Draft Reflection Paper on Drug Interactions of Herbal Medicinal Products

The European Medicines Agency (EMA) has published a "Draft reflection paper on the investigation of drug interactions of herbal medicinal products" (EMA/HMPC/362638/2025). It was adopted by the Committee on Herbal Medicinal Products (HMPC) for release on 24 September 2026. The public consultation has been open since 15 October 2026.

The draft addresses a gap that the ICH M12 guideline leaves open. Herbal medicinal products consist of complex mixtures of phytochemical constituents, and their interaction potential cannot readily be extrapolated from other products. The paper shows how interactions can be evaluated depending on the regulatory basis: Article 8(3), Article 10a well-established use (WEU), or Article 16a traditional use (TU) of Directive 2001/83/EC.

The document is structured in four chapters:

• Introduction,
• Discussion,
• Conclusion,
• References.

The Discussion contains recommendations on data sourcing, data evaluation and product information. A figure summarises the paths for the general collection of relevant DDI data.

The paper focuses on three key questions:

• Which data sources should be considered, from literature on preparations with the same herbal substance through to post-marketing experience?
• Which in vitro and clinical studies are useful, and how can the study design and the choice of substrates be justified?
• How are the results translated into product information, in particular into Section 4.5 and Section 5.2 of the Summary of Product Characteristics (SmPC), and, where relevant, into the cross-references to Sections 4.2, 4.3 or 4.4?

Comments can be submitted until 15 January 2027.

The draft document (PDF) and the comments template are available on the EMA website.