Safety and drug metabolism: Toward nce and first in human

The attrition rate of new chemical entities (NCEs) for central nervous system (CNS) drugs is relatively high, making the development of new CNS drugs a challenge. A significant cause of this is related to safety issues arising either during animal toxicity testing or in the human clinical test phases. To reduce these, and increase approval rates by regulatory agencies, including sophisticated human-cell-based experimental models, e.g. organoids or stem-cells based models, in safety testing strategy of potential candidate drugs will result in an improved understanding and prevent safety issues in humans. Especially when these approaches are combined with omics tools in order to better understand the biological mechanisms involved, discovery of additional adverse health effects of existing and newly developed CNS drugs in the clinical test phase will be lowered.