New Quality Standards for Medical Cannabis and CBD
Introduction
The United States Pharmacopeia (USP) and the European Pharmacopoeia (Ph. Eur.) have recently issued several (draft) monographs for cannabis flower and cannabidiol (CBD), incorporating quality standards and testing procedures. These new standards aim to enhance the safety, consistency, and quality of cannabis products used for medical purposes. The monographs address various aspects, such as acceptable ranges for active components, microbial contaminant limits, impurity testing, and labelling requirements. This article summarizes some of the recent updates.
European Pharmacopoeia (Ph. Eur.) Monographs
The Ph. Eur. introduced new monographs for Cannabis Flower and Cannabidiol, effective July 2024. It is therefore expected that the Ph. Eur. Cannabis flower monograph will replace the currently existing national monographs in countries like the Netherlands, Denmark, Germany, and Switzerland. The monograph covers raw materials (for example for the preparation of extracts) and canna bis prescribed as a medicinal product, including stricter contaminant limits for inhalation products to reduce patient risk.
For cannabis flower products, heavy metal limits (Pb, As, Cd, Hg) are significantly lower than those provided in the general Ph. Eur. monograph Herbal Drugs, reflecting the risks associated with inhalation. Compared to the draft version published in 2022 (Pharmeuropa 34.4), additional requirements have been included for the content limits, in the production section and on the tests for foreign matter. If the herbal drug is to be prescribed to patients, it does not contain any seeds. However, regarding other contaminants like, for example, mycotoxins, pesticides and microbial contaminants (i.e., according to Ph. Eur. 5.1.8 or 5.1.4, depending on the route of administration), it is still necessary to refer to the general Ph. Eur. monograph Herbal Drugs. The Loss on drying (LOD) limit has been set to max. 12.0 % (in the draft version max. 10.0% was proposed).
In addition, the final Ph. Eur. Cannabidiol monograph now clearly defines that Ph. Eur. CBD is isolated from the Cannabis sativa L. plant. This is different compared to the draft version published in 2022 (Pharmeuropa 34.3) where it was proposed to define that "CBD is isolated from natural sources".
United States Pharmacopeia (USP) Draft Monographs
The USP Herbal Medicines Compendium (HMC) released a revised draft Monograph for Cannabis Species Inflorescence in April 2024, replacing the 2023 draft. Key updates include adjustment of the acceptable content range for tetrahydrocannabinol (THC) and cannabidiol (CBD) from 80-120% to 90-110% to align with medical use standards. The new monograph also offers two options for microbial contaminant testing. One uses standard limits, while the other provides stricter limits for at-risk populations, like immunocompromised patients, to minimize infection risks from cannabis inhalation:
- Option 1: Total aerobic bacterial count limit of 105 CFU/g, total yeast and mold count of 104 CFU/g, and a limit of 103 CFU/g for bile-tolerant Gram-negative bacteria + absence of specified microorganisms.
- Option 2: Stricter limits for at-risk populations, with a total aerobic bacterial count of 102 CFU/g and yeast and mold count of 101 CFU/g + absence of specified microorganisms using methods from USP chapters <1111> and <62>
Recommendation
5/6 November 2025
Ph. Eur., USP and other Pharmacopoeias - Live Online Training
In addition, the USP proposed a revised draft for a new monograph for cannabidiol (CBD), focusing on CBD derived from natural sources rather than synthetic production methods (Pharmacopeial Forum (PF) 50.3). Compared to the previous version published in PF 48.1 (2022), significant changes include new testing methods for organic impurities, a new liquid chromatography procedure, and stricter water content limits (the water content limit has been reduced from previously proposed 1.0% to 0.3% per USP <921>). CBD obtained from synthetic routes of production could result in different impurity profiles. The revised proposal does not include specifications for such synthetically derived CBD. Synthetic impurities (e.g., Olivetol, 4-Monobromo-CBD) could be used to differentiate the naturally derived CBD from synthetically derived CBD. However, the corresponding tests are no longer included in the tests for organic impurities.
Moreover, the USP published a further draft chapter last year in Pharmacopeial Forum (PF) 49.3: <1568> Quality Considerations for Cannabis and Cannabis-Derived Products for Clinical Research. The Appendix of the proposed new USP chapter <1568> provides useful pictures of the following:
- Macroscopic and microscopic characteristics of Cannabis flower,
- HPTLC / HPLC and GC profiles of cannabinoids,
- Fingerprints of the three cannabis chemotypes before and after decarboxylation,
- Commonly observed dominant and co-dominant terpenes in commercial Cannabis flower.
FDA Study on Elemental Impurities in Cannabis Vapors
Following the previously published article on microbial contamination (see Investigation of microorganisms in cannabis after heating in a commercial vaporizer, in Frontiers in Cellular and Infection Microbiology, 13 January 2023, Volume 12 - 2022), authors from the FDA recently published an article on elemental impurities in cannabis following vaporization. The experimental study evaluated a single vaporizer and three cannabis plant materials, to assess whether a transfer of heavy metals from cannabis material to cannabis vapor occurs during the vaporization process under the applied study conditions. The study concluded that elemental impurities such as lead, arsenic, cadmium, and mercury do not significantly transfer from cannabis to vapor under standard heating conditions.
However, these impurities may transfer at higher temperatures or with prolonged heating, indicating that further research is necessary to confirm safety across different usage levels (see Analysis of elemental impurities in cannabis following vaporization, in Talanta Open, Volume 9, 2024).
Recommendation
29/30 April 2025
GMP and Quality Requirements for Radiopharmaceuticals - Live Online Training
Storage and Labelling
The Ph. Eur. Monograph Cannabis flower defines that the flowers have to be stored in an airtight container. The label states the percentage contents of total THC and total CBD. In addition, the label states if the herbal drug is to be prescribed to patients as a medicinal product.
Moreover, the USP HMC draft Monograph (Cannabis Species Inflorescence) prescribes the following: Store in a cool and dry place in well-closed containers and protected from light and moisture. Water activity during storage should be maintained at 0.60 ± 0.05. The USP chapter <659> defines cool conditions as any temperature between 8° and 15° and a dry place as a place that does not exceed 40% average relative humidity at 20° or the equivalent water vapor pressure at other temperatures". However, an article for which storage in a cool place is directed may, alternatively, be stored and shipped as refrigerated (e.g. in a cooling box), unless otherwise specified by the individual monograph.
According to the USP the label states the following:
- The name of the article as Cannabis Species Inflorescence and the scientific Latin binomial as Cannabis sativa L.
- The amount of the total THC-related constituents (THCA, Δ9- THC) and the amount of the total CBD-related constituents (CBD, CBDA), in mg/g. The label also indicates whether the cultivar is the THC-dominant, CBD-dominant, or THC/CBD intermediate chemotype.
- The method used for Content of Cannabinoids (if the proposed Procedure 1 is not used).
- Any other cannabinoids present above 10 mg/g.
The label also indicates whether the article has been treated to reduce the microbial load and the method used. In cases where the product conforms to limits for inhaled use, and in order to aid at risk populations in choosing lower-risk products, the label should identify the product as having a reduced microbial load.
Implications and Next Steps
Stakeholders are encouraged to provide input on the revised USP proposals, especially regarding microbial limits, impurity profiles, and content specifications. The updates reflect an effort to ensure cannabis products meet regulatory requirements, particularly for medical use. Moreover, the revisions aim to align cannabis quality standards with those for other herbal pharmaceuticals, supporting safe and effective use. With a view to simplifying the global distribution of medicinal cannabis, harmonisation of the pharmacopoeia monographs presented would be desirable.
About the Author
Dr Andrea Kühn-Hebecker is Operations Director and organises and conducts courses and conferences on behalf of the ECA Academy in the area packaging, herbal medicinal products, development and Lifecycle Management.
