Citing violations of the APA and what they call the establishment of a “new and unjustified legal standard,” a coalition of industry groups is requesting the FDA indefinitely stay the rule. In a petition to the FDA, the groups raise concerns about the FDA’s backpedaling on claims it would rein in its oft-contentious definition of intended uses.

The Medical Information Working Group, PhRMA and BIO jointly filed a petition calling on the FDA to stay its final rule on intended use over concerns about alterations the rule would make to the legal concept of intended use. The groups criticize the FDA for not sufficiently communicating with the public before finalizing revisions to the intended use definition for drugs and medical devices as well as establishing a new “totality of evidence” standard.

Since these substantial changes were not communicated to the public before the final rule was published on Jan. 9, the groups argue they were deprived of fair notice and a chance to voice their opinion – a violation of the Administrative Procedure Act. The APA requires the FDA to make its views known to the public in a way that permits criticism or formulation of alternatives. Though proposed and final rules don’t need to be totally identical, the petitioners claim they may only differ if the final version is a “logical outgrowth” of the proposed version. In this case, they say, the changes to the proposed rule are substantial, and the FDA failed to provide sufficient notice “of a fundamental change to the regulatory scheme for drugs and devices.”

The petition also calls into question the FDA’s updated definition of intended use, saying it contradicts the statutory definitions in the Federal Food, Drug, and Cosmetic Act and the mandate that drug and device labeling bear adequate directions for use. Citing committee reports from 1934 and 1935, the groups argue the FDCA made clear that intended use would be based on representations by the manufacturer, meaning a manufacturer could determine how the article would be used. The petition further cites court cases to demonstrate that courts have upheld this definition of intended use and treated the legislative history as authoritative. The petition refers to a D.C. circuit court ruling that a claims-based understanding of intended use had been recognized “as a matter of statutory interpretation.”

The petition also addresses the FDA’s definition of intended use established in 1952, with particular reference to the requirement that if a drug manufacturer is aware a drug or device may be used for conditions other than the one for which it is offered, it must provide adequate labeling for such uses (the last sentence in the rule). This requirement, they say, has long been an issue and has been questioned by the courts. The petition cited a court ruling rejecting the FDA’s expanded definition of intended use. In that case, Association of American Physicians and Surgeons, Inc. v. FDA, the court determined the FDA can only regulate claimed uses of drugs rather than “all foreseeable or actual uses.”

Although the FDA proposed in 2015 to remove the last sentence of the intended use definition, the petitioners say it “dramatically shifted gears” in the final rule. Instead of deleting the final sentence, the FDA replaced it with a new sentence establishing an open-ended “totality of evidence” standard, stating that if the evidence indicates a manufacturer objectively intends for a drug to have off-label uses, it must provide adequate labeling that accords with such intended uses.

The FDA argues the addition of the standard is merely a clarification of law to indicate that knowledge of an actual use didn’t automatically trigger adequate labeling obligations. The petition alleges, however, that the final rule adopts a new standard not supported in existing law, and that represents a significant change with constitutional and public health consequences. The petitioners cite case law to support their position that the totality of evidence approach has no standing in law. In particular, the petition cites the United States v. Article of 216 Cartoned Bottle (“Sudden Change”) case in which the court said, “[T]he intended use of a product may be determined from its label, accompanying labeling, promotional material, advertising and any other relevant source.”

The petition also cites recent lawsuits by drug and device makers alleging the FDA’s intended use regulations have a chilling effect on speech to minimize the risk and ameliorate the quality of care related to off-label uses. These cases, the petition states, highlight the First Amendment challenges raised by the traditional claims-based interpretation of intended use. The new standard “all but guarantees significant constitutional harms will result,” the petitioners write. They say it would not only risk the restriction of truthful and non-misleading promotional speech but also raise Fifth Amendment challenges because no one will know in advance what evidence may be considered sufficient to deem an actual use an intended use.