Challenges of safety evaluation.

Each application for authorisation of a medicinal product must be accompanied by the particulars and documents referred to in Directive 2001/83/EC on the Community code relating to medicinal products for human use. Details on the documentation needed for traditional herbal medicinal products (THMP) are given in article 16c of the above mentioned Directive. It is pointed out that a bibliographic review of safety data together with an expert report and additional data, if necessary, are required. The Committee on Herbal Medicinal Products (HMPC) provides in its "Guideline on the use of the CTD format in the preparation of a registration application for traditional herbal medicinal products" (EMA/HMPC/71049/2007 Rev. 1) guidance on how to present the information and the dossier needed for an application. There, in agreement with the Directive 2001/83/EC, a bibliographical review of safety data is required within the "Non-clinical Overview". However, it is assumable that for such products, with a long tradition of usage bibliographical information relating to non-clinical safety are available, even if incomplete or not in accordance with today׳s state of the art. In 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) it is reflected how to deal with such an incomplete set of data for traditional herbal medicinal products and crucial information are highlighted. This article will focus on the explanation of the requirements needed for the non-clinical safety evaluation of THMPs and some detailed explanations of the performance and interpretation of the mutagenicity studies.