On July 21, 2020, the U.S. Food and Drug Administration issued its draft guidance on clinical research for the development of drugs that contain cannabis or cannabis-derived compounds of botanical origin (as opposed to synthetic). The draft guidance isentitled “Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research, Draft Guidance for Industry.” The guidance provides some clarity on the use of cannabis in clinical research in light of the changes made by The Agriculture Improvement Act of 2018, Public Law 115-334 (the 2018 Farm Bill) which federally legalized hemp and cannabis derivatives that contain no more than 0.3 percent THC on a dry weight basis. Specifically, the draft guidance outlines the FDA’s “current thinking” on: (1) the source of cannabis and cannabis-derived compounds for clinical research; (2) quality considerations for developing drugs that contain cannabis and cannabis-derived compounds; and (3) how to calculate the THC percentage in botanical raw materials, extracts, and finished products.
Source of cannabis and cannabis-derived compounds
The draft guidance lists the two sources of cannabis for clinical research: the federally authorized marijuana manufacturer at the University of Mississippi, which is the only entity legally permitted to conduct clinical research of products with over a 0.3 percent THC level, and researchers conducting clinical research on products below the 0.3 percent THC level threshold. The draft guidance reminds stakeholders that activities related to growing and manufacturing cannabis for use as an investigational drug for research must comply with CSA and DEA requirements and encourages researchers to contact the Drug and Enforcement Administration with proposals for drug development activities involving THC levels above the legal threshold.
Quality considerations
The draft guidance explains that researchers are expected to show that they can consistently manufacture a quality product by submitting information as to the “identity, quality, purity, and potency or strength of the investigational drug” as well as “quantitative data regarding phytochemicals that are present in their proposed product, including but not limited to, cannabinoids, terpenes, and flavonoids.” Researchers are directed to a number of resources for quality considerations, including guidance for CGP for Phase 1 Investigational Drugs (July 2008), Analytical Procedures and Methods Validation for Drugs and Biologics (July 2015) and Q2(R1) Validation of Analytical Procedures: Text and Methodology (March 1995). Researchers are recommended to pay particular attention to the guidance for industry Botanical Drug Development (December 2016) which provides “core principles for conducting clinical research on botanical drugs.”
Calculation of THC levels
The draft guidance recommends that researchers “calculate the level of delta-9 THC in their proposed investigational drug product early in the development process to gain insight into the potential control status of their product” and work with “reliable laboratories for analytical testing.” Furthermore, FDA recommends that applicants for an investigational new drug provide the FDA with “quantitative data, such as a certificate of analysis from a laboratory . . . indicating the percent of . . . THC by dry weight” and “detailed descriptions of testing methods used to evaluate the level of . . . THC.”
The draft guidance concludes with a detailed description of how researchers should calculate the dry weight of THC in botanical raw material and provides a breakdown based on the dosage form (e.g., solution-based or solid oral).
Industry Impact
This is the first guidance released by FDA, following the 2018 Farm Bill, which provides recommendations to the industry on drugs that contain cannabis or cannabis-derived compounds of botanical origin. While helpful, it largely follows the guidance already provided for general botanical drug development. The Agency has not imposed new quality standards or considerations for these products.
The Agency’s principles and recommendations for botanical raw material, botanical drug substance, or botanical drug product remain applicable and are fundamentally well developed. The Botanical Review Team at FDA continues to serve as the expert resource on botanical issues and the Botanical Drug Development Guidance for Industry remains the primary resource to assist those pursuing drug development in this area. Considering the FDA’s previous statements provided on its website (FDA and Cannabis: Research and Drug Approval Process), this guidance’s most notable takeaway is the FDA’s clear and direct statement that clinical research on products containing less than 0.3 percent THC can be openly sourced and researchers are not limited to procurement through the National Institute on Drug Abuse (NIDA) Drug Supply Program.
We expect to continue to see the industry pursue research in the cannabis and cannabis-related product space with a marked uptick as access to cannabis and cannabis-derived compounds increases. The Agency’s guidance signals its focus on providing transparency to stakeholders and its recognition that industry is looking to speed the development of these products through clear and streamlined regulatory pathways.
