Previous New Dietary Ingredient Notifications (NDINs) for cannabidiol (CBD) products, i.e., NDINs #984, #1116, #1117, #1128, and #1135, were not filed based solely on FDA’s determination that with limited exceptions, a substance such as CBD, which is an active ingredient in an approved drug (i.e., Epidiolex) or has been the subject of substantial, publicly known clinical investigations, is excluded from the legal definition of “dietary supplement.”  Although FDA has also consistently maintained there are substantial safety gaps that need to be addressed, these previously submitted NDINs were refused without a safety evaluation.

In a departure from previous responses that refused NDINs solely on the basis that CBD products are excluded from the dietary supplement definition, FDA’s letters dated July 23, 2021 and posted on August 11, 2021, responding to NDIN #1199 for Irwin Naturals – “Full Spectrum Hemp Extract” and NDIN #1202 for Charlotte’s Web – “Full Spectrum Hemp Extract,” indicate that FDA went on to review the safety data and found it did not reach the “will reasonably be expected to be safe” standard.  Safety data gaps noted in FDA’s letters include:

• Evidence on a general history of use was vague and did not provide an adequate description of the cannabis preparations (e.g., composition), serving levels, or frequency and durations of use for comparison to the currently proposed ingredient use.

• Preclinical and clinical studies on different phytocannabinoid mixtures were, in some cases, not completely characterized and could not be compared to the current ingredient.

• Most importantly, certain reported toxicity endpoints of CBD such as hepatotoxicity and reproductive toxicity, were not adequately addressed.

FDA’s taking the additional step of commenting on safety, after concluding that CBD is not an eligible dietary ingredient, reinforces that unresolved safety concerns could prevent the legal marketing of dietary supplements (as well as food) containing CBD, even if legislative action were to otherwise clear a regulatory pathway.  Keller and Heckman will continue to monitor and report on developments that impact the use of CBD in FDA regulated products.