Manon C. Bouwmeester, Eva J. Streekstra, Yvonne C.M. Staal, J.G.M. van Engelen, Jaco Westra, Mirjam Luijten
New Approach Methodologies (NAMs) play a key role in safety assessment in both Next-Generation Risk Assessment (NGRA) and Safe-and-Sustainable-by-Design (SSbD). Yet the frameworks differ in respective scope, regulatory drivers, and implementation, they share the common goal of providing human-relevant and mechanistic insights into potential adverse health effects. The operationalisation of NAMs within both frameworks present similar, ongoing challenges, such as technical hurdles, but also the need for confidence in NAMs. In a multistakeholder workshop, held in October 2025, researchers, risk assessors, and industry representatives came together to identify opportunities and challenges in integrating NAMs into regulatory (i.e., NGRA) and innovation (i.e., SSbD) contexts. Key topics included the importance of a clear problem formulation and starting chemical safety evaluations with gathering existing information about physicochemical properties and hazards to enable read-across assessments. Both frameworks recommended initial safety assessment based on molecular structures using (quantitative) structure-activity relationship ((Q)SAR) models and properties related to absorption, distribution, metabolism, and excretion (ADME). This guides further NAM-based assessment of bioavailability and hazards. Major challenges include establishing decision frameworks to determine the need for further testing and addressing the iterative nature of safety evaluations, which depend on the specific context of use. Participants advocated for reliable and relevant NAMs, recognising differences in confidence levels required in NGRA versus SSbD. They recommended cross-sector collaboration of users of the two frameworks through case studies and networking. Such collaboration could facilitate mutual learning, harmonisation, and the adoption of NAMs, ultimately supporting safer and more sustainable chemical innovation.