Comment to the Draft Guideline on the Assessment of Genotoxic Constituents in Herbal Substances /
Preparations held by the EMA – European Medicinals Agency in 2008 (EMEA/HMPC/107079/2007)

By Dr. Mathias Schmidt, Leader of the Scientific Board (ANME)


The proposed guideline on the assessment of genotoxic constituents in herbal substances and herbal preparations may, if applied the way it is proposed, constitute a very high burden for the sector of traditional herbal medicinal products.

The guideline is based on the assumption that generally the absence of a hazard cannot be demonstrated by long-term experience, thus every single plant is suspicious until proven non-genotoxic with adequate experimental data. However, the requirement for genotoxicity testing should not be based on hypothetical considerations, but be restricted to cases where there is a reason for concern, either through observations related to the use of the preparation, or, in some cases, through data related to relevant constituents of the herbal substance, herbal preparation or combinations therefrom.

Even in cases where the decision is taken to undergo genotoxicity testing, the described sequence may not be adequate. As mentioned in the guideline, phytochemicals such as quercetin, but also many flavonoids give false-positive results in the AMES test. In cases where the necessity to proceed to step 2 can already be expected from the content of flavonoids, the mandatory testing in step 1 may be considered useless. Regulatory options should be introduced for such cases, allowing to start testing at a later step of the testing sequence.

It is suggested that results obtained with a combination preparation should be acceptable without the need of testing the individual combination partners. It is also suggested that in cases where there are already existing results for the individual components of a preparation, no further testing should be required for the combination.

In the following, some passages of the guideline are commented in more details:

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