State of the industry: integration of 3Rs principles and new approach methodologies in non-clinical product development through fit-for-purpose.

Regulators, such as the FDA and EMA, are increasingly signaling expectations for broader and earlier adoption of New Approach Methodologies (NAMs) to reduce, refine, and, where justified, replace animal studies (3Rs principle)-particularly where NAMs can deliver improved human relevance, clearer mechanistic insight, or more efficient regulatory decision-making. This creates both an opportunity and a responsibility for drug developers: NAMs should no longer be viewed solely as exploratory tools, but as strategic components of an integrated pivotal non-clinical data package. This is already enshrined in various regulatory guidelines, roadmaps and position papers, but there is no single "approved list" of NAMs for pharmaceutical safety and efficacy assessment that applies across all products and agencies. Regulators explicitly support NAM adoption when scientifically sound, qualified for a defined context of use (COU), and integrated under a weight-of-evidence (WoE) approach. To support drug developers in responding to these expectations, a stepwise approach to expand the use of scientifically validated NAMs, such as