The U.S. Food and Drug Administration (FDA) recently issued draft guidance to further the development of drugs that contain cannabis and compounds found in cannabis, acknowledging the growing interest in this area. The guidance, Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research (Cannabis Guidance), addresses key manufacturing and testing issues for FDA regulatory submissions, including applications to begin clinical trials. These considerations include cannabis sources, quality, and calculation of delta-9 tetrahydrocannabinol (THC) concentration in botanical raw materials, extracts, and highly purified substances of botanical origin.
Medical product cannabis has historically been a difficult ingredient to source. For many years, the National Institute on Drug Abuse (NIDA) provided the only domestic federally legal source of cannabis for clinical research. However, the 2018 Farm Bill improved sourcing possibilities by allowing hemp to serve as a source of cannabis and cannabis-derived compounds for drug development if they do not contain THC more than 0.3 percent by dry weight. The FDA’s recent guidance clearly indicates that cannabis at or under the 0.3 percent THC limit may now be used for clinical research without NIDA negotiations and provides recommendations for calculating the THC concentration. The basis and determination of the THC concentration in cannabis and cannabis-derived compounds can vary depending on drug dosage form and is a key piece of an investigational new drug (IND) application to initiate a clinical study.
In an IND application, sponsors are also expected to show that they can consistently manufacture a quality product by submitting information to ensure the identity, quality, purity, and potency or strength of the investigational drug. The same expectation holds true for drugs that contain cannabis or cannabis-derived compounds. In particular, applications for these types of investigational drugs will require quantitative data regarding phytochemicals including cannabinoids, terpenes, and flavonoids. To help sponsors determine the appropriate data for submission, the Cannabis Guidance refers readers to well-known FDA guidances addressing drug quality for stakeholders who may be less familiar with FDA authorities than other drug developers.
Approximately one week after releasing the Cannabis Guidance, the FDA announced it had authorized the only FDA-approved drug that contains a purified drug substance derived from cannabis, Epidiolex, for a new indication. Epidiolex was previously approved for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS). The drug’s most recent approval is for the treatment of seizures associated with tuberous sclerosis complex (TSC) in patients one year of age and older. This application was granted Priority Review by the FDA, a designation for select drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications. In the news release announcing approval of the TSC indication, the FDA stated it is “committed to supporting rigorous scientific research on the potential medical uses of cannabis-derived products and working with product developers who are interested in bringing patients safe and effective, high quality products.”
The Cannabis Guidance and latest Epidiolex approval are part of a larger initiative within the FDA to both foster and regulate cannabis medical products. As mentioned in a previous alert, one of the first press announcements from the current FDA commissioner related to advancements in cannabis policy. The FDA has also taken steps to interact with stakeholders on regulating cannabis. A public docket was originally opened on April 3, 2019 to obtain scientific data and information about the safety, manufacturing, product quality, marketing, labeling, and sale of products containing cannabis or cannabis-derived compounds. Following a widely-attended FDA public meeting, the docket was re-opened due to “continued interest and increased research activity in this space, as well as the need for additional scientific data on this topic.”
Readers are encouraged to evaluate the potential impact of the Cannabis Guidance. As the guidance is in draft form and open to public comment, it provides an opportunity to influence the agency’s thinking on regulatory policy with outcomes that affect how products come to, and remain on, the market.