Key Takeaways

• The FDA issued finalized industry guidance for using cannabis and cannabis-derived compounds in clinical research
• The guidance details standards and requirements for investigational new drug applications involving cannabis

On Jan. 23, the Food and Drug Administration (FDA) finalized industry guidance for clinical research using cannabis and cannabis-derived compounds, Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research. The need for the guidance stemmed from the 2018 Farm Bill, which legalized the production and sale of hemp (cannabis below 0.3 percent delta-9 THC by dry weight) and removed it from the Schedule I substance list. Drugs containing cannabis or its derivates remain under FDA regulation and are generally subject to the same requirements and quality standards as any other FDA-regulated drug. The finalized guidance outlines FDA regulatory concepts and mechanisms and provides three key recommendations for investigational new drug sponsors interested in using the products in clinical research.

1. Sources of Cannabis

The National Institute on Drug Abuse (NIDA) Drug Supply Program (DSP) is no longer the only domestic, federally legal source of cannabis for clinical research. Sponsors and investigators may now source cannabis over the 0.3 percent delta-9 THC threshold from the NIDA DSP or other sources, if authorized by the Drug Enforcement Administration (DEA). The FDA refers sponsors and investigators to the DEA for guidance regarding importation, production and sourcing for cannabis research.

2. Resources for Information on Quality Considerations

As for any investigational new drug, sponsors for drugs containing cannabis and its derivates are expected to demonstrate consistency in manufacturing and submit data to prove identity, quality, purity, and potency or strength of the drug. The guidance defers to previous agency guidance outlining recommendations for each phase of investigations, including data collection, Current Good Manufacturing Practices, and how to address chemistry, manufacturing and controls. The agency continues to note that cannabis and cannabis-derived compounds are held to the same regulatory standards as any other botanical raw material, botanical drug substance or botanical drug product. Specifically, the guidance includes recommendations on testing and data collection, listing applicable United States Pharmacopeia chapters for testing quality, and assessments of packaging and delivery systems.

3.  Considerations of Control Status Under the CSA

The guidance cautions that cannabis with a delta-9 THC concentration higher than 0.3 percent must still comply with Controlled Substance Act (CSA) and DEA requirements. The guidance details how to calculate THC concentration to determine control status. Additionally, the agency refers sponsors to the DEA and CSA when working with cannabis products and recommends sponsors determine the THC concentration early in the drug development process to establish product insight and control status.

Overall, the FDA’s guidance details how investigational new drug work and sponsors can prepare for a new drug application by addressing basic standards and requirements. Currently, the FDA has approved only one cannabis-derived drug, Epidiolex from Jazz Pharmaceuticals, for a rare epilepsy disorder. The drug contains cannabidiol, the non-psychoactive compound found in cannabis. However, the finalization of this guidance provides a clearer pathway for researchers to source, test and secure approval of cannabis and cannabis-derived drugs.

Authorship credit: Lee H. Rosebush (Partner); Randal M. Shaheen (Partner); Winston S. Kirton (Partner); Laura E. Macherelli (Associate)