Non-clinical safety assessments using human cells for pediatric drug development

Abstract

Pediatric drug development is an urgent need to provide appropriate therapies for pediatric patients. Because children are undergoing continuous growth and development of their body and organs, pharmacological responses to the same drugs may differ from those observed in adults. Clinical trials in children are essential to evaluate efficacy and safety in pediatric populations; however, pediatric drug development faces multiple challenges, including the limited number of eligible patients. To improve the safety and efficiency of clinical trials, it is important to confirm the safety and efficacy of developing drugs at non-clinical stages. For improving the predictability of human drug responses and promoting alternatives to animal experiments, new approach and methodologies (NAMs), such as human cell-based models and organoids, have been developed and applied in drug development. NAMs which can recapitulate pediatric-specific characteristics have the potential to contribute to appropriate non-clinical assessments of safety and efficacy in pediatrics. Here, we introduce our recent approaches using human cell models for the development of pediatric heart failure therapeutics and for in vitro assessment of drug-induced liver injury risk in pediatrics. In addition, we discuss internal and global efforts to improve non-clinical assessment strategies for pediatric drug development.