This is done through in vitro, in vivo, qualitative and quantitative assessments of metabolites in different set ups depending on which phase the project is heading. Although there is a general approach based on guidelines, all approaches are project dependent. MetaSafe plays an important role, helping customers to understand prerequisites of their projects. Together with the customers we find out the most pragmatic approach to evaluate, at different phases, the risk for MIST issues and how to continue to increase the confidence of such evaluations step by step.