FDA Delays Intended Use Rule, Seeks Public Comment

Posted March 23, 2017

In response to strong criticism from industry, the Food and Drug Administration (FDA) has pushed the effective date for a new rule intended to clarify when tobacco products are regulated as medical products until March 2018—opening the door to possible changes. This decision comes weeks after three biopharmaceutical industry groups submitted a petition that accused the agency of violating its own rulemaking procedures and questioned how the rule would change the way the FDA assesses the intended use of drugs and medical devices.

The concept of “intended use” is significant from a regulatory standpoint because it highlights the fact that how a product is actually used once on the market may be different from what the manufacturer had originally intended. And what the manufacturer knows about the actual use of the product could have repercussions for marketing, labeling, and regulation in general.

The FDA defines intended use in the Code of Federal Regulations, Title 21, Sections 201.128 and 801.4. Based on this definition, the FDA is not only able to regulate products based on the intended uses expressed in product labeling, promotional claims, or advertising, but also on their actual uses, which depend on whether 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."

In the proposed version of the rule released in 2015, the FDA recommended deleting this statement, which is often referred to as the “knowledge” clause. Industry has long been concerned that this provision could lead the FDA to require new marketing applications based on a company's knowledge of a product's off-label use.

However, in the final rule released this past January, the agency stated that based on feedback it had received, it believed its “clarification goals” could be better achieved by rewording the statement as opposed to deleting the language in question.

The amended statement read: "And if the totality of the evidence establishes that a manufacturer objectively intends that a drug introduced into interstate commerce by him is to be used for conditions, purposes, or uses other than ones for which it is approved (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 drug from the requirements of section 502(f)(1), to provide for such drug adequate labeling that accords with such other intended uses."

It was the addition of the phrase “totality of the evidence” that struck a chord with industry groups.

In a petition filed in February by the law firms Sidley Austin LLP and Ropes & Grey, the Medical Information Working Group, the Pharmaceutical Research and Manufacturers of America, and the Biotechnology Organization groups contended that the final rule runs contrary to “the settled interpretation” of intended use and puts “unconstitutional restraint on protected speech regarding unapproved uses of approved medical products.”

Because of the questions and concerns raised in the petition, the FDA said it decided to push the effective date for the rule from March 21, 2017 to March 19, 2018 to “invite public comment on the important substantive issues raised by the petition and to allow additional time to fully evaluate these issues and any other issues raised in response to this request for comments.”

Still, the FDA defended its proposed changes, saying they were an attempt to make the intended use policy clearer. The changes were meant “to clarify that FDA would not regard a firm as intending an unapproved new use for an approved or cleared drug or device based solely on that firm's knowledge that its product was being prescribed or used by doctors for such use,” the agency wrote in a Federal Register notice published earlier this week.

In the notice, the FDA upheld its “longstanding position” of looking at any “relevant source of evidence,” which could include product labeling, promotional claims and advertising, oral or written statements made by the manufacturer or one of its representatives, and circumstances surrounding the distribution or sale of a product.

The amendments “were not intended to reflect a change in FDA's approach regarding evidence of intended use for drugs and devices,” the agency wrote.

In the petition, industry groups also argued that the FDA did not follow proper rulemaking procedures―violating the fair notice requirement under the Administrative Procedure Act―and asked that the agency stay the rule indefinitely.

Medical device trade association AdvaMed supported the call for the FDA to ditch the language included in the final rule.

“Along with many other stakeholders, we believe the final rule should be disregarded as provisions added late in the process to the final rule are expansive, unwarranted, and raise interpretational issues,” Khatereh Calleja, AdvaMed’s senior vice president for technology and regulatory affairs, told Bloomberg BNA. “Specifically, the totality standard set out in the final rule is inconsistent with the long recognized definition of intended use and creates substantial uncertainty for manufacturers.”

Comments can be submitted through www.regulations.gov until May 19.