AMES tests

Legislator requires proof of safety

Also for herbal medicinal products, the safety must be proven in toxicity studies during the marketing authorisation procedure. With regard to a possible genotoxic effect in herbal preparations, legal framework conditions and standardised measurement models apply. They are summarized by Kooperation Phytopharmaka in the following article. In addition, Kooperation Phytopharmaka offers to directly purchase individual data on selected plant extracts for the AMES test model.

Risk assessment using AMES tests

In the context of drug development, pharmaceutical companies are required to carry out a risk assessment of the occurrence of potentially genotoxic impurities in the medicinal produc. In the case of herbal medicinal products, the extract or a powdered herbal drug is the active substance. Regarding combination products, evidence of the absence of a genotoxic potential must be provided for each individual active substance. This is regulated in the 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.2). According to this, in Module 2.4, an expert report on the safety assessment of the non-clinical data must be submitted. It is recommended to apply the Guideline on non-clinical documentation in applications for marketing authorisation/ registration applications of well-established and traditional herbal medicinal products (EMEA/HMPC/32116/2005). In particular, reference is made to the following two guidelines for herbal products:

• Guideline on the assessment of genotoxicity of herbal substances/preparations (EMEA/HMPC/107079/2007)
• Guideline on the selection of test materials for genotoxicity testing for traditional herbal medicinal products/herbal medicinal products (EMEA/HMPC/67644/2009)

In the Guideline on the assessment of the genotoxicity of herbal substances/preparations (EMEA/HMPC/107079/2007), the HMPC has described a step-by-step approach to genotoxicity testing. According to this, the AMES test (in vitro) is a sufficient basis for the assessment of genotoxicity if the result is clearly negative. The following guideline must be observed for implementation: OECD Guidelines for the Testing of Chemicals, Section 4 | OECD

Procedure in the event of positive AMES tests

If there is an inconclusive test result, individual substances are often the cause, which lead the AMES in vitro test to a false positive result. This can be excluded on the basis of tests according to two further documents or traced back to the test extract without any doubt:

• Test No. 487: In Vitro Mammalian Cell Micronucleus Test (EN)
• Test No. 474: Mammalian Erythrocyte Micronucleus Test (EN)

Order AMES test results

In recent years, Kooperation Phytopharmaka has acquired or commissioned around 120 AMES tests (in accordance with Directive 2000/32/EC, Method B.13/14 and OECD Guideline 471). Individual reports can be purchased from the database. Note: Please check in advance whether the characteristics of the test extract (extraction solvent, DER range) fit your product and please contact our office.