On Tuesday, July 21, 2020, the U.S. Food and Drug Administration (FDA) issued “Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research, Draft Guidance for Industry.” While it contains little “new news,” the draft guidance describes FDA’s current thinking on several topics relevant to clinical research related to development of drugs containing cannabis or cannabis-derived compounds, including sources of cannabis for clinical research, information on quality considerations and recommendations regarding calculating delta-9 tetrahydrocannabinol (THC) levels. The draft guidance also introduces key FDA regulatory concepts to stakeholders who may be less familiar with the FDA and the FDA’s authorities.
FDA’s draft guidance begins with a review of the effects of the 2018 Farm Bill, which decriminalized hemp, defined as cannabis with a concentration of THC at or below 0.3% on a dry weight basis. Accordingly, hemp is now legal at the federal level and subject to the control of the United States Department of Agriculture and FDA. Marijuana, defined as cannabis with more than 0.3% THC, remains federally illegal and is subject to the Controlled Substances Act (CSA) and the authority of the Drug Enforcement Administration and other criminal law enforcement agencies.
With that background in mind, FDA’s draft guidance begins by noting that, for many years, cannabis could only be sourced from the National Institute on Drug Abuse (NIDA) Drug Supply Program (DSP), but that is no longer the case. Now, as a result of the removal of hemp from the CSA, researchers can source hemp from cultivators who produce their product pursuant to a state, tribal, or other USDA approved plan. The draft guidance then states, however: NIDA DSP remains the only domestic federally legal source of cannabis over the 0.3 % THC limit for clinical research.
Second, the guidance makes it clear that cannabis is held to the same regulatory standards as any other botanical raw material, drug substance or drug product. Accordingly, existing FDA guidance governing those issues should be consulted. While FDA has identified additional principles and documents for those pursuing drug development using cannabis or cannabis-derived compounds, it also noted that published studies should not be relied upon in place of a full toxicological program.
Finally, one particularly noteworthy element of the draft guidance is FDA’s relatively detailed discussion of the 0.3% THC concentration limitation for what constitutes hemp. FDA states unequivocally that activities related to growing and manufacturing cannabis for use as an investigational drug for research must comply with CSA and DEA requirements. FDA makes it clear that THC levels should be tested at each phase of development during the research process, highlighting concerns about THC levels not only in raw forms of cannabis (i.e. hemp and marijuana plants), but in all forms of cannabis-derived products, including for example where a manufacturing process generates materials, such as intermediates or accumulated by-products, that exceed the 0.3% THC threshold even if the source material or finished product does not exceed the threshold. The practical result of this requirement is that cannabis and cannabis derivatives must maintain a THC level at or below 0.3%, with no identified margin of error. This can be difficult to ensure because THC levels are susceptible to outside influences, some of which may be beyond growers, researchers, or manufacturers’ control.
The comment period is open until September 21, 2020. We will continue to monitor this topic for further developments.
Our Cannabis Practice provides advice on issues related to applicable federal and state law. Marijuana remains an illegal controlled substance under federal law.