Here are a couple of non-litigation related matters that we thought our readers need to know about. First, the FDA. We’ve pointed out before that the FDA’s “intended use” regulations for drugs (21 C.F.R. §201.128) and devices 21 C.F.R. §804.1) both contain the following potentially disturbing language: [I]f a manufacturer knows, or has knowledge of facts that would give him notice that a device introduced into interstate commerce by him 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 device which accords with such other uses to which the article is to be put. This language has the potential, if the FDA wanted to, to allow the prosecution of a drug or device manufacturer for an “adulterated”/”misbranded” product (for not having “adequate labeling”), merely because that manufacturer KNEW ABOUT off-label use of its products – forget promotion (truthful or otherwise).

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 DEPTHOn 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.

Whether a company will be deemed to have misbranded a product by promoting it for off-label use in violation of the FDCA may depend on whether the use is inconsistent with the FDA-approved labeling and whether it qualifies as an “intended use” by the company, as set forth by the “intended use” regulations. See 21 C.F.R. §§ 801.4 (devices) and 201.128 (drugs).The FDA first proposed amended regulations on “intended use” in 2015 followed by a new final regulation in 2017.

Importantly, Commissioner Hahn also noted that the proposed rule is also intended to “clarify an important point: that a firm’s knowledge that a health care provider has prescribed or used an approved or cleared medical product for an unapproved use, standing alone, is not sufficient to establish the products intended use.” Included in the actions intended to accomplish this, the proposed rule specifically:deletes the last sentence from the intended use regulations for both drugs (21 C.F.R. § 201.128) and devices (21 C.F.R. § 801.4);inserts a new clause in the intended use regulations for both drugs (21 C.F.R. § 201.128) and devices (21 C.F.R. § 801.4) stating: “provided, however, that a firm would not be regarded as intending an unapproved new use for an [approved drug / approved or cleared device] based solely on that firm’s knowledge that such [drug / device] was being prescribed or used by health care providers for such use.”; andadds language to the intended use regulation for both drugs and devices to include “the design or composition of the article” as possible evidence of the responsible party’s intended use of the article.

In reaching that conclusion, OLC interpreted “intended use” — a foundational doctrine in food and drug law — to include a product seller’s knowledge of actual use and the “circumstances surrounding distribution” of the product. The OLC opinion thus departs from FDA’s 2015 proposed rule interpreting “intended use” under 21 C.F.R. §§ 201.128 and 801.4. Because OLC opinions are binding on agencies such as FDA, the opinion raises questions regarding the scope of regulated firms’ liability under the misbranding and new drug/device approval provisions of the FDCA.In 2015, FDA proposed to revise the existing regulatory definitions of “intended use” at 21 C.F.R. §§ 201.128 and 801.4 by eliminating the knowledge prong of the definitions.

Proposed revisions to the intended use regulationsThe intended use of a product, as interpreted by FDA under the regulations in 21 C.F.R. §§ 801.4 (covering devices) and 201.128 (covering drugs), determines whether that product meets the statutory definition of a device or a drug, or whether it is being marketed for a use that exceeds its existing clearance or approval. FDA says the proposed rule aims to eliminate longstanding confusion created by the view that the last sentences of 21 CFR §§ 201.128 and 801.4 indicate that a manufacturer’s mere knowledge of an unapproved use of its approved product automatically triggers a requirement for updated labeling. The proposed rule clarifies that while knowledge is one element FDA may consider in determining a product’s intended use, this knowledge alone on the part of a manufacturer does not render illegal the distribution of that approved product based on current labeling.

Modifications and Effects of the Proposed Rule and Its PreambleIn FDA’s press announcement regarding the proposed rule, the agency emphasized that, like the 2015 proposed rule and 2017 final rule, today’s proposed “intended use” rule does not reflect a change in FDA’s policies and practices but rather is intended to “clarify the regulatory language describing the types of evidence [the agency] considers relevant to determining a product’s intended use.” In particular, by revising 21 C.F.R. §§ 201.128 and 801.4, the proposed rule is intended to “clarify an important point” and indeed, the most serious concern raised by industry, “that a firm’s knowledge that a health care provider has prescribed or used an approved or cleared medical product for an unapproved use, standing alone, is not sufficient to establish the product’s intended use.” Significantly, however, FDA is not actually giving up new ground here.

Comments must be submitted by April 19, 2017. Final Rule on Definition of “Intended Uses” On January 9, 2017, FDA published a 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” which amends the definition of “intended use” for purposes of drugs (21 C.F.R. § 201.128) and devices (§ 801.4).28 The actual revisions to the regulatory text do not reflect a change in FDA policy; instead, FDA is updating the regulations to reflect how it currently applies its policies.29 Although the bulk of the Final Rule focuses on products derived from tobacco, FDA makes clear that these changes apply to all drugs and devices.

Changes to Drug & Device Intended Use DefinitionsWhen the proposed rule was published on September 25, 2015, it appeared that FDA was attempting to slip in a major regulatory change to the “intended use” definition applicable to drugs and devices without explanation. FDA proposed deleting the following language from 21 C.F.R. §§ 201.128, 801.4: “But if a manufacturer knows, or has knowledge of facts that would give him notice, that a drug introduced into interstate commerce by him 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 which accords with such other uses to which the article is to be put.” The only explanation offered was that the “clarifying change” would “conform them regulations to how the Agency currently applies the regulations.”

There can be lots of talk about what FDA’s policy is on what a manufacturer can and cannot say about unapproved uses for its drug or device. Discussions about changing 21 C.F.R. § 201.128 (drugs) & 801.4 (devices) have dragged on for a while, even with the Amarin settlementand with other FDA statements suggesting that the regs do not reflect current policy. FDA policy, of course, involves more than just a few sentences in a regulation or guidance document.