On August 2, 2021, the U.S. Food and Drug Administration (“FDA”) published a final rule amending existing regulations (21 C.F.R. § 201.128 and 21 CFR § 801.4) that describe the types of evidence relevant to determine a drug or device’s intended use under the Food, Drug and Cosmetic Act (“FDCA”). See 86 Fed. Reg. 41,384–85.
This final rule, which takes effect as of September 1, 2021, withdraws and replaces a final rule that FDA promulgated on January 9, 2017, but which never became effective due to an outcry concerning a problematic knowledge provision that was contrary to the statutory scheme of the FDCA and to physicians’ autonomy to use FDA-approved products in an off-label manner.
Prior to the 2021 final rule, FDA issued a proposed rule on September 23, 2020 that eliminated the 2017 rule’s knowledge provision and was much more aligned with FDCA intent and current FDA policy and practice. FDA maintains, and we agree, that August 2021 final rule remains largely unchanged from the 2020 proposed language.
The following is a review of some important changes that FDA regulated entities should take note of as they develop and market FDA regulated products:
Mere Knowledge of an Off-Label Use Does Not Create New Labeling Obligations
But if a manufacturer knows, or has knowledge of facts that would give him notice that a [drug / 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 [drug / device] which accords with such other uses to which the article is to be put.
This language created confusion in the past, in particular because certain FDA regulated products are widely used for off-label purposes. If FDA included the above language in the final rule, it would mean that a drug or device manufacturer would be obligated to update its product’s labeling to include any off-label use that the manufacturer becomes aware of. The manufacturers would also be required to cease selling the product until a supplemental application with the new use was approved. By not including this language in the final rule, FDA clarifies that manufacturers do not have such an obligation simply because they are aware of off-label uses.
Knowledge of Off-Label Use Alone Does Not Create New Intended Uses
Further, FDA has included new language to clarify that knowledge of an off-label use alone does not create new intended use; however, such use – together with other evidence – could help prove an intended use:
[P]rovided, however, that a firm would not be regarded as intending an unapproved new use for a device approved, cleared, granted marketing authorization, or exempted from premarket notification based solely on that firm’s knowledge that such device was being prescribed or used by health care providers for such use.
FDA Will Use “Any Relevant Source of Evidence” to Determine Intended Use
Finally, several industry comments challenged the scope of evidence FDA may use in an “intended use” analysis and claimed that FDA should be limited only to a firm’s promotional claims. FDA rejected this claim and stated that nothing in the FDCA requires FDA to restrict its analysis to promotional claims when determining intended use. FDA maintains that this is consistent with its long-standing position that an intended use determination is a holistic analysis, and that FDA can use any relevant evidence. FDA also added the phrase “design or composition of the article” as within the scope of evidence FDA may use to determine intended use.
Overall, these changes bring the rules more in line with FDA’s current practices for intended use determinations and clarify some off-label and scope of evidences issues. Importantly, the changes – and the preamble to the final rules – make it clear that FDA will continue to rely on many sources of information when determining intended uses. Firms should also be mindful of these rules when they promote their products so they do not unintentionally create new intended uses.
Please reach out to the health care attorneys at Reed Smith if you have any questions about this regulatory change or any other FDA related inquiries.