On December 9, 2022, FDA issued a proposed rule that would create an exemption from investigational new drug (IND) requirements for certain clinical studies on drug uses of lawfully marketed cosmetics and human food, including dietary supplements, medical foods, and infant formula. FDA finalized somewhat controversial guidance in 2013 setting forth certain circumstances under which FDA had concluded that clinical research on food and cosmetics could be conducted without an IND. After receiving significant pushback, FDA stayed certain parts of the final guidance for further consideration.
This proposed rule would provide for certain IND exemptions, which would expand the scope of clinical studies that can be conducted on human food and cosmetics without an IND to include certain studies on drug uses. Studies on human food and cosmetics for non-drug uses are already not subject to IND requirements.
Under the proposed rule, sponsors could self-determine that they are exempt from IND requirements for a clinical study to evaluate a drug use of a human food or cosmetic lawfully marketed in the U.S. under the following circumstances:
- The investigation is not intended to support (i) a drug development plan, including a future IND or drug marketing approval, or (ii) a change in labeling that would cause the product to be unlawfully marketed as a drug;
- The investigation complies with institutional review and informed consent requirements;
- The sponsor complies with 21 CFR 312.7, including by not representing that the test article is safe or effective for the drug purpose for which it is under investigation;
- The route of administration is the same as that of the lawfully marketed product; AND
- The investigation meets all of the following subject health, safety, and welfare criteria:
a. The investigation does not include subjects who are less than 12 months of age or subjects who are pregnant or lactating,
b. The investigation does not include subjects with a compromised immune system or a serious or life-threatening disease or condition,
c. The investigation does not restrict subjects from continuing with treatments or therapies prescribed or recommended by a healthcare provider,
d. The investigation does not involve procedures that would abnormally increase risks or decrease the acceptability of risks,
e. The product is being investigated consistent with its labeled or ordinary conditions of use, AND
f. The subjects are not taking and will not be treated with any other products that would significantly increase risks (e.g., through drug interactions).
Sponsors that self-determine their exempt status are not required to notify FDA of their determination. FDA can issue an untitled or warning letter to a sponsor, or take other regulatory or enforcement action, if it finds that the self-determination does not comply with the above criteria.
The proposed rule would also create a second pathway for IND exemption: through a request granted by FDA, which the proposed rule calls the “FDA-determined exemption.” Sponsors can request an exemption from FDA when an investigation meets the criteria listed in numbers 1-4 above, but does not meet all of the subject health, safety, and welfare criteria listed under number 5. The exemption request must be made in writing and explain why the investigation does not present a potential for significant risk to the health, safety, or welfare of subjects. The request should also include a copy of the study protocol or protocol summary and product labeling for the lawfully marketed food or cosmetic, among other information.
FDA did not propose to establish a specific timeline under which it would review and act upon IND exemption requests. Even if an exemption request is granted, FDA would be able to revoke the exemption if it learns of new information that could present a potential for significant risk to the health, safety, or welfare of subjects, or that the investigation no longer meets the requirements under numbers 1-4.
Overall, this proposed rule would expand the types of research that could be done on food and cosmetics without an IND compared to FDA’s current approach. For example, FDA’s position under the 2013 guidance is that INDs are not required when food is studied for safety or tolerability, but an IND would be required if the investigation evaluated the effect of a food on a disease. This position could be particularly challenging for foods that are intended for people with a particular disease or condition, as studies examining the efficacy of such foods could inherently involve an evaluation of the effect of the food on disease. The proposed rule would help to address this disconnect and instead more broadly exempt lawfully marketed food and cosmetics from IND requirements even when evaluated for a drug use.
While the proposal would not allow manufacturers to change their food or cosmetic labeling to make claims about a studied drug use, it would allow manufacturers to use these studies to support other compliant claims for the product category, such as lawful structure/function claims for dietary supplements.
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If you have any questions concerning the material discussed in this client alert, please contact the members of our Food, Drug, and Device practice.
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