Aim. This thesis aimed at evaluating the impact of the S2 guideline revision on genotoxicity of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) on the frequency of irrelevant positive in vitro mammalian cell assays and the number of follow-up tests needed.

Methods.  Data on genotoxicity tests submitted between 1998 and 2020 within centralised procedures available at the Federal Institute for Drugs and Medical Devices (BfArM) were analysed regarding their frequency and outcome of the in vitro and in vivo assays.  The guideline versions were compared regarding the frequency of positive in vitro mammalian cell tests, the overall number of in vivo tests and the number of additional in vivo tests to follow up positive in vitro results in the mammalian cell assays.

Results.  The data set of this work included 986 genotoxicity tests comprising of 578 in vitro mammalian cell tests and 408 in vivo tests. Tests came from 275 drug products with 413 different compounds.  56 compounds (13.6 %) of the data set were analysed under the revised guideline version ICH S2(R1), whereas 357 compounds (86.4 %) were tested in accordance with the previous guidelines ICH S2A and S2B. All compounds were tested under option 1 of the standard battery. Within the data set of this work there was no statistically significant decrease of positive in vitro mammalian cell assays under the revised guideline.  Moreover, no decrease in the number of follow-up tests or change in in vivo testing was observed.

Conclusion.  Due to the small data set for the revised guideline ICH S2(R1), only preliminary conclusions can be drawn.  So far, no decrease in the number of irrelevant positive in vitro mammalian cell tests was detectable.