USP Publishes Draft on Quality Requirements for Cannabis

The USP previously announced the Chapter Elaboration on Quality Considerations for Cannabis. Now the draft for <1568> Quality Considerations for Cannabis and Cannabis-Derived Products for Clinical Research (together with a draft for Dronabinol Capsules) has been published in PF 49.3. Comments can be sent to the USP until end of July.

Background

Due to the growing interest in the use of Cannabis flower for medical purposes quality attributes are needed. Thus, the Ph. Eur., the USP and the FDA recently published the following guidelines and pharmacopoeial monographs:

• FDA's Guidance on Quality Considerations for Clinical Research with Cannabis
• Ph. Eur. Cannabis Monograph (draft)
• USP HMC Cannabis Monograph (draft)
• Ph. Eur. Monograph for CBD (draft)
• USP Monograph for CBD (draft)

USP's Proposal

As cannabis is a heterogeneous matrix, appropriate sampling procedures, as well as tests, analytical procedures, and acceptance criteria to define the identity, content of constituents (e.g., cannabinoids), and limits for contaminants are required. According to the USP, three main cannabis chemotypes have been identified as useful for labeling based on the following cannabinoid constituents:

• Tetrahydrocannabinol (THC)-dominant
• THC / CBD (Cannabidiol) intermediate   
• CBD-dominant

Cannabis plants in each of these chemotypes could be further sub-categorized based on the content of other cannabinoids and/or terpene profiles. In addition, morphologic and chromatographic tests are provided for the identification and quantitative determination of critical constituents.

Water Activity

Limits for loss on drying (LOD) and correction of cannabinoid content for moisture content are not included in the proposal, to avoid potential inflation of cannabinoid content expression by dry weight. In order to control the water available to microbes in the Cannabis flower to prevent microbial growth, the water activity should be controlled at 0.60 ± 0.05.

Contaminants

Limits for contaminants (e.g., pesticide residues, microbial contaminants, mycotoxins, and elemental impurities) are presented based on toxicological considerations and aligned with the existing USP procedures for general tests and assays. Considering the potential inhalation use of Cannabis, the following acceptance criteria for heavy metals are proposed:

• Arsenic: max.0.2 ppm
• Cadmium: max. 0.2 ppm
• Lead: max. 0.5 ppm
• Mercury: max. 0.1 ppm

Moreover, the Appendix of the proposed USP chapter provides useful photos of the following:

• Macroscopic and microscopic characteristics of Cannabis flower,
• HPTLC / HPLC profiles of cannabinoids,
• Fingerprints of the three cannabis chemotypes before and after decarboxylation,
• Commonly observed dominant and co-dominant terpenes in commercial Cannabis flower (the figure shows the dominance and co-dominance of terpenes and that humulene, ocimene, linalool, and ß-pinene are not dominant terpenes).

The proposed USP chapter <1568> Quality Considerations for Cannabis and Cannabis-Derived Products for Clinical Research is available after registration to the Pharmacopeial Forum.