By Suzan Onel
While the Food and Drug Administration (“FDA”) has issued numerous warning letters to companies marketing cosmetic, food, dietary supplement, and other consumer products that include cannabidiol (CBD), these warning letters have been primarily related to products with disease-related claims which FDA asserted rendered them drugs. Recently FDA issued two warning letters that specifically address the use of cannabidiol (CBD) as an ingredient in over-the-counter (“OTC”) drug products. See Honest Globe, Inc. (“Honest Globe”) (March 15, 2021) BioLyte Laboratories, LLC (“BioLyte”) (March 18, 2021). These warning letters are notable and deserve close scrutiny for their potential impact on the OTC drug marketplace.
Both warning letters focused on product claims for CBD-containing topical OTC pain relieving products that appeared on product labeling, websites, blogs, and other forms of social media, such as Instagram. Notably, in both cases, the warning letters followed from FDA inspections where the agency found significant violations of current good manufacturing practice regulations for finished pharmaceuticals (cGMPs) and raised other significant labeling issues.
In both warning letters, FDA points to numerous examples of labeling and marketing claims that allegedly represent CBD as an active pharmaceutical ingredient even though the companies list CBD as an inactive ingredient. FDA concludes that they are “new drugs” within the meaning of Section 201(p) of the Federal Food, Drug, and Cosmetic (“FDC”) Act, 21 USC 321(p), and that they are “unapproved new drugs” marketed in violation of the FDC Act since none of the listed products are the subject of an FDA-approved application and none meet the new eligibility requirements for marketing under the CARES Act. Sections 505(a) and 301(d) of the FDC Act, 21 USC 355(a) and 331(d).
More interestingly, FDA states in both warning letters that even if the products were properly labeled and the claims did not imply that CBD is an active ingredient, the products would still be unapproved new drugs because CBD does not qualify as an inactive ingredient. FDA bases this conclusion on the following:
- (1) Under 21 CFR 330.1(e), inactive ingredients must be safe and suitable.
- FDA states in both warning letters, “[A] suitable inactive ingredient generally provides a beneficial formulation function, such as a tablet binder or preservative, or improves product delivery (e.g., enhances absorption or controls release of the drug substance).CBD has no known functional role as an inactive ingredient in a finished drug product.” (Emphasis added.)
- (2) Under 21 CFR 314.3(b) and 21 CFR 210.3(b)(7), an active ingredient is a component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man.
- FDA states in both warning letters, “[A]n inactive ingredient should not exert pharmacologic effects and must be safe when used at the intended dosage. CBD, however, has known pharmacological activity with demonstrated risks.” (Emphasis added).
The agency advised both companies to take prompt action to correct this and the other alleged violations cited in the letters, adding that failure to correct the alleged violations may result in legal action without further notice, including, without limitation, seizure and/or injunction.
While the two warning letters could be read as ostensibly blocking any use of CBD in OTC drug products, there are some interesting legal gaps in the FDA’s analysis. For example, to support its position that CBD is not a suitable inactive ingredient, FDA cites guidances regarding excipients in FDA approved drugs. See footnote 6 in the Honest Globe warning letter. Arguably these documents do not apply to OTC drugs covered by a tentative or final monograph. In fact, there is legal support for the position that if CBD performs a technical function that has been recognized as being appropriate for inactive ingredients and can be substantiated, the ingredient could be suitable as an inactive ingredient.
Similarly, to support its position that CBD is not a safe inactive ingredient in topical OTC drugs, FDA refers to the pharmacological activity CBD has in Epidiolex, an approved oral drug. However, as FDA acknowledges in both warning letters, it does not know what levels of CBD are used in the products. To Honest Globe, FDA wrote: “It is unknown whether the levels of CBD used in your ‘Elixicure Pain Relief with CBD’ products have pharmacological activity or pose any concern for safety events.” To BioLyte, FDA wrote: “It is unknown whether the levels of CBD used in your ‘… Pain Relief Cream’ and ‘… Therapeutic Pain Gel’ products have pharmacological activity or pose any concern for safety events.” Accordingly, there may be an opportunity to rebut FDA’s assertion about pharmacological activity and risk by establishing scientific support that a CBD ingredient included in a particular formulation qualifies as “safe” at the amount included and based on the dosage form and the product’s labeled directions for use.
It remains to be seen whether these warning letters signal a heightened FDA focus or enforcement interest in the use of CBD in the OTC drug marketplace or if they were mainly prompted by a confluence of issues that were specific to these two companies. Regardless, the letters provide important insight into FDA’s current thinking about the role of CBD as an inactive ingredient in an OTC drug product and is an area we will continue to closely monitor.