In vitro genotoxicity test package of antibiotics for human use submitted to the Japanese regulatory agency during 2004–2015

The Ames test is used for the mutagenic assessment of drugs; however, it may not provide an accurate genotoxic profile for bactericidal compounds. This study was performed to clarify 1) whether the total number of genotoxicity assays performed (#Assays) was greater during antibiotic development than during the development of other drugs, particularly antivirals, possibly due to the requirement for additional assessments, 2) whether the maximum doses of the Ames test were less when an alternative assay had been performed for antibiotics, and 3) whether some particular alternative assay had an advantage to minimize #Assays in the last decade. Genotoxicity data submitted to the Pharmaceuticals and Medical Devices Agency in Japan during 2004–2015 were used. The #Assays was greater and the maximum doses of the Ames tests were lower for antibiotics, which was more obvious when alternative mutagenic assays had been performed. The mouse lymphoma assay or hypoxanthine-guanine phosphoribosyl transferase gene mutation assay was performed preferentially as an alternative. For antibiotic development, preferred genotoxicity test packages should be discussed in the future for a better understanding of the genotoxic potential of antibiotics.