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FDA Proposes to Revise “Intended Use” Regulations (Again) to Clarify that Knowledge Alone Is Not Sufficient to Establish Intent

Last week FDA published a proposed rule that would revise the agency’s “intended use” regulations to clarify that a manufacturer’s knowledge of off-label use of its drug or device is, by itself, not sufficient to establish a violation of the Food, Drug, and Cosmetic Act (FDCA).

View Proposed Rule.

Why Intended Use Matters

“Intended use” is perhaps one of the most important concepts in FDA law. It is significant in two ways. First, a product’s intended use can dictate whether it is even subject to regulation by FDA, and if so, which regulatory requirements apply. Second, the “intended use” of the product must be consistent with the FDA-approved use(s) of that product. As we’ve noted previously, if a manufacturer promotes an FDA-approved drug for a use that has not been approved by FDA—i.e., the manufacturer engages in off-label promotion — FDA may view the promotion as evidence of a new, unapproved intended use and a violation of the FDCA.

How Does FDA Determine a Product’s Intended Use?

FDA’s regulations define intended use as the “objective intent of the persons legally responsible for the labeling” of a drug or device and outline the types of evidence that FDA considers when evaluating an individual’s or entity’s objective intent. In short, FDA’s regulations provide that the Agency may rely on any relevant source of evidence, including: express and implied claims made in product labeling or advertising, oral and written statements made by a manufacturer and its representatives, the circumstances surrounding a product’s distribution and the context in which it is sold, and—most relevant to this proposed rule—whether the manufacturer knows how its drug or device is actually being used by healthcare providers and consumers. This knowledge component is codified in the final sentence of FDA’s intended use regulations:

…if a manufacturer knows, or has knowledge of facts that would give him notice, that a drug [or device] …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.

Although FDA has repeatedly maintained that the Agency does not consider knowledge alone to be sufficient to demonstrate a product’s intended use, this sentence has led to concern that mere knowledge of off-label use could put a manufacturer at risk of FDA enforcement.

The Tortured History of FDA’s Intended Use Rulemaking: A Brief Summary

In 2015 FDA issued a proposed rule that, among other things, would have deleted the controversial “knowledge” sentence in order to address industry concerns and to “conform [the intended use regulations] to the Agency’s current practice in applying [them].” But when FDA published the final rule in 2017, the Agency did not delete the sentence; instead FDA revised the language, explaining that the Agency would evaluate the “totality of the evidence” when determining a manufacturer’s “objective intent.” In response to industry comments and a petition objecting to the 2017 final rule on both substantive and procedural grounds, FDA ultimately decided to delay the rule’s effective date indefinitely.

Changes Being Proposed (With Examples!)

In this new rule, FDA is proposing to amend its intended use regulations for drugs and devices (codified in 21 CFR § 201.128 and 21 CFR § 801.4, respectively) by (1) deleting the controversial “knowledge” sentence, (2) repealing the “totality of the circumstances” standard from the 2017 final rule, and, most notably, (3) adding a new clause (shown below in bold) to clarify that a manufacturer’s knowledge of off-label use is, by itself, not determinative of a new intended use:

Objective intent may be shown, for example, by circumstances in which the article is with the knowledge of such persons or their representatives, offered or used for a purpose for which it is neither labeled nor advertised; provided, however, that a firm would not be regarded as intending an unapproved new use for an [approved drug or cleared device] based solely on that firm’s knowledge that such [drug or device] was being prescribed or used by health care providers for such use.

Perhaps equally as notable is the fact that, in the preamble of the proposed rule, FDA describes a number of fact patterns to illustrate the Agency’s approach to evaluating intended use. For example, FDA explains that the following could be relevant to determining a product’s intended use:

  • Express claims and representations made by a company or its representatives
     
  • Claims or statements that imply that a product is intended for a particular use, for example:
    • “Suggestive product names such as Chronix, Shroomz, or e-Cialis” 
    • “Representations that the product contains a particular ingredient to imply a physiological effect, such as the inclusion of ‘aspirin’ or ‘sildenafil’ in the ingredient list”
       
  • A product’s characteristics or design, for example:
    • “The known physiological effects (medical or recreational) of a product that is unapproved for any medical use…” such as “dried herbs treated with synthetic tetrahydrocannabinol (THC)” [the active pharmaceutical ingredient in an FDA-approved drug]
    • “The product’s design or technical features,” such as “a device that includes software with a diagnostic function when the purported use does not include diagnosis”
       
  • The circumstances surrounding the distribution of a product and the context in which it is sold, for example:
    • “…a [manufacturer’s] repeated proactive detailing and delivery of large amounts of complimentary product samples to a health care provider whose patient population does not fall within the product’s approved population”
    • “Using personal, not business, emails and addresses for communications and deliveries.”

The Agency also provided numerous examples of evidence that, standing alone or in combination with an acknowledged FDA “safe harbor,” would not be determinative of intended use. (See 85 Fed. Reg. at 59725-26 for the specific examples provided.)

Take-Aways

If finalized, the proposed changes are unlikely to signal any meaningful change in FDA’s enforcement policy. As noted above, FDA has repeatedly said that it does not consider mere knowledge of off-label use to be determinative of a product’s intended use. Nonetheless, the issuance of this proposed rule is a notable development because of the importance of “intended use” in FDA’s regulation of drugs and devices. One also has to wonder if FDA’s proposed changes could have any bearing on allegations made or evidence offered (such as sales forecasts based on off-label use) in False Claims Act cases involving off-label promotion.

FDA is accepting comments on the proposed rule until October 23, 2020.

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