Developmental neurotoxicity as a case example for a six-step framework for the sustainable regulatory implementation of NAMs
Jonathan Blum, Kristina Bartmann, Joyce de Paula Souza, Ellen Fritsche
Abstract
New Approach Methodologies (NAMs) are advancing toxicology by offering reliable, human-relevant alternatives to traditional animal methods. This review outlines a six-step framework guiding NAMs from development to regulatory approval, using the Developmental Neurotoxicity (DNT) in vitro battery (IVB) as an example. The framework begins with the development of robust test systems with human-relevant models (step 1). Next, a NAM-based roadmap aligns testing strategies with regulatory needs and encourages early stakeholder engagement (step 2). Test method readiness is assessed for biological relevance, reproducibility, and reliability (step 3). Scientific validation includes technical characterization, independent expert review, and transparent public data sharing (step 4). OECD recognition ensures a rigorous evaluation process before NAMs are included in official guidelines (step 5). Lastly, public availability through Contract Research Organizations (CROs) guarantees compliance with Good Laboratory Practice (GLP) and facilitates regulatory adoption (step 6). This DNT IVB lifecycle exemplifies the implementation of NAMs, continuously evolving with scientific progress. It supports initiatives like the European Roadmap towards phasing out animal testing and the Safe and Sustainable by Design (SSbD) framework under the European Green Deal. By providing a structured pathway, this lifecycle approach fosters NAM-based, human-centric risk assessments for a more sustainable future in chemical safety testing.