Application of new approach methodologies for nonclinical safety assessment of drug candidates

Abstract

The development of new approach methodologies (NAMs) and advances with in vitro testing systems have prompted revisions in regulatory guidelines and inspired dedicated in vitro/ex vivo studies for nonclinical safety assessment. This Review by a safety reflection initiative subgroup of the European Federation of Pharmaceutical Industries and Associations (EFPIA)/Preclinical Development Expert Group (PDEG) summarizes the current state and potential application of in vitro studies using human-derived material for safety assessment in drug development. It focuses on case studies from recent projects in which animal models alone proved to be limited or inadequate for safety testing. It further highlights four categories of drug candidates for which alternative in vitro approaches are applicable and discusses progress in using in vitro testing solutions for safety assessment in these categories. Finally, the article highlights new risk assessment strategies, initiatives and consortia promoting the advancement of NAMs. This collective work is meant to encourage the use of NAMs for more human-relevant safety assessment, which should ultimately result in reduced animal testing for drug development. New approach methodologies (NAMs) offer the promise of greater predictivity of potential safety risks of drug candidates, especially for newer types of therapeutics for which animal models alone have limited or no applicability for safety testing. This article identifies four categories of drug candidate for which NAMs are applicable and discusses progress in their use based on case studies from recent projects, as well as initiatives to promote the advancement and use of NAMs for more human-relevant safety assessment.