This article has been prepared by Doctor of Pharmacy Candidate, Lauren Miller.
The FDA guidance document is an update to clinical research guidelines following a list of questions that had been posed within a forum. These questions relate to the research requirements for the development of drugs that contain cannabis or compounds derived from cannabis. Drugs that contain cannabis and cannabis-compounds are subject to the same quality standards that other FDA-regulated products must comply to. However, the 2018 Farm Bill (under the Agriculture Improvement Act of 2018) changed the definition of hemp, a cannabis containing substance, and its control status under the Controlled Substances Act (CSA). The law removed hemp as a subset of marihuana as long as it contains less than 0.3 percent by dry weight of delta-9 tetrahydrocannabinol (THC), which no longer qualifies hemp as a controlled substance. If the raw materials, extract, or derivative contains a delta-9 THC concentration of 0.3 percent or higher at dry weight, it will fall under a Schedule I controlled substance. Growing and manufacturing products that exceed the 0.3 percent THC level must comply to the CSA and DEA requirements for the Schedule I compounds. For years, the only legal source of cannabis for clinical trials in the United States was the National Institute on Drug Abuse (NIDA) Drug Supply Program (DSP) lead by the University of Mississippi at the National Center for Natural Products Research. The changes within the 2018 Farm Bill, allows for hemp to serve as a legal source for cannabis products under drug development if they follow the FDA requirements and new definition for hemp. This change allows for more sponsors to complete testing and clinical studies, however the FDA has provided new provisions for the quality and testing that must occur.
As part of an Investigational New Drug (IND) for products containing cannabis or cannabis compounds, sponsors are required to prove that their product quality can be replicated. As a product progresses through trial phases, information of identity, quality, purity, and potency of the drug must be provided. Data regarding any phytochemicals present in the drug including cannabinoids, terpenes, and flavonoids should be stated. Since cannabis is listed as a botanical product, there are core principles described by the Botanical Drug Development that the IND must comply to: characterization of cannabis through a chemical fingerprint ensuring consistency; testing for pesticides (USP 561); USP 563, 61, 232 testing for origin, sterility, and impurities; quality tests per dosage form; and scheduling consideration under the CSA for abuse potential. Special considerations should be taken for storage information to preserve the integrity of the product and ensure the dosage form is protected from leachable compounds (USP 1663). Before testing of a product can occur, proper calculations must be made to comply with the definition of hemp with analytical testing. The FDA may require further testing from the sponsor’s data if a scheduling concern becomes apparent. When presenting data to the FDA with an IND application, quantitative data from the lab analysis indicating the THC percentage by dry weight in the botanical raw material as well as descriptions of the testing methods used to evaluate the THC levels must be provided. If the proposed drug is a solution or an extract, the defined calculation for composition of the raw material does not apply. The calculation should instead be based on the calculation of delta-9 THC percentage with the amount of water removed, including any water that may be in excipients. For all other dosage forms, the amount of the compound of interest (THC) naturally present relative to the dry weight of botanical raw material prior to manufacturing should be used to calculate THC concentration. All of these processes stated and others, like dosing regimen and single dose packaging, will be evaluated with the IND application as stated.
More information and the full draft guidance is available on the FDA’s website:
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