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.
Authors
- Radhakrishna Sura (ORCID: https://orcid.org/0000-0001-6337-5588)
- Kerstin Hahn (ORCID: https://orcid.org/0000-0003-3602-4234)
- Randolph S. Ashton (ORCID: https://orcid.org/0000-0002-6842-7022)
- Dirk Schaudien (ORCID: https://orcid.org/0000-0001-7398-7262)
- Danilo A. Tagle (ORCID: https://orcid.org/0000-0003-0071-4612)
- Deidre A. Dalmas (ORCID: https://orcid.org/0000-0003-3641-139X)
- Julia Kühnlenz
- Martina Stirn
- Passley Hargrove-Grimes (ORCID: https://orcid.org/0000-0002-7644-0462)
- Brian R. Berridge (ORCID: https://orcid.org/0000-0003-1988-2819)
- J. D. Baily
- Charles Havnar (ORCID: https://orcid.org/0000-0003-1505-0505)
- Lindsay Tomlinson (ORCID: https://orcid.org/0009-0000-9527-7763)
- Steven T. Laing (ORCID: https://orcid.org/0000-0002-6079-3095)
- Eliah R. Shamir (ORCID: https://orcid.org/0000-0002-2417-3294)
- Nadine Stokar‐Regenscheit (ORCID: https://orcid.org/0000-0003-4089-2026)
- Tanja S. Zabka (ORCID: https://orcid.org/0009-0004-1225-6844)
- Frédéric Schorsch (ORCID: https://orcid.org/0000-0001-7825-3823)
- Camila Dores (ORCID: https://orcid.org/0009-0008-2046-6082)
Institutions
- Roche (Switzerland) (CH)
- University of Wisconsin–Madison (US)
- Alnylam Pharmaceuticals (United States) (US)
- Charles River Laboratories (United Kingdom) (GB)
- Fraunhofer Institute for Toxicology and Experimental Medicine (DE)
- Boehringer Ingelheim (Egypt) (EG)
- Gilead Sciences (United States) (US)
- National Center for Advancing Translational Sciences (US)
- Boehringer Ingelheim (United States) (US)
- Bayer (France) (FR)
Publication Details
- Journal
- Toxicologic Pathology
- Published
- 2026-08-28
- DOI
- https://doi.org/10.1177/01926233261455350
- Primary Topic
- Immunotoxicology and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00