Abstract
In recent years, to reduce animal testing international harmonization of technical requirements has been promoted without compromising safety and efficacy, and ICH S5 guideline on reproductive toxicology: -Detection of reproductive and developmental toxicity for human pharmaceuticals- was revised . In ICH S5 (R3) guideline, the conditions under which alternative methods can be used to assess embryo-fetal developmental toxicity are described in an Annex, allowing the use of alternative methods as part of developmental toxicity testing in drug safety assessment. The zebrafish model has been recognized as a powerful tool to predict the teratogenic potential and it have been used to screen drugs in an early stage. Our current study was conducted with a view to using the method for regulatory purposes in zebrafish. At four participating laboratories (Astellas Pharma Inc., BoZo Research Center Inc., Maruho Co., Ltd., Mitsubishi Chemical Research Corporation), we used 29 ICH-positive and 3 ICH-negative compounds and evaluated the predictive capacity of the test method. This project is the first consortium research for the zebrafish teratogenicity assay in Japan. We will share the standardized protocol for the zebrafish teratogenicity assay, which showed that test results were fairly interlaboratory reproducibility and share results of the concordance between zebrafish and in vivo (rat and rabbit) teratogenicity data.
