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September 29, 2020

FDA Issues Proposed Rule to Amend Intended Use Regulations


On September 23, 2020, the US Food and Drug Administration (FDA) released a proposed rule that would amend its regulations governing the types of evidence relevant to determining the "intended use" of a drug or device under the Federal Food, Drug, and Cosmetic Act, the Public Health Service Act, and FDA's implementing regulations.1 This proposed rule would also repeal and replace portions of FDA's January 9, 2017 final rule addressing the same issues,2 which were never put into effect. FDA proposes that any final rule would take effect 30 days after the date of publication of the final rule in the Federal Register. Comments to the proposed rule are due on October 23, 2020.

The proposed rule would amend 21 C.F.R. §§ 201.128 and 801.4, relating to the intended uses of drugs and medical devices, respectively. In the preamble to the proposed rule, FDA notes that it is amending its regulations to "better reflect the Agency's current practices" with respect to evidence of intended use,3 and to clarify that a firm's knowledge of an unapproved use of an approved drug or device is not, on its own, sufficient evidence to establish a new intended use. Additionally, FDA proposes to add to these sections a reference to 21 C.F.R. § 1100.5 ("Exclusion from tobacco regulation") to define when a product made or derived from tobacco will be regulated as a drug, device, or combination product.

Evidence Relevant to a Product's Intended Uses

The prior rule issued by FDA in 2017 created significant confusion, in part due to its broad language. In the preamble to the new proposal, FDA referenced its "longstanding position [] that, in evaluating a product's intended use, any relevant source of evidence may be considered," including labeling, promotional claims, and advertising.4 FDA also makes clear that, when establishing intended use, it will not look solely at a firm's "subjective claims of intent" about the use of a product, but also at "direct and circumstantial objective evidence" of the intended use of a product.5 FDA further notes that such objective evidence is of particular importance when it "contradicts the firm's claims."6 Notably, however, FDA's proposed rule does not explicitly reiterate the "totality of the evidence" standard for ascertaining a manufacturer's objective intent that was set out in the 2017 intended use regulation.7 FDA further explains that the proposed rule will "clarify the types of evidence relevant to determining a product's intended uses," and distinguish between these types of evidence, and types of evidence that, "standing alone, are not determinative of intended use."8 FDA sets forth examples of both types of evidence, but cautions that these examples are "for illustrative purposes only" and are not "comprehensive or restrictive."9

Agency Examples of Evidence Relevant to Establishing Intended Use

FDA provides in the preamble to the proposed rule examples of the types of evidence "relevant to establishing intended use,"10 including:

(1) Express Claims: a firm's explicit claims about the use of a product, such as claims made in the labeling or advertising for a product;

(2) Implied Claims: a firm's claims about the intended use of a product that can be implied from, for example, suggestive product names or representations that a product contains an ingredient known to produce a particular physiological effect;

(3) Product Characteristics and Design: evidence including the known physiological effects or uses of a product ("medical or recreational") that are "unapproved for any medical use," and the design or technical features of a product; or

(4) Circumstances of the Sale or Distribution: including evidence of the population to whom a firm is proactively detailing a product, a firm's distribution of large numbers of samples to healthcare providers with patient populations outside of the approved population for the product, and "[c]ircumstances and context surrounding the sale."11

FDA proposes to consider evidence of product's intended use on a case-by-case basis, considering the "individual and unique circumstances of each case."12 In some cases, FDA contends that a "single piece of evidence" may be sufficient to establish the intended use of a product, while in other cases FDA observes that a determination regarding the intended use of a product may be based on multiple pieces of information.13

Agency Examples of Evidence That, On Its Own, Is Not Determinative of Intended Use

FDA also offers examples of evidence that would not, on its own, establish intended use. These include evidence of a firm's knowledge that a healthcare provider is prescribing a drug or device for an unapproved use (discussed further below), dissemination of safety information about an unapproved use to providers to mitigate risk of such use to patients, and references to sales for an unapproved use in a filing with the U.S. Securities and Exchange Commission.14

Evidence of Knowledge of Unapproved Uses of Drugs or Devices

FDA's proposal would amend 21 C.F.R. § 201.128 to remove the final sentence ("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.") and add to this section a provision confirming that "a firm would not be regarded as intending an unapproved new use for an approved drug based solely on that firm's knowledge that such drug was being prescribed or used by health care providers for such use."15 FDA proposes to make comparable changes to 21 C.F.R. § 801.4 regarding devices.

FDA explains that these revisions are aimed at addressing concerns expressed by firms that the unrevised regulations could have been read to mean that, when a firm becomes aware of a drug or device being prescribed or used for an unapproved use, the firm is required to alter the label to provide directions for this use and to cease selling the drug until a supplemental new drug application reflecting the new use is approved by FDA.16 As noted above, FDA's position as explained in the proposed rule is that a firm's knowledge of an unapproved use is not sufficient on its own to establish an intended use. However, FDA will consider such knowledge in the context of all other relevant evidence to determine whether there is "sufficient evidence to establish a new intended use."17

First Amendment Concerns

FDA acknowledges potential First Amendment concerns with the Agency's approach to establishing the intended use of a product, noting that commenters to the earlier iteration of this rulemaking had raised such concerns. Although FDA explains that these proposed amendments to the intended use regulations "are not intended to address specific concerns" under the First Amendment,18 FDA spends considerable time explaining why, in its view, the proposed rule is consistent with the First Amendment. First, FDA states that the rule is "limited in scope," describing the types of evidence that FDA may consider when making an intended use determination without identifying types of evidence that will always be determinative of a product's use.19 Second, FDA notes that the proposed rule, if finalized, would not impact statutory exclusions from the definitions of "drug" or "device," such as the exclusion of structure/function claims contained in dietary supplement labels and health claims contained in the labels of conventional foods or dietary supplements.20 Third, FDA takes the position that the proposed revisions "do not reflect a change in FDA's policies and practices," regarding the types of communications that may, on their own, establish intended use.21

FDA also asserts that courts have held that FDA's reliance on "speech as evidence of intended use" is permissible under the First Amendment, quoting from court decisions stating that "th[e] use of speech to infer intent, which in turn renders an otherwise permissible act unlawful, is constitutionally valid" and it is "constitutionally permissible for the FDA to use speech [by the manufacturer]" to infer intended use.22 We note in this regard that the cases referenced by FDA predate the Supreme Court's recent decision in Barr v. American Association of Political Consultants, Inc., in which the Supreme Court invalidated a provision of the Telephone Consumer Protection Act that exempted government debt-collection calls from a ban on robocalls to cell phones.23 In the decision, five justices held that the exemption violated the First Amendment because it was content-based and failed strict scrutiny, rejecting the other four justices' view that the exemption was a commercial regulation subject only to intermediate scrutiny under Central Hudson. Subsequently, in September 2020, the Sixth Circuit in International Outdoor, Inc. v. City of Troy, Michigan, interpreted American Association of Political Consultants, in combination with Sorrell v. IMS Health, Inc. and Reed v. Town of Gilbert, to require that all content-based speech restrictions be reviewed under the strict scrutiny standard, even when they concern commercial speech.24

The FDA also argues in the preamble to the proposed rule that, despite the Second Circuit decision in United States v. Caronia providing that manufacturers cannot be criminally prosecuted for speech promoting lawful, off-label uses for FDA-approved drugs, FDA may still consider promotional speech as evidence in an enforcement action brought under a misbranding theory.25 Finally, FDA argues that this approach to determining intended use is "appropriately tailored to achieve substantial public health interests," as speech is only one type of evidence relevant to an intended use analysis.26

Unlike in the preamble to the January 2017 final rule that FDA now proposes to replace, the preamble to this proposed rule does not address whether FDA views this proposal as consistent with the Southern District of New York's decision in Amarin Pharma v. FDA.27 In the preamble to the January 2017 final rule, FDA acknowledged the holding in Amarin that, under Caronia, an enforcement action for misbranding cannot be based solely on truthful and non-misleading speech promoting an off-label use of an FDA-approved product, but determined that a subsequent Second Circuit case (United States ex rel. Polansky v. Pfizer, Inc.) left the door open for FDA to consider promotional speech as "evidence that a drug is intended for a use that is not included on the drug's FDA approved label."28 In the preamble to this proposed rule, FDA does not address the Amarin decision, instead relying exclusively on the Second Circuit's decision in Polansky to support its argument that it may continue to rely on promotional speech as evidence of intended use.

Key Takeaways for the Pharmaceutical and Medical Technology Industries

The proposed rule appears to be an attempt to address some of the ambiguity in 21 C.F.R. § 201.128 and to make clear, perhaps in the face of clear constitutional limitations, that mere knowledge of an unapproved/uncleared customer use of a product is insufficient to establish the manufacturer's intended use.29 The examples FDA gives are unlikely to be surprising or new to those who follow these issues. However, importantly, the concept that a "single piece of evidence" could establish intended use, along with FDA's continued reliance on "circumstances surrounding sale or distribution" still would leave FDA and the DOJ with considerable enforcement discretion.

The proposed rule outlines FDA's longstanding position that, while "promotion" is undefined in statute or regulations, FDA will consider "any claim or statement made by or on behalf of a firm that explicitly represents a product for a particular use" to constitute evidence of an intended use, and thus, promotion that is subject to the promotional labeling regulations (e.g., fair balance, indication statement, etc.). The proposed rule's examples also confirm FDA's position that evidence of intended use could apply for both external as well as internal materials (e.g., FDA's reference to internal "sales and distribution metrics" and whether a "firm does not give any direction to sales or marketing staff . . ."). 

The proposed rule also provides an example of social media that, if finalized, may be instructive for industry given the limited FDA guidance for social media. Specifically, FDA proposed that it would evaluate a manufacturer "following" a non-profit patient group's social media account as potentially evidence of a firm's intended use.30 Under FDA's example, the non-profit patient group is for a rare disease with no FDA-approved treatment, but the firm is investigating a potential option. FDA proposed that it would not consider the firm's act of "following" the non-profit alone as evidence of intended use, provided that the "firm [social media] account does not make any comments or otherwise endorse any specific posts on the non-profit account." This position, if finalized, is consistent with FDA's prior positions on social media, in which the agency has issued enforcement letters for firms that have "liked" or "shared" posts that were non-compliant with applicable promotional regulations.

The provision's vagueness also remains troubling, given the fact that the misbranding statute provides for strict misdemeanor criminal liability. While stakeholders are likely to comment on the proposal, and a robust public discourse about these issues is likely to ensue, industry should continue to closely follow FDA's Consistent with FDA-Approved Labeling (CFL) Guidance both with regard to core commercial strategy documents, such as descriptions of customer targeting, investment in certain sales tactics or distribution arrangements, and, of course, sales and marketing materials disseminated to healthcare providers and other customers. If the proposed rule becomes final, it will further emphasize the need for the medical products industry to be strategic about how it drafts product labeling and marketing materials.

Given the central role of intended use under the Federal Food, Drug, and Cosmetic Act, the proposed rule is important in that, once finalized, the regulation could guide agency enforcement and regulatory decision making for many years to come. Stakeholders should consider submitting comments in order to ensure FDA's thinking on intended use is consistent with the reality of product planning, communications, and use, as well as constitutional constraints.

© Arnold & Porter Kaye Scholer LLP 2020 All Rights Reserved. This Advisory is intended to be a general summary of the law and does not constitute legal advice. You should consult with counsel to determine applicable legal requirements in a specific fact situation.

  1. Regulations Regarding "Intended Uses," 85 Fed. Reg. 59,718 (Sept. 23, 2020).

  2. 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. 2,193 (Jan. 9, 2017).

  3. 85 Fed. Reg. at 59,720.

  4. 85 Fed. Reg. at 59,721.

  5. 85 Fed. Reg. at 59,721.

  6. 85 Fed. Reg. at 59,721-22.

  7. 85 Fed. Reg. at 2,217.

  8. 85 Fed. Reg. at 59,724-25.

  9. 85 Fed. Reg. at 59,724, 59,725.

  10.  85 Fed. Reg. at 59,724.

  11. 85 Fed. Reg. at 59,724-25.

  12. 85 Fed. Reg. at 59,724.

  13. 85 Fed. Reg. at 59,724.

  14. 85 Fed. Reg. at 59,725-26.

  15. 85 Fed. Reg. at 59,729.

  16. 85 Fed. Reg. at 59,721.

  17. 85 Fed. Reg. at 59,722.

  18. 85 Fed. Reg. at 59,722.

  19. 85 Fed. Reg. at 59,723.

  20. 85 Fed. Reg. at 59,723, 59,723, n. 6.

  21. 85 Fed. Reg. at 59,723.

  22. 85 Fed. Reg. at 59,723 (citing Whitaker v. Thompson, 353 F.3d 947, 953 (D.C. Cir. 2004)).

  23. 140 S. Ct. 812 (2020).

  24. Nos. 19-1151/1399, 2020 WL 5269822 (6th Cir. Sept. 4, 2020).

  25. 85 Fed. Reg. at 59,723-24 (citing United States ex rel. Polansky v. Pfizer, Inc., 822 F.3d 613 n.2 (2d Cir. 2016)).

  26. 85 Fed. Reg. at 59,724.

  27. 119 F. Supp. 3d 196 (S.D.N.Y. 2015).

  28. 82 Fed. Reg. at 2,209.

  29. While the scope of evidence to establish intended uses still remains a live issue, cases such as Amarin Pharma, Inc. v. United States Food & Drug Admin., 119 F. Supp. 3d 196 (S.D.N.Y. 2015) and the most recent decision in United States v. Facteau, Crim. No. 1:15-cr-10076-ADB 2020 WL 5517573 (D. Mass. Sept. 14, 2020) showcase the stakes for regulated industry, should ambiguity in FDA's intended use regulations continue to exist.

  30. FDA's example appears to refer to a "firm's account" rather than a specific "branded" social media account, which may suggest that FDA could use evidence of a branded account "following" independent third-party accounts as evidence of intended use. However, if the branded account merely "followed", and did not "like", "share", or otherwise comment, it remains unclear if FDA would use the action of following alone as evidence of intended use.