Marijuana Regulatory Update: FDA Concludes CBD Products Are Not Dietary Supplements
June 17th, 2015
In its recently published “FDA and Marijuana: Questions and Answers,” the U.S. Food and Drug Administration (FDA) announced that products containing cannabidiol (CBD), a non-narcotic component of Cannabis sativa, cannot be marketed as dietary supplements because CBD is the subject of an FDA regulated clinical investigation. FDA’s conclusion could be problematic for the growing number of companies marketing and distributing cannabis-based products in states that have legalized marijuana. If these companies continue to market products containing CBD as dietary supplements, FDA could launch enforcement actions against them based upon the allegation that they are selling unapproved new drugs.
How is CBD regulated?
The entire Cannabis plant is listed as a Schedule 1 substance by the Drug Enforcement Administration’s Office of Diversion Control, making trade of any component of the plant illegal in nearly all circumstances under federal law. However, twenty-three states and the District of Columbia have passed laws allowing the use of medical marijuana within their borders. Additionally, voters in four states—Alaska, Colorado, Oregon, and Washington—and the District of Columbia have passed initiatives allowing recreational use of marijuana within their borders. These laws have created a market for an entirely new industry of products containing cannabis-derived substances including foods and dietary supplements. Although FDA has remained largely silent on how products containing cannabis-derived substances are regulated under federal law, it has recently published its policy that products containing CBD cannot be marketed as dietary supplements.
What is a dietary supplement?
Dietary supplements are defined and regulated pursuant to the federal Food, Drug, and Cosmetic Act (FDCA) (21 USC § 321(ff)) as a type of food product intended to supplement the diet that contains one or more dietary ingredients. Dietary ingredients include vitamins, minerals, herbs, botanicals, amino acids, concentrates, metabolites, constituents, and extracts.
To be lawfully marketed as a dietary supplement under the FDCA, a product must essentially meet four criteria: the product must (1) be intended to be ingested orally, (2) not be represented for use a conventional food or sole item of a meal or diet, (3) be labeled as a dietary supplement, and (4) contain one or more compliant dietary ingredients.
The FDCA, along with its related regulations, dictate what constitutes a compliant dietary ingredient that can lawfully be included in the formula of a dietary supplement. We will focus here on one such provision of the FDCA, 21 USC § 321(ff)(3)(B)(ii).
21 USC § 321(ff)(3)(B)(ii)
Many vitamins, minerals, herb, botanicals, and other similar articles are permissible dietary ingredients under the FDCA. However, the FDCA prohibits the use in dietary supplements of certain articles that are the subject of research for pharmaceutical uses. Specifically, the FDCA states that dietary supplements cannot contain:
an article authorized for investigation as a new drug, antibiotic, or biological for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public, which was not before such approval, certification, licensing, or authorization marketed as a dietary supplement or as a food unless the Secretary, in the Secretary’s discretion, has issued a regulation, after notice and comment, finding that the article would be lawful under this chapter. (21 USC § 321(ff)(3)(B)(ii).)
This provision prohibits articles studied under an investigational new drug application (IND) from use in dietary supplements if those articles were not marketed as part of a dietary supplement or food prior to the start of the study or research. In order to bring a new pharmaceutical to market in the United States, the sponsor of the pharmaceutical product must go through FDA’s IND process. Once a sponsor’s IND is approved by FDA, the sponsor can begin clinical trials into the safety and efficacy of that drug product for human beings for a specific intended use. Most approved INDs are publically available on www.ClinicalTrials.gov.
The Pyridoxamine Example
Applying this FDCA prohibition, in 2009, FDA responded to a citizen petition filed on behalf of a pharmaceutical company studying the effects of pyridoxamine, a type of vitamin B6, for diabetic nephropathy. (Read FDA’s 2009 response here.) FDA determined that products containing pyridoxamine could not be dietary supplements lawfully marketed within the FDCA because pyridoxamine was authorized for investigation as a new drug pursuant to a publically announced clinical trial. The FDA concluded that no independent, verifiable evidence existed showing pyridoxamine had been marketed as a food or dietary supplement prior to implementation of the clinical investigation into the article. Consequently, companies marketing pyridoxamine supplements could no longer lawfully do so. These companies were forced to remove those products from the market or risk enforcement action by FDA.
In FDA’s response to the citizen petition, the agency further clarified the types of articles included under 21 USC § 321(ff)(3)(B)(ii). FDA determined that an “article authorized for investigation as a new drug” includes both the active ingredient, like pyridoxamine hydrocholoride, as well as the active moiety, like pyridoxamine. (See FDA’s definition of ‘active moiety’ here.) FDA used its conclusion in this pyridoxamine case as an example in its 2011 guidance document, “Draft Guidance for Industry: Dietary Supplements: New Dietary Ingredient Notifications and Related Issues,” which can be read in full by clicking here, stating:
[A]ssume that Substance A, which is a constituent of a plant and has never been marketed as an article of food or as a dietary supplement, is a botanical dietary ingredient under section 201(ff)(1)(C) of the FD&C Act. A drug company is studying a salt of Substance A, “Substance A hydrochloride,” as an investigational new drug under an IND. In this situation, the relevant article for purposes of whether Substance A can be used in a dietary supplement is not Substance A hydrochloride, but Substance A itself, because Substance A is the active moiety that is being studied for its possible therapeutic action. Any compound that delivers Substance A is excluded from being used in a dietary supplement.
FDA’s determination with regard to pyridoxamine expands the number and types of articles that cannot be included as compliant dietary ingredients in dietary supplement formulations.
Why did FDA conclude products containing CBD are not dietary supplements?
FDA’s recently released Q&A page states:
Based on available evidence, FDA has concluded that cannabidiol products are excluded from the dietary supplement definition under section 201(ff)(3)(B)(ii) of the FD&C Act. Under that provision, if a substance (such as cannabidiol) has been authorized for investigation as a new drug for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public, then products containing that substance are outside the definition of a dietary supplement. There is an exception if the substance was “marketed as” a dietary supplement or as a conventional food before the new drug investigations were authorized; however, based on available evidence, FDA has concluded that this is not the case for cannabidiol.
It is likely that FDA reached this conclusion because GW Pharmaceuticals began a clinical trial in 2013 under an FDA-approved IND to study a pure, synthetic form of CBD for the treatment of childhood epilepsy. FDA has concluded that without evidence of prior marketing of CBD as part of a supplement or food product, GW Pharmaceuticals’ IND application prohibits any manufacturer from marketing a dietary supplement with CBD as an ingredient. However, FDA does indicate that it will consider any evidence submitted to demonstrate that prior to the IND filing, the ingredient was marketed as part of a supplement or food product. FDA’s recent announcement states “[i]nterested parties may present the agency with any evidence that they think has bearing on this issue.”
What does this mean for dietary supplements containing CBD?
Uncertainty surrounds the future of dietary supplements containing CBD. FDA’s current policy is clear in that products containing CBD cannot be marketed as dietary supplements. However, that policy could change should an entity or individual submit evidence to FDA that CBD has been marketed as part of a food or dietary supplement prior to the start of GW Pharmaceutical’s clinical trial in 2013.
Alternatively, if a dietary supplement manufacturer were to demonstrate that the CBD that is the subject of GW Pharmaceutical’s clinical trial is somehow different from the CBD that is utilized in the marketed supplements, the prohibition of 21 USC § 321(ff)(3)(B)(ii) may not apply. (Other new dietary ingredient regulations and policies would likely then apply but that will be the subject of a future post.) Given FDA’s determination in the pyridoxamine this case would be very difficult position to take as the agency’s current policy would exclude any compound that delivers CBD, including CBD and any derivatives of CBD.
Will FDA use the CBD determination as a basis for enforcement actions?
In the agency’s “FDA and Marijuana: Questions and Answers,” the following question and answer are offered:
- Will FDA take enforcement action regarding cannabidiol products that are marketed as dietary supplements?
- When a product is in violation of the FD&C Act, FDA considers many factors in deciding whether or not to initiate an enforcement action. Those factors include, among other things, agency resources and the threat to the public health. FDA also may consult with its federal and state partners in making decisions about whether to initiate a federal enforcement action.
Without providing a clear answer to the question, FDA has indicated that it is preserving its authority to take enforcement action against companies that market dietary supplements containing CBD.
In February of 2015, FDA issued warning letters to six companies marketing products claiming to contain CBD (interestingly, FDA notes that some of these were products were tested and shown to not actually contain CBD). However, the violations cited in these letters related primarily to the claims made about the products and the intended uses these companies ascribed to the various CBD products. These warning letters did not cite 21 USC § 321(ff)(3)(B)(ii) as a reason for issuance of the letters.
An FDA warning letter is “issued only for violations of regulatory significance,” which are “violations that may lead to enforcement action” if not corrected swiftly. (FDA Regulatory Procedures Manual 4-1.) Recipients of warning letters are typically granted 10-15 days to correct violations and respond to FDA. Failure to correct such violations or respond to the agency could result in more sever enforcement actions, like injunctions, seizures, and other penalties.
FDA has not yet utilized enforcement mechanisms applying this policy prohibiting CBD in dietary supplements based on 21 USC § 321(ff)(3)(B)(ii). Further, the agency has yet to determine if it will utilize enforcement mechanisms as the market for different products containing marijuana and marijuana derivatives continues to expand. If adverse events stemming from these types of products are reported directly to FDA or through state health agencies, FDA could take action against companies distributing and manufacturing these products. Likewise, if companies or institutions engaged in clinical investigations engage in market discipline, petitioning FDA to actively prohibit the use of CBD in supplements pursuant to 21 USC § 321(ff)(3)(B)(ii), the manufacture and distribution of these types of products will be negatively affected, like the case pyridoxamine in 2009.
Companies in the growing marijuana products industry will need to stay abreast of these federal regulatory issues and aware of possible enforcement actions to prepare for and, hopefully, avoid adverse consequences. For more information regarding how the FDA regulates the use of CBD in dietary supplements and other products, please contact us at firstname.lastname@example.org.