- Annex 7 of EudraLex Volume 4, titled Manufacture of Herbal Medicinal Products, provides specific Good Manufacturing Practice (GMP) guidance for the production of herbal medicinal products intended for human use. Herbal medicinal products include plant-derived substances—such as dried herbs, herbal preparations, and finished products—that are used for therapeutic purposes. Due to the natural variability of plant materials and the complex composition of herbal substances, Annex 7 introduces additional GMP considerations beyond standard pharmaceutical requirements to ensure consistent quality, safety, and efficacy.
- A major focus of Annex 7 is the quality and control of starting materials, specifically herbal substances and preparations. These materials, often derived from cultivated or wild-harvested plants, are inherently variable in their chemical composition due to factors such as species differences, geographical origin, harvesting time, and processing methods. As a result, manufacturers are expected to implement rigorous specifications, testing, and identity verification procedures for herbal raw materials. This includes confirmation of botanical identity using macroscopic, microscopic, and chemical analyses, and controls to detect contamination with pesticides, heavy metals, microbial agents, and foreign matter.
- Annex 7 also addresses the qualification of suppliers and traceability of herbal materials. Since herbal substances often come from non-pharmaceutical sources (e.g. agricultural or wild harvesters), manufacturers must ensure that suppliers adhere to Good Agricultural and Collection Practices (GACP). Documentation of the plant’s origin, handling, and storage conditions is crucial for maintaining the integrity and traceability of the material throughout the supply chain. The annex emphasizes the importance of maintaining a herbal drug master file or equivalent documentation to ensure control from field to finished product.
- The annex outlines expectations for processing of herbal substances into herbal preparations, which may involve drying, extraction, purification, distillation, or concentration. These steps must be carefully controlled and validated to ensure batch-to-batch consistency, even when the active constituents are not fully identified. In such cases, the “marker compound” approach may be used to monitor and control the manufacturing process by selecting indicative constituents that reflect quality and stability.
- Another critical aspect of Annex 7 is the management of environmental and microbial contamination, particularly because herbal products may contain naturally occurring microbial flora. Drying, milling, and extraction processes must be controlled to reduce contamination and prevent degradation. For products intended for internal use, particularly sterile herbal medicines, the use of validated microbial reduction or sterilization techniques is required, while ensuring the integrity of the active constituents.
- Packaging, labeling, and stability requirements are also emphasized. Packaging materials must protect the herbal product from moisture, light, and oxidation, which can degrade the product over time. Labeling must include precise information on plant species, part used, quantity, and preparation method to ensure transparency and compliance. Stability testing should consider the complex and sometimes unstable nature of herbal constituents, with appropriate justification for shelf life and storage conditions.
- Finally, personnel training and documentation are highlighted as essential components of herbal GMP. Personnel must be trained not only in GMP but also in botany, pharmacognosy, or related fields to adequately assess plant materials. Batch documentation should provide full traceability, including the origin and quality of raw materials, the manufacturing process, and the quality control tests performed.
- In summary, EudraLex Volume 4 – Annex 7 offers tailored GMP guidance for the manufacture of herbal medicinal products, accounting for their natural origin, biological complexity, and potential for variability. It reinforces the need for thorough control of raw materials, careful processing, and robust quality assurance systems to deliver safe, effective, and reproducible herbal medicines. By bridging the gap between traditional medicine and modern pharmaceutical standards, Annex 7 supports the integration of herbal therapies into regulated healthcare systems across the European Union.
Further reading:
- EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines
- EudraLex – The Rules Governing Medicinal Products in the European Union, Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use Annex 7: Manufacture of Herbal Medicinal Products
