Testing strategies for preclinical safety assessment of herbal medicinal products: considerations for a pragmatic approach

Introduction: Herbs have been the most important source for medicines during the history of mankind. For registration or authorization as herbal medicinal products (HMPs), this long-lasting and widespread use is, besides data on pharmaceutical and safety aspects and, as far as available, on data from systematic studies on efficacy, part of the assessment. Considerations are necessary on how to apply a pragmatic approach to all these aspects.

Current situation and outlook: Herbal-specific regulatory guidelines are the core of the regulation in this field. They have to define a framework how to use the gathered and documented experience as the main basis in the non-clinical safety assessment of HMPs. In the EU, in accordance with the “Guideline on Non-Clinical Documentation for Herbal Medicinal Products in Applications for Marketing Authorisation (Bibliographical and Mixed Applications) and in Applications for Simplified Registration” (EMEA/HMPC/32116/2005), specialized guidelines provide, for some aspects of this assessment, a framework for a pragmatic way of an adequate inclusion of the long-term use of traditional herbal medicines, while the regulatory situation and safety assessment may be different in case of those herbal substances previously not in medicinal or nutritional use and resemble more to that of new chemical entities. The HMPC Guidelines on the assessment of genotoxicity of herbal substances/preparation and on the selection of respective test materials are examples for such rules.

For other aspects, like the inclusion of the impact of nutritional intake of herbs and phytochemical constituents into the safety assessment, the safety of herbal preparation in sensitive population groups like children, pregnant and lactating women and the elderly, approaches taking the special situation of HMPs into account still have to be improved. The use of e.g. epidemiological data, which has been addressed by the HMPC with respect to children in a particular reflection paper and also by Kooperation Phytopharmaka by its PhytoVis project, will have to find an adequate place within the assessment strategies. Another problem is the fact, that the existing guidance is often not suitable for the assessment of herbals, despite the activities of e.g. the WHO in that field. This can be addressed by a pragmatic approach.

Conclusion: While some aspects of the specific regulatory assessment of HMPs, like the assessment of genotoxicity, have been successfully addressed within the EU by specific guidelines, a pragmatic approach is still needed for other aspects taking into account the specific characteristics of HMPs.