The most recent assault on FDA’s regulation of off-label promotion came from Congress. In a recent letter to the Secretary of the Department of Health and Human Services (HHS), the House Committee on Energy and Commerce told HHS that it wants to see change. Letter from the Honorable Fred Upton and the Honorable Joseph R. Pitts, Ranking Members of the House Committee on Energy and Commerce, to the Honorable Sylvia Burwell, Secretary of HHS (May 26, 2016) [hereinafter “HEC Letter”]. The Committee wrote to express its “concerns” about the position HHS has taken on FDA regulation of “proactive dissemination of truthful and non-misleading information that is outside the scope of a [medical] product’s FDA-approved labeling.” Id. at 1. Grounded in the proposed changes to the way off-label promotion would be regulated under the 21st Century Cures Act, the Committee challenged the Administration’s view that the 21st Century Cures legislation “could undermine regulatory standards by allowing unproven uses of therapies to be marketed to health care payors as though such uses had been proven safe and effective.” Statement of Administration Policy: H.R. 6 – 21st Century Cures Act (July 8, 2015) (here).
Based on the premise that “scientifically accurate” but off-label information is “critical to optimizing patient care,” the Committee stated that a strict prohibition on manufacturers from proactively providing such information is generally “no longer sound public policy” and does not survive constitutional scrutiny. HEC Letter at 1. The Committee pointed to the numerous cases where courts have found First Amendment protection for truthful and non-misleading speech by pharmaceutical manufacturers, beginning with Sorrell v. IMS Health, 564 U.S. 552 (2011), and continuing with United States v. Caronia, 703 F.3d 149 (2d Cir. 2012), Amarin Pharma, Inc. v. FDA, No. 15 Civ. 3588 (S.D.N.Y. Mar. 8, 2016), Pacira Pharms., Inc. v. FDA, No. 15 Civ. 7055 (S.D.N.Y. Dec. 15, 2015), and United States v. Vascular Sols., Inc., No. 5:14-CR-00926 (W.D. Tex. Feb 26, 2016). After reviewing the key cases in this area, the Committee stated, “[a]s FDA’s authorizing committee, we are increasingly perplexed by the agency’s unwillingness or inability to publicly clarify its current thinking on these issues in a coherent manner.” HEC Letter at 2. The Committee noted that policy on whether and how pharmaceutical and medical device companies are permitted to speak about off-label uses of its products was being made, not by FDA rulemaking or subregulatory guidance, but rather through settlement agreements involving cases like those noted above, which the Committee described as “ad hoc . . . lacking any semblance of consistency and cohesiveness.” Id.
In the HEC Letter, the Committee expressed its belief that HHS and the current Administration are blocking the path to clear policy on off-label promotion. The Committee stated that “it is our understanding that HHS has not allowed FDA to issue its completed draft guidance addressing the scope of permissible ‘scientific exchange’” and further described the Administration as being “reflexively opposed” to policy changes “despite their legal footing continuing to crumble.” Id. at 2, 4.
In a display of its eagerness both to move forward and to establish law in this area, the Committee provided a Discussion Draft of a proposed Amendment to the Federal Food, Drug, and Cosmetic Act (FD&C Act) that would allow pharmaceutical and medical device companies greater freedom to disseminate information about their products that is outside of their products’ labeling. To this end, the Amendment proposes four important changes:
First, the Amendment would narrow the definition of “labeling” to include written, printed, or graphic material that accompanies pharmaceutical products only when such material is required to accompany the products under the FD&C Act of the Public Health Service Act. Discussion Draft of Proposed Amendments to the FD&C Act with respect to communication about drugs and devices, and for other purposes, 114th Cong., at 2 (Jan. 30, 2015) (attached as an addendum to the HEC Letter) [hereinafter “Discussion Draft”]. The FD&C Act currently defines labeling as “all labels and other written, printed, or graphic matter (1) upon any article or any of its containers or wrappers, or (2) accompanying such article.” FD&C Act § 201(m). The term “accompanying” has been interpreted broadly by the U.S. Supreme Court, which held that “[o]ne article or thing is accompanied by another when it supplements or explains it . . . No physical attachment one to the other is necessary. It is the textual relationship that is significant.” Kordel v. United States, 335 U.S. 345, 350 (1948). Confining labeling to include only those materials that are required to accompany medical products would exempt a substantial proportion of materials prepared by or on behalf of a medical products company from the regulatory requirements associated with labeling.
Second, the Amendment would explicitly codify a provision stating that advertising, scientific exchange, and investor communications are not labeling. FDA regulations state that advertisements in both print and broadcast media are subject to the requirements of the FD&C Act. 21 C.F.R. § 202.1(l)(1). The regulations go on to state that “printed, audio, or visual matter descriptive of a drug and references published . . . for use by medical practitioners, pharmacists, or nurses, containing drug information supplied by the manufacturer, packer, or distributor of the drug and which are disseminated by or on behalf of its manufacturer, packer, or distributor are hereby determined to be labeling . . . .” Id. § 202.1(l)(2). Thus, FDA has taken the position that most drug advertisements are labeling and regulated as such, in accordance with the provisions of the FD&C Act and FDA regulations. As noted above, the effect of this change would be to exempt a substantial proportion of materials prepared by or on behalf of a medical products company from regulatory requirements associated with labeling, and thus allow manufacturers greater freedom in advertising their products.
Third, the Amendment would limit the definition of intended use of a medical product to include only “the objective intent of the manufacturer and sponsor . . . or persons acting on the manufacturer’s or sponsor’s behalf, as demonstrated by statements contained in labeling, advertising, or analogous oral statements” but not in accordance with the “actual or constructive knowledge of the manufacturer or sponsor” that the medical product will be used off-label. Discussion Draft at 4. The ability of FDA to allege that a manufacturer has placed a misbranded medical product into interstate commerce, based on the intended use of such product inferred from “the circumstances surrounding the distribution” of the product would be eliminated by the Amendment. Thus, the Amendment curbs both FDA enforcement actions against manufacturers for off-label promotion that otherwise meets the truthful and non-misleading standard as well as civil lawsuits under the federal False Claims Act based on a misbranding theory.
Finally, the Amendment would permit a broad array of scientific exchange. The Amendment expressly provides that scientific exchange would not constitute labeling, advertising, or evidence of a new intended use of a medical product. The Amendment describes scientific exchange as including:
- [D]issemination of scientific findings in scientific or lay media;
- [P]ublication of results of scientific studies;
- [L]etters to the editor . . .;
- [C]ommunications at scientific or medical conferences or meetings;
- [D]issemination of medical or scientific publications, reference texts, or clinical practice guidelines;
- [C]ommunication, both proactive and reactive, of information regarding a manufacturer’s [R&D] efforts;
- [C]ommunication, both proactive and reactive, of scientific, medical, or technical information or findings, including communication of such information by personnel in scientific, medical, or clinical development departments of manufacturers; and
- [C]ommunication, both proactive and reactive, of health care economic and health outcomes information . . . . Id. at 7-8.
The dissemination of such information would be permitted so long as it is supported by “evidence generated in accordance with the scientific method;” includes a “conspicuous and prominent statement” that the use of the product is off-label; and does not include a statement that the product has been demonstrated to be safe and effective for such use. Id. at 6. This non-exhaustive list of activities that would constitute scientific exchange essentially would provide a safe harbor for certain types of off-label information disseminated by manufacturers. Id. at 6-7.
While it is too early to predict the success of the Amendment proposed by the Committee, it is clear that many forces are aligned to provide greater freedom to pharmaceutical and medical device manufacturers in the dissemination of truthful and non-misleading off-label information about their products.