The US Food and Drug Administration has finalized a 2020 draft guidance outlining how sponsors and investigators can conduct clinical trials for certain drugs containing cannabis or cannabis-derived compounds without running afoul of federal law.
When Congress passed the Agriculture Improvement Act of 2018, also known as the 2018 Farm Bill, it defined hemp as including cannabis and derivatives or extracts of cannabis with “a delta-9 tetrahydrocannabinol (THC) concentration of not more than 0.3% on a dry weight basis.” That means low cannabis-concentration hemp is no longer considered marijuana and is no longer an illegal substance under the Controlled Substances Act (CSA). It also means such products are no longer under the purview of the Drug Enforcement Agency, which regulates controlled substances.
That change led the FDA to publish a draft guidance in 2020 that outlined its thinking on what drug developers need to do to stay in compliance with federal law while also meeting the agency’s requirements to prove cannabis or cannabis-derived compounds can be used in clinical research
On 20 January, the FDA finalized the guidance, which details how the agency regulates drugs in general but also its requirements for THC-containing products more specifically.
“Changes from the draft to the final guidance include clarifying sources of cannabis for clinical research (including Schedule I sources), adding resources explaining expectations for investigational new drug (IND) applications in various stages of drug development, and providing guidance on quality considerations for INDs,” the FDA said in announcing the final guidance.
The agency also reminded stakeholders that sponsors and investigators need to meet the regulations for conducting human clinical trials, regardless of the source of the cannabis or any other botanical product being studied in the trial. In the guidance, the agency lists resources on its website and references past guidances that drug sponsors should familiarize themselves with when developing a drug that includes cannabis.
The final guidance notes that the National Institute on Drug Abuse (NIDA) Drug Supply Program (DSP) through the University of Mississippi is no longer the only federally legal source for cannabis with a delta-9 THC level greater than 0.3%.
“Sponsors and investigators may use the NIDA DSP as a source of cannabis over the 0.3% delta-9 THC threshold, or they may use other sources authorized by DEA to provide Schedule I cannabis materials for research,” said the FDA. “Sponsors can find DEA regulations for importation of controlled substances in 21 CFR 1312.”
“A list of DEA-authorized growers of Schedule I cannabis is available online,” the agency added. “We refer sponsors and investigators to the DEA for guidance and answers to frequently asked questions about cannabis production and sources for research.”
A key consideration for the FDA is the quality and consistency of the cannabis source that sponsors use to develop an investigational drug. The agency wants sponsors to provide an adequate characterization of the cannabis and cannabis-derived compounds and conduct a full range of quality tests. The agency lists applicable United States Pharmacopeia chapters on quality testing in the final guidance, including the assessment of leachables from packaging and delivery systems.
The FDA cautions that hemp with THC concentration higher than 0.3% used for medical research still needs to comply with the CSA and DEA requirements. The guidance goes into detail about how to calculate the THC concentration to determine control status for cannabis and cannabis-derived compounds.
“Sponsors and investigators proposing drug development activities involving controlled substances should consult DEA about the applicable requirements,” the agency added, adding that they “may find it useful to calculate the delta-9 THC content in their proposed cannabis or cannabis-derived investigational drug product early in the development process to gain insight into their product’s potential abuse liability and control status.”
The guidance also includes relevant International Council for Harmonization (ICH) guidelines, FDA guidances, and other considerations for devices used in combination with a cannabis-derived drug.