NAMs: Beta testing needed

Abstract

A variety of new approach methodologies (NAMs) have already been developed for acute systemic and short-term toxicity, including in vitro, in silico, and omics methods. To advance their regulatory implementation, we suggest that beta testing of these methods in regulatory settings is urgently needed. There are several limitations to the use of NAMs for acute systemic and short-term toxicity, such as the lack of definitions for applicability domains, skewed reference data for validation, and the absence of representation of kinetic processes and multi-organ complexity. These limitations may lead to risks associated with the ordinary regulatory implementation, such as the application of methods to substances outside of their intended applicability domain or reduced predictivity due to a lack of mechanistic information or consideration of kinetics. We argue that this could be avoided by beta testing. Further benefits of beta testing would be the filling of in vivo data gaps and potentially improved validation with regard to human relevance of methods. In order to enhance the improvement, familiarisation, and acceptance of NAMs in the near future, it is essential for such concept of beta testing to rely on feedback loops between method testers and developers.