Earlier this year, the United States Food and Drug Administration (FDA) published a proposed rule that would amend its “intended use” regulations for medical products and replace the 2017 Final Rule that never became effective.
The proposed rule tries to clarify confusion surrounding the last sentence in the current intended use regulations that some people read as requiring firms to provide adequate labeling for an unapproved use of their product if they have more knowledge that their product is being prescribed (or used) for such off-label use. Therefore, that reading of the wording may result in the distribution of many products being considered to be unlawful if not accompanied by a new approval or clearance.
The new proposed rule, therefore, attempts to resolve those challenges by eliminating the “totality of circumstances” language currently included in the last sentence in the regulation. The proposed rule also explicitly states that mere knowledge of an unapproved use is, by itself, insufficient for the FDA to find a new intended use by adding, “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.”
Even with the change, the preamble of the proposed rule makes clear that knowledge will still remain a factor in the FDA’s overall evaluation of objective intent as the FDA will look at “all relevant evidence” in making its determination of intended use. One factor of that would be a firm’s knowledge that health care providers are using or prescribing their product for unapproved or uncleared uses. Therefore, while the “totality of evidence” standard will be eliminated, the concept still remains in place.
Examples Provided in the Proposed Rule
The proposed rule also provides other examples of the types of “relevant evidence” the FDA will consider in its evaluation of a firm’s objective intent. In addition to express claims and representations in labeling, promotional material, and advertising, the FDA will also look at:
- Implied claims (such as product names or directions for use that suggest a different use or representations that a product contains a specific ingredient, implying a physiological effect);
- Product characteristics and design (such as inclusion of specific ingredients with known physiological effects in products that are not approved for medicinal use), the known use of a product that is unapproved for medical use, or the product’s technical features; and
- Circumstances of the sale or distribution, such as who the sales force is detailing or the context surrounding the sale.
FDA also gave several specific examples of evidence that, when standing alone, would not be dispositive of a new intended use. For example, in the case of a drug with an unapproved use that is broadly accepted in the medical community and the firm has submitted an efficacy supplement to add such new intended use. If the boxed warning and REMS materials already warn of the risks of such unapproved use in general terms but the firm disseminates additional specific safety and warning information to health care providers to minimize the risk to patients receiving the drug for unapproved use, the safety and warning information does not expressly or implicitly promote the efficacy of the unapproved use.
Conclusion
The proposed rule does not seem to make many big changes with respect to intended use, so it still is very important that companies establish clear policies regarding sales and promotional activities and include regulatory and/or legal review at each step of its product commercialization.
Additionally, while it is helpful that FDA provided a handful of examples in the proposed rule, those examples are very face specific and may be evaluated differently based on a small tweak in facts.
The comment period on the proposed rule recently closed, so it will be interesting to see what final rule, if any, the FDA puts forth.