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Performance and data interpretation of the in vivo comet assay in pharmaceutical industry: EFPIA survey results

Plappert Helbig, Ulla, Van der Leede, Bas-jan, Doherty, Ann, Guérard, Melanie , Howe, Jonathan and Thybaud, Véronique (2014) Performance and data interpretation of the in vivo comet assay in pharmaceutical industry: EFPIA survey results. Current Topics in Genotoxicity Testing of Mutation Research – Genetic Toxicology and Environmental Mutagenesis, 775–77. pp. 81-88.


This paper summarizes a survey suggested by the Safety Working Party of European Medicines Agency (EMA), and conducted by the European Federation of Pharmaceutical Industries and Associations (EFPIA) to investigate experience accumulated in European pharmaceutical companies with the conduct of the in vivo comet assay for regulatory purpose. The objective was to evaluate better the details of results obtained, and to identify potential on difficulties encountered with the interpretation of study data. In total 147 studies have been conducted (in-house or outsourced) and the conclusion on the comet assay response was shared for 136 studies. Most of the studies were negative (118/136). Only about 10% (14/136 studies) of the comet assays showed a positive response. None of the positive comet assay results were clearly associated with organ toxicity indicating that the positive responses are not due to cytotoxic effects of the compound in the tissue examined. The number of comet assays with an equivocal or inconclusive response are rare, respectively <1% (1/147 studies) and 2% (3/147 studies). In case additional information (e.g. repeat assay, organ toxicity, metabolism, tissue exposure) would have been available for evaluation, a final conclusion could most probably have been drawn for most of these studies. All negative in vivo comet assays that were submitted in conjunction with a negative in vivo micronucleus assay (46/97) were accepted by the regulatory authorities to mitigate a positive in vitro mammalian cell assay following the current ICH S2 guidance. The survey results demonstrate the robustness of the comet and the regulatory acceptance of the current ICH S2 guidance.

Item Type: Article
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13


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