Views: 0 Author: Site Editor Publish Time: 2023-02-01 Origin: Site
On January 23, 2023, the FDA issued final guidance, "Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research." The FDA issued a draft guidance earlier in July 2020 and received 60 public comments. This release is the final guidance.
The guidance outlines current recommendations for the use of cannabis and cannabis-derived compounds in clinical research for human medicines in drug development. Cannabis and cannabis-derived compounds include botanical raw materials, extracts, and highly purified substances of botanical origin. Those involved in clinical research on cannabis can rely on this FDA guidance for information on recommended sources of cannabis for clinical research, as well as quality and control status to consider.
On January 23, 2023, the FDA published new guidance titled "Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research." This non-binding guidance discusses three key cannabis-related topics:
How to source cannabis for clinical research;
How to calculate the percentage of delta-9 tetrahydrocannabinol (THC) throughout the study period;
General quality considerations for the development of human medicinal products containing cannabis and cannabis-derived compounds.
Generally, to be considered "industrial hemp," a product must contain less than 0.3 percent delta-9 THC. Anything over 0.3% delta-9 THC is considered marijuana, a Schedule I controlled substance. Human medicines containing hemp, cannabis, and cannabis-derived compounds are generally subject to the same authorities and requirements, including quality standards, as FDA-regulated pharmaceutical products containing any other substance.
The goal of the FDA's latest guidance is to support clinical research in the development of cannabis and cannabis-derived human medicines. The guidance does not address the development of synthetic cannabinoids, nor does it cover other FDA-regulated products.
For many years, the National Institute on Drug Abuse (NIDA) drug supply program was the only legal source of cannabis for scientists and for clinical studies above the 0.3% delta-9 THC threshold. In 2020, the Drug Enforcement Administration (DEA) adopted new procedures to allow new manufacturers to register to grow, grow, cultivate or harvest marijuana. However, there is confusion as to whether these newer manufacturers' products can be used in clinical studies. This guidance seeks to clarify this confusion and states that:
For cannabis that exceeds the 0.3% delta-9 THC threshold and is not subject to an Investigational New Drug (IND) application, supplemental sources of Schedule I cannabis material available for research can be provided using the NIDA Drug Supply Program and DEA authorization.
For any cannabis source (above or below the 0.3% threshold) applied as an IND, it can be used upon application approval.
Procurement for cannabis clinical research has been an obvious area of concern for participants, and the FDA has also provided guidance on more nuanced issues facing the industry.
As part of any drug IND, investigators must submit sufficient information at each stage of clinical research to demonstrate the drug's identity, quality, purity, and potency. The guidance includes additional principles and recommendations of particular relevance to the development of medicines containing cannabis and cannabis-derived compounds:
Cannabis and cannabis-derived compounds are subject to the same regulatory standards as any other botanical raw material, botanical drug substance, or botanical drug product. This includes ensuring batch-to-batch consistency, performing microbiological examination and sterility testing, and testing of raw materials (and other specific requirements on page 6 of the guidance).
Dosage form specific quality testing should be performed.
Impurities of natural compounds should be controlled.
Researchers should not rely on published literature as a substitute for data from a full toxicology program to support drug product development in phase 3 clinical studies (and beyond). Because the specific botanical products reviewed may differ from published studies.
Early evaluation focuses on how cannabinoids are metabolized in the human body to ensure safety. Special toxicology studies on 7-COOH-CBD, the main human metabolite of cannabidiol, are especially recommended.
When drug developers submit INDs to FDA for clinical studies of cannabis-related human drugs, the potential controlled substance status of botanical raw materials, drugs, and drug products should be determined by considering delta-9 THC content. The agency encourages companies to calculate the delta-9 THC content of proposed test products early in drug development and to consult with the DEA to determine the abuse potential and control status of their products. The guidance also discusses optimal calculation methods in the clinical research lifecycle.
Typically, the percent delta-9 THC in a plant material is calculated (the amount of delta-9 THC (and THCA) naturally present in a material sample relative to the dry weight of the sample) prior to extraction or other manufacturing steps. For intermediates or finished products containing cannabis or cannabis-derived compounds, drug developers should use the formulation ingredients and the amount of water removed (including water contained in excipients) to calculate the total delta-9 THC percentage. These calculations should not be used for other purposes (eg, chemical manufacturing and control (CMC)).
FDA may be concerned about liability for drug abuse. FDA may conduct abuse potential assessments as part of the agency's review of new drug applications. This evaluation may affect drug labeling and DEA planning or rescheduling.
The guidance provides FDA's thinking on developing drugs that contain cannabis and cannabis-derived compounds. The FDA said the agency is committed to supporting a wealth of scientific research to understand the therapeutic use and safety of cannabis products. FDA believes that the drug development and review process represents the means to ensure safe, effective, high-quality new drugs, including those containing cannabis and its derivatives.
This FDA guidance helps provide the cannabis industry with clarity on cannabis and cannabis-derived drug development following Congress’ passage of the Medical Cannabis and CBD Research Expansion Act. Stakeholders have been eagerly awaiting updates from the FDA and other federal agencies on the sale and marketing of cannabis-derived products, as well as a scientific review of cannabis, to help with the timeline for reevaluating the substance under the Controlled Substances Act. As a high priority for the Biden administration, we are likely to see a number of key regulatory updates for marijuana in 2023.
The FDA remains cautious about the use of hemp CBD products as food and dietary supplements. The FDA believes that the existing regulatory framework for food and supplements provides "limited tools" to mitigate the risks associated with CBD products and appeals to Congress. Create new rules for the market. The agency also rejected three petitions from advocacy groups asking the agency to allow products containing cannabis to be sold as dietary supplements.
Related Links:
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cannabis-and-cannabis-derived-compounds-quality-considerations-clinical-research-guidance-industry
