USP´s Quality Considerations for Medical Cannabis

Authors from the USP Cannabis Expert Panel recently published an article entitled "Cannabis Inflorescence for Medical Purposes: USP Considerations for Quality Attributes". The paper was published on April 13, 2020 in the Journal of Natural Products (J. Nat. Prod. 2020, 83, 1334-1351). So far neither a USP Monograph on Cannabis nor a Ph. Eur. Monograph is available. However, there are some national Monographs for Cannabis Flower and Cannabis Extract, for example in the German Pharmacopoeia (Deutsches Arzneibuch, DAB).

Need for Quality Control and for Public Quality Standards

The authors of the article state that recalls due to contamination and incorrect cannabinoid-composition labeling indicate the need for quality control standards. In 2016, USP published a Stimuli article in Pharmacopeial Forum (PF 42.1) on quality standards for medical cannabis. On the basis of public feedback, USP concluded that the development of quality standards for medical cannabis was necessary, but that inclusion of such standards in a legally recognized official compendium (like the USP) was not advisible given the current legal status of cannabis at the U.S. federal level. Therefore, this paper provides analytical methods and specifications

• for the identification of cannabis (specifically, the pistillate or female flower, often referred to as the “bud”) using macroscopic, microscopic, and chromatographic procedures,
• to determine the composition of components using quantitative tests such as high performance liquid chromatography (HPLC) and gas chromatography (GC), 
• to limit the content of common contaminants.

LIMITS FOR CONTAMINANTS

• Pesticide Residues: Pesticide residue levels for oral botanical drugs are controlled through the limits presented in USP general chapter <561>. However, considering the high level of uncertainty that inhalation introduces (and the absence of appropriate toxicological data), a 1000-fold safety factor is suggested, in particular for the limits for suspected pesticides that are not listed in <561> (these pesticides limits are calculated based on ADI levels). 
• Elemental Contaminants:
  • Arsenic: max. 0.2 µg/g
  • Cadmium: max. 0.2 µg/g
  • Lead: max. 0.5 µg/g
  • Mercury: max. 0.1 µg/g
  Microbial Contaminants: According to USP chapters <61> and <62> the authors recommend the following:
  • total aerobic bacteria: max. 10^5 cfu/g
  • total combined molds and yeasts: max. 10^4 cfu/g
  • total bile-tolerant Gram-negative bacteria: max. 10^3 cfu/g
  • absence of Salmonella species and E. coli
  More stringent limits for inhalation products following USP chapter <1111>:
  • total aerobic bacteria: max. 10^2 cfu/g
  • total combined molds and yeasts: max. 10 cfu/g
  • absence of biletolerant Gram-negative bacteria, S. aureus, and P. aeruginosa
  • testing for Aspergillus spp.
• Mycotoxins: max. 20 ppb for the total of aflatoxins B1, B2, G1, and G2 combined and max. 5 ppb of aflatoxin B1.

Decontamination

Reduced microbial loads may be achieved through methods such as ozonation or irradiation. According to the article irradiation of botanical materials is prohibited in the U.S., except on certain species that have been granted an exception. In addition, gamma irradiation can reduce the concentration of some terpenes such as terpinolene.  In cases where irradiation (or other treatments to reduce the microbial load of the finished product) is permitted, testing for microbial contaminants should be done before the treatment.

OTHER QUALITY ATTRIBUTES

• Water Activity: 0.60 ± 0.05. 
• Foreign Organic Matter: max. 5% of stems 3 mm or more in diameter and max. 2% of other foreign matter. 
• Total Ash and Acid-Insoluble Ash: Total ash: max. 20.0%, and acid-insoluble ash max. 4.0%. 
• Packaging and Storage: Store in a cool and dry place in well-closed containers and protected from light and moisture. USP chapter <659> defines "cool conditions" at any temperature between 8 and 15 °C, and a "dry place" to be a place that does not exceed 40% average relative humidity at 20 °C (or the equivalent water vapor pressure at other temperatures).

The paper is published in the April issue of the Journal of Natural Products. Additional information is provided at USP´s Cannabis website including the USP public health position paper, FAQs, and the USP public comments to FDA and USDA.