Drug Regulators, EMEA, Publish Draft Guidance on Genotoxicity Testing for Traditional Herbal Medicinal Products.

Inclusion in the Community list of a herbal substance/preparation represents a significant advantage to applicants seeking registrations for traditional herbal medicinal products. This is because once a herbal substance/preparation is included in the Community list an applicant will not be required to provide evidence of the safe and traditional use of a medicinal product for which he seeks a traditional use registration if he demonstrates that the proposed product and related claims in the application comply with the information contained in the list.

Progress with the development of Community list is being hampered by the absence of genotoxicity data. Experience to date confirms that many well known traditional herbal substances/preparations, already widely available within the Community, will be excluded from the Community list solely as a consequence of absence of genotoxicity data and thus any potential benefits of the list to applicants will be lost.

The stepwise approach described in the guideline sets out a pragmatic approach to address both scientific aspects of genotoxicity testing and the special needs of herbal medicinal products within the current regulatory framework applicable to these products.

Strictly speaking, genotoxicity testing should be carried out by individual applicants on their specific materials and it is recognised that this represents a major task and considerable duplication of effort particularly for applicants seeking registrations for traditional herbal medicinal products. Industry has therefore been encouraged to consider undertaking collaborative research on genotoxicity and one such study is underway within some Member States.

This guidance offers a strategy to reduce the number of test materials such that a representative range of herbal preparations is tested rather than requiring individual manufacturers to undertake their own testing on specific preparations.

Scope

This guideline addresses the selection of materials for genotoxicity testing in support of applications for traditional herbal medicinal products/ herbal medicinal products.

This guideline provides possible approaches to what types of materials should be subjected to testing for genotoxicity bearing in mind that different herbal preparations may have different toxicological profiles.

The main objective is to achieve consensus on a standard range of test materials which could be considered representative of the commonly used herbal substances/preparations with the intention of facilitating entry to the Community list.

Selection of Materials for Genotoxicty Testing

The concept of applying a reduced design approach such as ‘bracketing/ matrixing’to the selection of samples for genotoxicity testing is proposed. Using the ‘bracketing’ concept, only samples on the extremes of certain design factors would be tested. The reduced design assumes that the genotoxic potential of any intermediate preparation is represented by the test results of the extremes tested. Where a reduced testing design is proposed, evidence (usually chromatographic data) should be provided to demonstrate that the samples to be tested represent the phytochemical profile of all materials to be covered by the genotoxicity testing.

Herbal Substance Used in Herbal Medicinal Products

Where the entire herbal substance is incorporated directly into the herbal medicinal product, e.g. in capsules, tablets, the test material for genotoxicity testing, should, in theory, cover the entire spectrum of phytochemical constituents, including polar and non-polar constituents. Test materials for genotoxicity testing should therefore include extraction solvents which encompass the entire phytochemical profile. The choice of solvents should be justified. Consideration should be given to including an extract mid-range e.g. 50% water.

Fixed oils/essential oils/extracted juices etc

Where the herbal preparations include for example fixed oils, essential oils, expressed juices etc these should be addressed on a case by case basis. Some materials may need to be tested individually as part of the genotoxicity test programme. In the case of expressed juices, it may be possible to demonstrate that the material is covered by testing of, for example, an aqueous extract.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com