Confusion and concerns over portions of a tobacco-related final rule have pushed the US Food and Drug Administration (FDA) to delay indefinitely the implementation of the sections dealing with the types of evidence FDA may consider to determine how a manufacturer intends for its medical product to be used.

"This is a determination that can have significant implications for, among other things, how manufacturers communicate about and promote their products. How we determine intended use is an important issue that touches many fundamental aspects of the FDA’s work," FDA Commissioner Scott Gottlieb said in a statement in January.

FDA had sought comments on the proposal to delay the 19 March 2018 effective date of the portion of the rule related to intended use of medical products, though the tobacco-related portions of the final rule will go into effect.

"This final rule delays the effective date of the amendments to allow further consideration of the substantive issues raised in the comments received regarding the amendments," FDA said in a Federal Register notice published Thursday.

"We believe that the delay is reasonable and appropriate in light of the complex issues under consideration and the wide range of concerns, proposals, and recommendations we have received in comments from stakeholders on these issues," FDA said.

The agency also noted in a previous Federal Register notice that issues raised in a petition filed by PhRMA, BIO and the Medical Information Working Group, as well as the comments on the 2015 proposed rule and others from 2017 "underscore for FDA the potential for confusion related to the language in the final rule."

Patti Zettler, associate professor of law at Georgia State University School of Law, told Focus in January: "As a preliminary matter, I think the indefinite delay of this rule suggests that there is an improved prospect that FDA will not go forward with the rule as is. In the meantime, though, some of the language that industry has long been concerned about - that knowledge of unapproved uses can be evidence of intended use - remains in place."

Background

At issue is how the initially proposed rule sought to remove a sentence, which FDA Law Blog last February called "the famous 'knowledge' sentence: 'But if a manufacturer knows, or has knowledge of facts that would give him notice, that a [drug or device] introduced into interstate commerce . . . is to be used for conditions, purposes, or uses other than the ones for which he offers it, he is required to provide adequate labeling for such a drug/device which accords with such other uses to which the article is to be put.'"

But the final rule did not remove the sentence and instead amended it with new language that angered industry groups, which called the move "a new and unsupported legal standard."

The new sentence said: "And if the totality of the evidence establishes that a manufacturer objectively intends that a device [or drug] introduced into interstate commerce by him is to be used for conditions, purposes, or uses other than ones for which it has been approved, cleared, granted marketing authorization, or is exempt from premarket notification requirements (if any), he is required, in accordance with section 502(f) of the Federal Food, Drug, and Cosmetic Act, or, as applicable, duly promulgated regulations exempting the device from the requirements of section 502(f)(1), to provide for such device [or drug] adequate labeling that accords with such other intended uses."

Moving Forward

As far as whether FDA might take another stab at what it means by intended use with a different or further amended rulemaking, Zettler noted that that largely depends on how high a priority it is for the agency.

FDA also explained how several comments raised legal concerns with the final rule, including arguments to the effect that the rule violates the First Amendment by regulating truthful speech regarding lawful activity.

Zettler added: "It's important to distinguish the agency's use of knowledge, or a 'totality of the evidence,' to determine the intended use of wholly unapproved products and its use of such evidence to determine the intended use of approved products. I think the First Amendment arguments are stronger when considering approved products, and the connection to off-label promotion, which is where courts have seemed inclined to question the constitutionality of FDA's policies."