Quality of Herbal Drugs – What's New?
Introduction
The field of herbal medicines is evolving constantly due to changes in regulatory requirements, scientific progress and an increased focus on patient safety.
Thus, the European Medicines Agency's (EMA) Committee on Herbal Medicinal Products (HMPC) finalized the revised Guideline on Good Agricultural and Collection Practice (GACP) for herbal starting materials. Furthermore, the HMPC released a draft public statement on Cannabis flos for public consultation until October 2025.
In parallel, the United States Pharmacopeia (USP) and the European Pharmacopoeia (Ph. Eur.) have recently issued several updates relating to the quality requirements for Herbal Drugs and Herbal Drug Preparations. Changes were also made in particular to the Cannabis Flower monographs.
These developments highlight a key topic: The ongoing effort to increase the global harmonization of quality standards for herbal medicinal products (HMPs).
European Medicines Agency (EMA) Updates
Guideline on Good Agricultural and Collection Practice (GACP) of Starting Materials of Herbal Origin
The EMA's HMPC has finalized the revised GACP guideline. The guideline came into effect in August 2006 and it was intended to provide guidance to ensure appropriate and consistent quality of herbal substances and herbal preparations. The recent update reflects technological progress and clarifies regulatory expectations, e.g. considering Annex 7 to the EU GMP Guidelines ("Manufacture of Herbal Medicinal Products") issued in 2009.
Recommendation
4/5 November 2026
Avoiding non-Compliance in Packaging Operations - Live Online Training
Key Revisions
- Distinction between GMP and GACP: Clearer guidance on when activities fall under GACP, GMP part II (APIs), or GMP part I (finished medicinal products). In general, the closer the preparation is to the final product, the stricter the requirements are.
- Indoor Cultivation Provisions: Recognition of the growing role of controlled environment agriculture. Indoor cultivation must define critical quality attributes and process parameters, with a standardized cultivation process and qualified equipment.
- Supply Chain Responsibility: All supply chain actors (e.g., growers, harvesters, collectors, producers, traders, processors of medicinal plants and herbal substances) must maintain proper batch documentation and quality systems and demand that their partners do likewise.
The EMA also published an Overview of comments received on the draft guideline published last year, which was open for comments until 15 July 2024. Moreover, a Q&A document on GMP for herbal extracts used as active pharmaceutical ingredients (APIs) was issued earlier by the EMA. According to the Q&A paper, reference should be made to the table in EU GMP Guide Annex 7 illustrating the application of GACP and GMP (Good Manufacturing Practice). Thus, initial extraction steps in the manufacture of herbal extracts used as APIs should be carried out in compliance with the requirements of EU GMP Part II (see Questions and answers on GMP requirements applicable to the early manufacturing steps for comminuted plants and herbal extracts used as active substances, Reference Number: EMA/INS/GMP/48514/2021).
Draft public statement on Cannabis sativa L., flos
The HMPC published the draft public statement on Cannabis sativa L., flos (EMA/HMPC/69833/2025). The public consultation is open until 31 October 2025.
Are the Requirements for Well-Established or Traditional Use Fulfilled?
To foster a more harmonized approach in the presentation and manufacture of Cannabis-derived medicinal products, the European Commission (EC) requested that the Committee on Herbal Medicinal Products (HMPC) compiles a "Cannabis Glossary" (Compilation of terms and definitions for Cannabis-derived medicinal products, EMA/HMPC/161753/2020) and also suggested exploring the feasibility of establishing an EU herbal monograph on Cannabis sativa L., flos. However, in summary, the HMPC concluded that the requirements for the establishment of an EU herbal monograph on traditional and/or well-established use for herbal medicinal products containing Cannabis sativa L., flos, are (currently) not fulfilled.
European Pharmacopoeia (Ph. Eur.) Updates
Determination of Estragole (New Chapter 2.8.27)
A new European Pharmacopoeia (Ph. Eur.) chapter 2.8.27. Determination of Estragole has been proposed in Pharmeuropa 37.3. The comment deadline was 30 September 2025 (Meanwhile a second new Ph. Eur. chapter 2.8.28. Determination of Thujone has been published in Pharmeuropa 37.4. Comments on the proposed new text for the "Methods in Pharmacognosy" section of the Ph. Eur. are open until 31 December 2025.)
Estragole is a natural organic compound and a constituent of several essential oils. It is suspected to be carcinogenic and genotoxic, as is indicated by a report of EMA's Committee on Herbal Medicinal Products (HMPC) on the use of herbal medicinal products (HMPs) containing estragole (EMA/HMPC/137212/2005 Rev. 1 Corr.). Because of the generally accepted evidence of genotoxic carcinogenicity, exposure to estragole should be kept as low as practically achievable. In the evaluation of HMPs containing estragole EU Member States should take steps to ensure that the public is protected from exposure.
The new Ph. Eur. general chapter is intended for the quantitative estragole determination in herbal drugs and herbal drug preparations. The proposed method (gas chromatography) has been validated for aniseed, anise oil, star anise, star anise oil, sweet fennel, bitter fennel, cut bitter fennel, bitter-fennel fruit oil and bitter-fennel herb oil. However, its suitability for other herbal drugs or herbal drug preparations must be demonstrated, or an alternative validated method must be used.
Cannabis Flower Monograph (Pharmeuropa 37.4)
A revised version of the Ph. Eur. Cannabis Flower Monograph has been published in Pharmeuropa 37.4. The comment deadline is 31 December 2025.
The revised Cannabis Flower Monograph introduces wider acceptance criteria for foreign matter such as seeds and leaves and adjusts identification tests.
Identification Test C (High-performance thin-layer chromatography, HPTLC): The acceptance criterion for the HPTLC zone for delta9-tetrahydrocannabinol (THC) for the THC-dominant type is widened. This is to include cases where this zone may be very faint or even absent. As THC mainly originates from the degradation of the corresponding acid (THCA), THC-dominant types tested shortly after being harvested and dried may contain THC contents that are undetectable by the HPTLC procedure.
Foreign matter: The additional acceptance criteria for seeds and leaves for the herbal drug when prescribed to patients as a medicinal product are widened:
- Max. 2 per cent; if the herbal drug is to be prescribed to patients as a medicinal product, it does not contain any mature seeds.
The current requirement is the following: maximum 2 per cent; if the herbal drug is to be prescribed to patients as a medicinal product, it does not contain any seeds and the whole herbal drug does not contain any leaves more than 1.0 cm in length.
Immature seeds appear to be relatively common in Cannabis Flos in some member states where this herbal drug is prescribed to patients. The presence of leaves more than 1.0 cm in length is also not rare in whole trimmed Cannabis Flower similarly prescribed. However, excessive leaf content (i.e., foreign organs) is already controlled by the general maximum limit of 2 per cent, as set out in the general Ph. Eur. chapter 2.8.2. Foreign Matter.
United States Pharmacopeia (USP) Updates
Cannabis Species Inflorescence Monograph
The USP Herbal Medicines Compendium (HMC) published the final authorized Version 1.0 of its Cannabis Species Inflorescence Monograph.
- Definition: Covers the female inflorescence of Cannabis sativa L. and specifications for related chemotypes (THC-dominant, CBD-dominant, intermediate).
- Labeling Requirements: Products must fall within 90-110% of the labeled total THC and CBD content. Labels must also specify microbial load treatments to aid patient decisionmaking. In cases where the product conforms to the stricter 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.
- Contaminants: Stricter microbial testing limits apply for at-risk populations, like immunocompromised patients, to minimize infection risks from cannabis inhalation. Limits for Heavy Metals include arsenic (max. 0.2 ppm), cadmium (max. 0.3 ppm), lead (max. 0.5 ppm), and mercury (max. 0.1 ppm).
- Loss on Drying (LOD): max. 10.0%
Further specific tests include: Foreign Organic Matter (max. 5% of stems that are 3 mm or more in diameter; max. 2% of any other foreign organic matter), Total Ash (max. 20.0%), and Water Activity (0.60 ± 0.05).
Revision of USP Chapter Articles of Botanical Origin
A revised version of USP chapter Articles of Botanical Origin (ABOs) has been published in the Pharmacopeial Forum (PF) 51(4). The comment deadline was 30 September 2025.
The draft introduces a new GC-MS method for polycyclic aromatic hydrocarbons (PAHs), with limits aligned to EU standards.
- PAHs of Concern: benzo[a]pyrene, chrysene, benz[a]anthracene, and benzo[b]fluoranthene.
- Acceptance Criteria: Benzo[a]pyrene ≤10 ppb; sum of the four PAHs ≤50 ppb.
PAHs are aromatic compounds consisting of two or more fused aromatic rings made up of carbon and hydrogen. They have been extensively studied since it was discovered that some of them are genotoxic and carcinogenic, such as benzo[a]pyrene. Recent studies have shown that some medicinal plants can be contaminated with PAHs, which can arise due to contamination either during the post-harvest processing or by environmental sources. Due to their high surface areas, herbal drugs are susceptible to environmental contamination by PAHs, and drying processes can potentially contribute to this contamination.
Conclusion
The recent updates from the Ph. Eur., USP, and the EMA demonstrate a shared global approach: Herbal medicines are now evaluated not just as "Natural Remedies", but also according to rigorous, science-based pharmaceutical quality standards. Together, these measures ensure that herbal medicinal products meet the high expectations regarding safety, consistency and efficacy, thereby fostering greater trust among healthcare providers, regulators and patients.
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.
