies can and cannot do with respect to off-label promotion. Moreover, Caronia left open the door for the government to use off-label promotion as evidence of a crime of fraud or misbranding. And we have yet to see any decrease in the Justice Department’s off-label investigations or pending settlements for alleged off-label marketing of drugs for uses not yet approved by the Food and Drug Administration (FDA).

1. RECENT CASE LAW ESTABLISHES THAT OFF-LABEL PROMOTION IS FREE SPEECH PROTECTED BY FIRST AMENDMENT

In Sorrell, the United States Supreme Court decided that a Vermont statute that prohibited pharmaceutical companies from using prescriber-identifying information for marketing purposes violated the First Amendment.

Sorrell was used as a stepping stone in the seminal case that has garnered significant attention on the application of the First Amendment to off-label promotion Caronia. In Caronia, the Defendant sales representative was charged with conspiracy to misbrand a medication because he was promoting the medicine for unapproved uses. The jury instruction provided by the district court stated: “A misbranded drug may be shown by a promotion of a drug by a distributor for an intended use different from the use for which the drug was approved by the FDA.” ¹Caronia, 703 F.3d at 158. The Defendant was convicted in the Eastern District of New York for misbranding, specifically promoting an off-label use of an approved prescription drug. The United States Court of Appeals for the Second Circuit vacated and remanded the decision finding that the application of the FDCA’s misbranding provisions to his off-label promotional statements unconstitutionally restricted his right to free speech under the First Amendment. In making its decision, the Court reasoned that the FDCA does not make it a crime or expressly prohibit off-label promotion. Id. at 159; see 21 C.F.R. § 201.128. However, it held that the “The promotion of off-label uses plays an evidentiary role in determining whether a drug is misbranded under 21 C.F.R. § 352(f)(1).” Relying on the Sorrell decision, the Court found that “[s]peech in aid of pharmaceutical marketing … is a form of expression protected by the Free Speech Clause of the First Amendment.” Id. at 161 (citing Sorrell, 131 S. Ct. at 2659 [emphasis in original]). The government did not appeal the Second Circuit’s decision, so we do not know how the Supreme Court would have ruled on this precise issue.

2. CONFLICT WITH FDA REGULATIONS AND GUIDANCES

In the aftermath of Caronia, pharmaceutical companies are left with uncertainty as to best practices to use that are in line with the Caronia holding as well as the FDA rules and regulations. Regulations provide that pharmaceutical manufacturers may lawfully provide off-label use information in accordance with the following: as part of scientific exchange, in response to unsolicited requests, in the context of continuing medical education (CME) and other scientific and educational activities, and in medical journal articles and scientific or medical reference publications disseminated to prescribers and healthcare entities. See 21 C.F.R. §312.7(a); 59 Fed. Reg. 59.820, 59.823; 62 Fed. Reg. 64,074; 74 Fed. Reg. 1,694.

GUIDANCE DOCUMENTS PROVIDE THE FOLLOWING RECOMMENDATIONS:

Draft Guidance for Industry: Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices (December 2011)

This draft guidance provides the FDA’s recommendations to companies wishing to respond to unsolicited requests for off-label information about their products, including both requests made directly and privately to companies and requests made in public forums, including through emerging electronic media. The draft guidance discusses the difference between unsolicited and solicited requests and presents a number of examples of both types of requests. The guidance states that if a company responds to unsolicited requests for off-label information in the manner described in the draft guidance, the FDA does not intend to use such responses as evidence of the firm’s intent that its product be used for an unapproved or uncleared use. Such responses also would not be expected to comply with the disclosure requirements related to promotional labeling and advertising. The FDA advised that companies which choose to respond to unsolicited requests for information about off-label uses of their approved or cleared products in a manner other than that recommended in the draft guidance would not be violating the law per se, but such responses could potentially be introduced as evidence of a new intended use.

See “Draft Guidance for Industry: Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices,” December 2011. Available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM285145.pdf. Last accessed October 22, 2014.

Revised Draft Guidance for Industry: Distributing Scientific and Medical Publications on Unapproved New Uses – Recommended Practices (February 2014)

On March 3, 2014, the FDA issued a new draft guidance allowing manufacturers to distribute journal articles, textbooks and clinical practice guidelines containing information about off-label uses of approved/cleared drugs and medical devices. The draft updates the FDA’s 2009 reprints guidance and represents the first time the FDA has ever acknowledged in a guidance or regulation that it is permissible for a manufacturer to distribute such guidelines, and represents the FDA’s continued effort to respond to the issues raised by the Medical Information Working Group (MIWG) and its member companies in two citizen petitions filed with the FDA in 2011 and 2013.² On June 6, 2014, the FDA granted these Citizen Petitions submitted by the MIWG that requested clarification of the agency’s position on drug and device manufacturer communications concerning investigational products and unapproved uses of approved products. MIWG specifically asked the agency to review its regulations and policies in light of recent First Amendment case law, including the Sorrell and Caronia cases. In its response to the petitions, the agency stated that it has already addressed many of the specific issues raised by MIWG in recent guidance on unsolicited requests (2011); social media (2013); and reprints, reference texts, and clinical practice guidelines (2014). The agency also issued a call for comment on the scope of “scientific exchange” in December 2011. In addition to these initiatives, the FDA reported that it plans to issue two new guidance documents before the end of 2014 – one addressing unsolicited requests, distributing scientific and medical information about unapproved new uses, and manufacturer discussions concerning scientific information more generally, and another on healthcare economic information.

See “FDA Revised Draft Guidance for Industry: Distributing Scientific and Medical Publications on Unapproved New Uses – Recommended Practices,” February 2014. Available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM387652.pdf. Last accessed October 22, 2014.

3. CRIMINAL PROSECUTIONS

To further muddy the issue, pharmaceutical companies have been faced with repeated prosecutions from the government, resulting in massive dollar value settlements, where the focus of the conduct has been off-label promotion. See e.g., United States v. GlaxoSmithKline, LLC, 12-cr-10206, ECF Docket No. 13 (D. Mass. July 10, 2012).

Under the provisions of the Food, Drug and Cosmetic Act, a company in its application to the FDA must specify each intended use of a drug. After the FDA approves the product as safe and effective for a specified use, a company’s promotional activities must be limited to the intended uses that the FDA approved. In fact, promotion by the manufacturer for other uses – known as “off-label uses” – renders the product “misbranded.” Caronia, 703 F.3d. at 154. It is under the theory that off-label use rises to misbranding that prosecutions against companies are resulting in significant charges and settlements. In these criminal matters, the government unlawfully alleges promotion of FDA-approved medications for unapproved indications. For example, the United States will typically allege that, among other things, a company participated in preparing, publishing and distributing misleading medical journal articles that misreported clinical trial information. The Government will then focus on sales activity directed at promoting the medication for unintended uses. Id. However, one could argue that there is a requirement of fraud or falsity required for the government to be successful in prosecuting these types of claims.

4. RECENT DEVELOPMENTS

In April, at the Food and Drug Law Institute Annual Meeting, the FDA senior officials stated that the organization is taking the industry’s concerns seriously that its existing off-label policies are not in line with the most recent First Amendment case law. See Coalition for Healthcare Communication, “FDA Willing to ‘Re-examine’ Off-label Policies in Light of First Amendment Rulings,” April 28, 2014. Available at http://www.cohealthcom.org/2014/04/28/fda-willingto-%E2%80%9Cre-examine%E2%80%9D-off-label-policiesin-light-of-first-amendment-rulings/. Last accessed October21, 2014. Additionally, in a recent California case alleging violation under the False Claims Act, PhRMA filed an amicus brief to support Defendants’ motion to dismiss arguing that the conduct in question, dissemination of published articles, is protected by the First Amendment. See United States ex rel. Solis v. Millennium Pharmaceuticals, Inc., 2014 WL 1270591 E.D. Cal,. Mar. 26, 2014. The thrust of the argument on behalf of the Defendants is that the First Amendment does not permit the criminalization of truthful, off-label promotion.

Until there are additional promulgations from the FDA in the form of guidances, or regulations or further responses to the Citizen Petitions and other requests from industry working groups, we continue to monitor cases and stakeholder positions that may implicate future action in this area. Until this issue is more settled, pharmaceutical manufacturers should remain aware of, and be wary of, the risks of off-label promotion.

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[1] Although the appeal challenged the use of the instruction, the Second Circuit did not reach a decision on that issue because of its ruling related to the restriction on the First Amendment.

[2] See “Citizen Petition,” September 3, 2013 Available at, found at http://www.cohealthcom.org/wp-content/uploads/2013/09/citizen-petition.pdf . Last accessed October 21, 2014.

Finis