Toxicologic Pathology Forum: ESTP/STP Working Group Opinion on the Evolving Landscape of New Approach Methodologies in Drug and Chemical Safety Development.

In April 2025, the US Food and Drug Administration (FDA) introduced a bold roadmap to phase out animal testing in drug development by promoting the integration of New Approach Methodologies (NAMs), beginning with monoclonal antibodies (mAbs). Similar roadmaps have also been created by European health authorities and chemical safety agencies around the globe. This opinion paper from the European Society of Toxicologic Pathology and US Society of Toxicologic Pathology complex in vitro model and pathology working groups provides a balanced and expert perspective on the promise and limitations of these initiatives. NAMs, including in vitro, in silico, and refined in vivo models, offer exciting opportunities to improve human relevance, efficiency, and ethical standards in nonclinical safety assessment. While these approaches are already making meaningful contributions, current scientific and technical limitations prevent them from fully replacing animal studies in all contexts. At this time, NAMs should be viewed as powerful complementary tools whose appropriate integration depends on the context of use, validation, and continued collaboration across disciplines. Pathologists and investigative molecular pathology leaders are uniquely positioned to support this transition by bridging traditional methods with emerging technologies to enhance the safety and effectiveness of future therapeutics.