On September 23, 2020, the US Food and Drug Administration (FDA) published its Regulations Regarding “Intended Uses” Proposed Rule to amend its “intended use” regulations at 21 C.F.R. §§ 201.128 and 801.4 and with the intent to clarify that how healthcare providers (HCPs) prescribe or use a product cannot be the sole basis for determining intended use. Comments on the Proposed Rule must be submitted to FDA by October 23, 2020.

IN DEPTH

On September 23, 2020, the US Food and Drug Administration (FDA) published its Regulations Regarding “Intended Uses” proposed rule (Proposed Rule) to amend its “intended use” regulations at 21 C.F.R. §§ 201.128 and 801.4. The Proposed Rule would amend FDA’s regulations regarding the types of evidence relevant to determining whether a product is intended for use as a drug or device under the Federal Food, Drug, and Cosmetic Act or Public Health Service Act and FDA’s implementing regulations for intended use. With the Proposed Rule, FDA intends to clarify that how healthcare providers (HCPs) prescribe or use a product cannot be the sole basis for determining intended use, a nod to the fact FDA does not regulate the practice of medicine and the fact that HCPs frequently use medical products off-label, or outside the manufacturer’s cleared or approved intended use, in their professional judgment.

Specifically, FDA proposes to:

• Delete the last sentence of 21 C.F.R. § 201.128 and 801.4, respectively, and to insert a new clause stating “provided, however, that a firm would not be regarded as intending an unapproved new use for an [approved or cleared medical product] based solely on that firm’s knowledge that such [product] was being prescribed or used by health care providers for such use.”

• Amend the text of these regulations to provide additional clarification regarding the types of evidence that the agency may deem relevant in determining a product’s intended use.

• Insert in these regulations a reference to 21 C.F.R. § 1100.5, which describes when a product made or derived from tobacco that is intended for human consumption will be regulated as a drug, device or combination product to clarify the interplay between the drug/biologic and device intended use regulations, respectively, and FDA’s tobacco product regulations.

In the preamble to the Proposed Rule, FDA included other examples of evidence that it does not consider to be determinative of intended use, standing alone:

• Limited instances where a firm disseminates safety information about unapproved uses to HCPs to minimize risks to patients

• A manufacturer’s official social media account “following” other social media accounts that relate to uncleared or unapproved indications, provided the manufacturer does not comment or endorse any specific posts on the other social media accounts

• Internal sales figures related to uncleared or unapproved uses

• Corporate filings or submissions to the Securities and Exchange Commission that include required disclosures of development activities or potential actual sales for uncleared or unapproved uses

• Summaries of aggregated clinical trial results provided to trial subjects to acknowledge their contributions, provided summaries are factual, balanced and complete presentations of trial results and do not make any conclusions about the safety or effectiveness of the uncleared or unapproved product or use and contain conspicuous and prominent statements that the product or use has not been cleared, approved or licensed by FDA.

However, the agency reaffirmed its longstanding position that the intended use of a product can be evaluated based on “any relevant source of evidence,” including direct and circumstantial evidence. This may include a product’s labeling, express or implied promotional claims, advertising and any other relevant evidence. This may include consumer intent if it is relevant to demonstrating the seller’s intent, training programs, financial arrangements, and other circumstances surrounding the manufacture, distribution, promotion or sale of a product. FDA provided a list of potentially relevant evidence in the preamble to the Proposed Rule, including:

• Express claims or representations

• Implied claims (including suggestive names and representations that the product contains a particular ingredient to imply a physiological effect)

• Product characteristics and design (including known physiological effects, known uses, and design or technical features)

• Circumstances of sale or distribution (circumstances and context surrounding the sale, and to whom and for whom the products are offered).

Rulemaking Background

The Proposed Rule, if finalized, would have the effect of repealing and replacing portions of FDA’s January 9, 2017 final rule (2017 Final Rule), “Clarification of When Products Made or Derived From Tobacco Are Regulated as Drugs, Devices, or Combination Products; Amendments to Regulations Regarding ‘Intended Uses’” (82 Fed. Reg. 2193, 2196 (Jan. 9, 2017), first proposed in 2015 (2015 Proposed Rule).

Whereas, in the 2015 Proposed Rule, FDA proposed to strike the last sentence of 21 C.F.R. §§ 201.128 and 801.4, respectively, in the 2017 Final Rule, FDA amendedthe last sentence of these respective regulations to clarify that the agency, absent “extraordinary circumstances,” would not consider a manufacturer as intending an uncleared or unapproved new use for a device based solely on the manufacturer’s knowledge that the product was being used or prescribed by doctors for such use. Rather, under the 2017 Final Rule, a manufacturer was not obligated to provide adequate labeling for that uncleared or unapproved use unless the totality of the evidence showed the manufacturer intended for its device to be used for that use.

However, the agency received an industry petition to stay and for reconsideration, which raised concerns that the amended language did not make clear that a manufacturer’s mere knowledge of an unapproved new use would not automatically trigger requirements for new labeling (that would, in turn, render distribution of that approved product unlawful without a new or supplemental marketing authorization). As a result, the agency delayed the 2017 Final Rule’s effective date and reopened the comment period to allow further consideration of the substantive issues raised in additional comments. As a result, with respect to the “intended use” definitions, the Proposed Rule essentially reflects a reversion to the 2015 Proposed Rule.

Comments on the Proposed Rule may be submitted to Docket FDA-2015-N-2002 by October 23, 2020.