Cannabis and cannabis-derived products (CDPs) have become increasingly prevalent throughout the medical community. More and more companies within the Life Sciences industry are exploring the potential use of cannabis to treat a variety of medical conditions. The Agriculture Improvement Act of 2018, often referred to as the Farm Bill, preserved FDA’s authority to regulate products containing cannabis or CDPs under the FD&C Act and section 351 of the Public Health Service Act. As such, human drugs that contain cannabis and CDPs are generally subject to the same requirements, including quality standards, as FDA-regulated drug products containing any other substance. It is critical for FDA to play a proactive role in ensuring clinical studies are appropriate to assess the effectiveness and safety of cannabis and CDPs and to enhance research on possible adverse health effects.
In that regard, FDA published final guidance titled “Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research” to provide recommendations for sponsors interested in developing cannabis and CDPs for use in human drugs for clinical research. Some of the main topics addressed in the guidance include:
Clarifying sources of cannabis for clinical research
- Sources of cannabis with not more than 0.3 percent delta-9 tetrahydrocannabinol (THC) on a dry weight basis and those over 0.3 percent delta-9 THC on a dry weight basis may be used for clinical research if deemed to be of adequate quality by FDA when reviewed as part of an IND.
- Sponsors and investigators may use the National Institute on Drug Abuse (NIDA) Drug Supply Program (DSP) as a source of cannabis over the 0.3 percent delta-9 THC threshold, or they may use other sources authorized by DEA to provide Schedule I cannabis materials for research. Sponsors can find DEA regulations for importation of controlled substances in 21 CFR 1312.
Resources for Information on Quality Considerations
- Sponsors must provide a description of the investigational drug substance, which should include quantitative data regarding phytochemicals that are present in their proposed drug, including but not limited to, cannabinoids, terpenes, and flavonoids.
- 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. The general recommendations for botanical drugs contained in the guidance for industry titled “Botanical Drug Development (December 2016)” provide core principles for conducting clinical research on botanical drugs, including drugs that contain cannabis and cannabis-derived compounds.
- Highly-purified substances of botanical origin are considered analogous to conventional synthetic single-chemical active pharmaceutical ingredients for the purposes of drug development and FDA review. However, a naturally occurring compound isolated from a botanical source would be expected to have a different impurity profile from the corresponding synthetically produced cannabis-related compound, and impurities for the naturally occurring compound should be controlled accordingly.
- If a device is to be used in combination with a drug, the product is considered to be a combination product and must comply with the CGMP requirements in 21 CFR part 4, subpart A, including requirements for design controls.
- Applicants should consider selection of a container closure system or device constituent part carefully. As drug development progresses, applicants pursuing FDA approval should generate adequate characterization information and safety assessment data for extractable and leachable compounds to support a marketing application.
- IND sponsors may submit literature to support early clinical development. However, in general, chemical composition information found in published studies of test materials is not adequate for bridging to a proposed botanical drug product because the particular botanical drug product under review may differ from that of the published study. Therefore, FDA does not recommend that applicants pursuing FDA approval of an NDA rely on published literature in place of data from a full toxicology program to support development of a botanical drug product for phase 3 trials and beyond.
- Assays to characterize the metabolic profile of major cannabinoids in humans and in toxicology species should be developed early to avoid delays in development.
If you need any assistance with Quality or Regulatory Compliance matters, please book an appointment with our CEO, Stefanie Wichansky . We understand how challenging it can be to maintain compliance while managing your day-to-day operations. We have a large, experienced team of QA/RA consultants throughout the country who can seamlessly integrate with your team to fill any gaps in expertise or bandwidth, ensuring you stay on track with your compliance goals. We would welcome the opportunity to work together!