The U.S. Food and Drug Administration (FDA) recently released the Draft Guidance for Industry, Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research. In this guidance, the FDA defers to the Drug Enforcement Administration (DEA) for products that fall under the DEA’s jurisdiction. However, the FDA does provide several useful pieces of information for sponsors and investigators developing drugs derived from cannabis.

Background

This guidance is the direct result of passage of the Agriculture Improvement Act of 2018 (2018 Farm Bill).[1] With its passage, the 2018 Farm Bill removed the hemp plant from the Controlled Substances Act (CSA).[2] Specifically, the 2018 Farm Bill defined hemp as:

[T]he plant Cannabis sativa L. and any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a delta-9 tetrahydrocannabinol [(THC)] concentration of not more than 0.3 percent on a dry weight basis.[3]

Accordingly, Section 12619 of the 2018 Farm Bill amends the CSA[4] by removing hemp from the definition of marijuana[5] and by de-scheduling components derived from hemp containing a low concentration of THC.[6]

The healthcare industry is interested in the 2018 Farm Bill because the definition of hemp now means that if the THC[7] concentration is less than 0.3 percent on a dry weight basis, the plant Cannabis sativa L. and any part of that plant is not a controlled substance under the CSA.[8] Historically, all parts of the Cannabis sativa L. plant were classified as Schedule I controlled substances under the CSA.[9] Schedule I means that there is no accepted medical use, although research may be conducted under strict controls.[10] Accordingly, after the 2018 Farm Bill, hemp, including hemp plants and cannabidiol preparations at or below the 0.3 percent delta-9 THC threshold, is not a controlled substance, and a DEA registration is not required to grow or conduct research on it.

What does this guidance provide?

The FDA guidance provides clarification on three main issues related to the development of drugs derived from cannabis: sources of cannabis, resources for information on quality considerations and percent delta-9 THC calculation.

First, the FDA reaffirms that the DEA is the lead federal agency for regulating controlled substances. Thus, if a cannabis-derived compound exceeds the threshold of 0.3 percent delta-9 THC by dry weight, sponsors and investigators must comply with the CSA and DEA requirements. Cannabis below the 0.3 percent delta-9 THC threshold may be sourced from anywhere and used for clinical research because this cannabis is not a controlled substance. However, cannabis above the 0.3 percent delta-9 THC threshold is a Schedule I controlled substance. The National Institute on Drug Abuse Drug Supply Program is the only federally legal domestic source of cannabis containing more than 0.3 percent delta-9 THC.

Second, the FDA provides a bibliography of what resources should be consulted to ensure the identity, quality, purity and potency or strength of an investigational drug containing cannabis or cannabis-derived compounds.

Third, the FDA recommends that sponsors and investigators calculate the level of delta-9 THC in their proposed investigational drug product early in the development process to gain information about the composition of a proposed raw material, intermediate substance, drug substance or drug product. The guidance provides a recommended calculation, for which sponsors should provide documentation when an investigational new drug application is submitted to the FDA. If at any time in the manufacturing process any material, such as intermediates or accumulated byproducts, exceeds the 0.3 percent delta-9 THC by dry weight threshold, sponsors and investigators should consult with the DEA for recommendations on how to handle the material because the material would be considered a Schedule I controlled substance.

Future outlook

This draft guidance provides sponsors and investigators with much-needed insight regarding developing cannabis and cannabis-derived compounds. While this guidance pertains only to drugs, we anticipate that we may see future guidance or regulation on cannabis and cannabis-derived compounds marketed as dietary supplements.

[1] Agriculture Improvement Act of 2018, Pub. L. No. 115–334, 132 Stat. 4490 [hereinafter 2018 Farm Bill].
[2] Id. § 12619. For a brief description of the CSA, see infra note 4.
[3] 2018 Farm Bill, Pub. L. No. 115–334, § 10113, 132 Stat. 4490.
[4] 21 U.S.C. §§ 801 et seq. Prior to the 2018 Farm Bill, the CSA imposed both civil and criminal penalties “to manufacture, distribute, or dispense, or possess with intent to manufacture, distribute, or dispense, a controlled substance” with limited exceptions. Id.
[5] § 802(16).
[6] § 812(c).
[7] THC is the component in marijuana that produces a feeling of euphoria.
[8] Scientific Data and Information About Products Containing Cannabis or Cannabis-Derived Compounds; Public Hearing; Request for Comments, 84 Fed. Reg. 12969 (April 3, 2019).
[9] Id.
[10] 21 U.S.C. §812. THC remains a Schedule I controlled substance, but components derived from the Cannabis sativa L. plant with a THC concentration lower than 0.3 percent are not scheduled.