The U.S. Food and Drug Administration (FDA) will not narrow the scope of evidence the agency considers relevant when defining a drug or medical device’s “intended use.”

The newly implemented final rule, which took effect Sept. 1, reaffirms the FDA’s wide latitude of discretion in establishing an off-label use case against pharmaceutical and medical device companies. It describes what evidence the agency will consider relevant to determine a drug or medical device’s intended use under the Food, Drug, and Cosmetic Act.

The regulation brings to an end a rulemaking process that began in 2015, when the FDA first proposed amending existing directives.

The first iteration of a final intended use rule was published in January 2017, but a controversial “totality of evidence” standard the FDA snuck in sparked so much opposition from industry that the agency decided, in response to a petition, to stay the rule indefinitely. That standard would have allowed the FDA “to consider any evidence, including knowledge,” the petition stated, that would have then triggered drugmakers to have to provide “adequate labeling” in accordance with all intended uses.

In the new rule, which repealed portions of the 2017 proposal, the FDA states “a firm would not be regarded as intending an unapproved new use … based solely on that firm’s knowledge that such drug or device was being prescribed or used by health care providers for such use.” However, the FDA maintains its authority to rely on “any relevant source of evidence” to establish intended use.

“Because the final rule largely codifies the FDA’s current approach, to which the courts typically defer, it is not likely to result in major changes from an enforcement standpoint. Nevertheless, by bringing some closure to the longstanding debate, it does provide potentially a clearer basis for both preparing and contesting enforcement actions.”

Suzanne Levy Friedman, Senior Associate, Hogan Lovells

The agency made clear knowledge of an off-label use in consideration with other evidence might still help prove intended use. “While manufacturer knowledge is not enough on its own to trigger the requirement to update labeling, it is still a relevant factor,” says Suzanne Levy Friedman, a senior associate at law firm Hogan Lovells.

“Depending on the context, manufacturer knowledge of an off-label use could be considered akin to an implied claim, because knowing about pervasive unapproved use of one’s own drug or device and doing nothing about it can be understood as tacit endorsement of that use,” Friedman adds. “While implied claims are harder to police … when they are significant or frequent enough, they are also hard to disavow.”

Such claims can arise nonverbally as well—such as through a product’s inherent characteristics, circumstances surrounding its distribution, and in some cases knowledge—and are, therefore, “critical to incorporate into company promotional trainings and policies,” she says.

The FDA broadly defines intended use as the “objective intent of the persons legally responsible for the labeling of [the drug or medical device].” Objective intent covers a wide array of activities and speech that includes, for example, “labeling claims, advertising matter, or oral or written statements by such persons or their representatives,” according to the final rule. The FDA explicitly objected to comments that such an assessment should rely primarily or only on promotional claims.

While many in the life sciences industry had hoped the FDA would interpret intended use more narrowly than it had in the past, the agency indicated nothing about its stance has changed. “The FDA is going to continue to use any and all evidence it can possibly gather about potential off-label use in trying to determine if a manufacturer is objectively engaging in off-label marketing and distribution,” says Kevin Madagan, a partner at law firm Reed Smith.

In disagreeing with industry comments, the FDA’s regulation for the first time expressly states the “design or composition” of a medical device “reflects FDA’s longstanding and current policy that these are relevant to intended use.” An example of this may include “the design of a stent to be specifically sized for a use that is different from the purported use,” the agency stated in a preamble to its rule.

The regulation does not disturb FDA current policies concerning “scientific exchange” and other so-called “safe harbors” in which truthful, non-misleading statements will not be used as evidence to establish a new intended use.

“This is significant insofar as it reinforces the rule basically preserves the status quo,” says William McConagha, a partner in the life sciences and healthcare practice at Skadden. “In this respect, the new rule basically just repurposes the FDA’s old playbook on intended use.”

Compliance message

Chief compliance officers and in-house counsel in the life sciences industry should take note of the FDA’s intended use regulation, since off-label use can, and often does, result in criminal prosecutions and massive penalties under the False Claims Act.

“Because the final rule largely codifies the FDA’s current approach, to which the courts typically defer, it is not likely to result in major changes from an enforcement standpoint,” Friedman says. “Nevertheless, by bringing some closure to the longstanding debate, it does provide potentially a clearer basis for both preparing and contesting enforcement actions.”

Compliance practitioners might find especially helpful the examples the FDA has provided illustrating scenarios that would not trigger regulatory action. One instance cited: “During an internal meeting, a firm’s CEO displays a slide of internal sales projections for its approved product. The slide reflects potential sales for an unapproved use that is widely recognized as the standard of care.”

Another scenario is where “a firm makes corporate filings or submissions to the U.S. Securities and Exchange Commission that include required disclosures of development activities or potential or actual sales for an unapproved use,” the FDA stated.

The agency also emphasized First Amendment considerations do not curtail its authority to consider a broad range of potential evidence in policing industry activities, “which might be noted in future cases brought by the Department of Justice,” Friedman says. She recommends companies “continue to be vigilant about how your products are being marketed and, particularly, how your personnel, representatives, and contractors—including influencers—promote them.”

Notwithstanding a series of court decisions in recent years addressing First Amendment protections as they apply to commercial speech, “many companies have remained cautious about whether and how to change their approach to promotional activity, which we believe is wise,” McConagha says. While the First Amendment protects truthful, non-misleading speech, “promotion of unapproved uses can still invite enforcement risk if it is in any way false or misleading.”

“Companies should continue working through the labeling and advertising review committees they have always used,” McConagha adds. “They should continue to train sales reps about the FDA-approved indication for their product and the details of the approved package insert or instructions for use. It is also important for companies to ensure their employees who are conducting review of materials and promotional activities are well-versed about the guidance the FDA has provided and they stay abreast of recent enforcement activity, which can provide a helpful understanding of the government’s priorities and perspectives.”