The Medical Cannabis Research Advocacy Alliance (MCRAA) appreciates the opportunity to provide comments in response to the US Food and Drug Administration (FDA)’s Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research Draft Guidance for Industry; Availability 85 FR 44305 (July 22, 2020).

The draft guidance covers sources of cannabis and cannabis-derived compounds for clinical research, information on quality considerations and recommendations regarding the calculation of tetrahydrocannabinol (THC) levels.

This article was written by Dr. Theodore Zanker, MD, DLFAPA, DLFAACAP of the MCRAA. To read this article in the pdf version, click here.

Introduction to the MCRAA

MCRAA is a newly formed not-for-profit organization that was established to advance medical cannabis-based research, education and communication along with fair and transparent policies in the health care system associated with development of drugs containing cannabis and cannabis-derived compounds for the benefit of patients.

As part of this mission, MCRAA seeks to better understand the challenges facing physicians and their patients tied to clinical research and drug development associated with cannabis and cannabis-derived compounds and to educate policymakers about these challenges.

MCRAA’s Board of Directors is comprised of chief executive officers, presidents, and chief medical officers from several state medical associations, and national medical specialty associations; medical cannabis cultivators, manufacturers, distributors, and dispensaries; academic and medical research institutions; and patient advocacy and rights organizations.

As a physician led, patient focused association, we are equipped to provide comments and insight into many of the challenges tied to the development and medical use of drugs containing cannabis or cannabis-derived compounds.

Cannabis Research

It is important to recognize that cannabis research may take several forms, not all of which is sponsored research with the intention of developing and obtaining a therapeutic claim or indication. While this FDA guidance is aimed squarely at such pharmaceutical drug development, there is also a need for basic research focused on non-therapeutic cannabis use, such as the safety of driving or vaping.

These studies may be facilitated by allowing researchers access to cannabis products with a more attainable, though no less important, standard of quality by producers whose aim is not to obtain pharmaceutical drug approval.

However, regardless of the intent of the study, fundamentally, MCRAA believes researchers must have access to diverse cannabis strains and cannabis derived compounds from sources other than the NIDA-contracted cultivation at the University of Mississippi.

Quality and Safety

MCRAA supports adherence to the highest possible quality standards for cannabis and cannabis-derived compounds consistent with current FDA standards for clinical research, as well as safety standards for trial participants utilizing drugs containing cannabis or cannabis derived compounds in clinical trials.

MCRAA recognizes the importance of quality standards for all FDA regulated drugs, whether those products contain cannabis or cannabis-derived compounds or contain any other substances. Drug sponsors should provide quantitative data regarding the phytochemicals that are present in their proposed product throughout the various stages of manufacturing and a drug development program, including but not limited to cannabinoids, terpenes, and flavonoids.

However, while suggesting cannabis is to be held to essentially the same regulatory standards as any other botanical raw material, botanical drug substance, or botanical drug product, the FDA then indicates that even when the cannabis or cannabis-derived compound is under the threshold of 0.3 % dry weight of THC, that the US Drug Enforcement Agency (DEA) should be consulted, which may result in certain inconsistencies in process.

It is often difficult to establish in-process control strategies that effectively detect and adjust variations. MCRAA believes consistent evaluation is necessary for quality assurance of finished products, which warrants adherence to existing FDA standards for consistency of product and consistency of quality during the investigation of cannabis and cannabis-derived products.

Standardized Processes

If all of the processes for drug development are standardized, a high-quality finished product is produced. In order to assure batch-to-batch consistency, drug researchers and developers have to standardize their processes and inputs to help minimize any potential variation in product. This permits transferable clinical research data and is guaranteed by consistent monitoring.

In addition, while it is certainly important to accurately and effectively measure cannabis and cannabis-derived compounds, derivatives, or extracts of cannabis to ensure that they contain no more than 0.3 percent by dry weight of THC to comply with the Controlled substances Act (CSA) as modified by the 2018 Farm Bill (the Agriculture Improvement Act of 2018, PL 115-334), we believe that the FDA should maintain its regulatory authority over drug development and not unnecessarily relinquish regulatory authority to another federal agency, such as the DEA.

Conclusion

Thank you for the opportunity to comment on the FDA Draft Guidance to Encourage Cannabis Related Clinical Research. While MCRAA appreciates the increased clarity of guidance that this draft provides, we still continue to see a growing dichotomy between how cannabis or cannabis-derived compounds and materials are evaluated and other botanicals for the purpose of clinical research and drug development.

It is important to note that consistency of method and mode of approach for drug development and clinical research is critical for evaluation, as well as drug quality and patient safety.

While legal requirements for THC levels are important and must be maintained and therefore regulated, they should not create further administrative burdens and artificial barriers to the proper clinical evaluation of cannabis and cannabis-derived compounds for drug development.

Sincerely,

Theodore Zanker, MD, DLFAPA, DLFAACAP

Chair, Medical Cannabis Research Advocacy Alliance