Regulatory momentum for new approach methodologies (NAMs) in medicines development: from vision to implementation

New approach methodologies (NAMs) are increasingly recognised as central to modernising safety assessment in medicines development, offering the potential for improved human relevance, mechanistic insight, and reduced reliance on animal testing. Despite substantial scientific progress and growing regulatory encouragement in their use, the routine integration of NAMs into regulatory decision-making remains inconsistent, even though they are widely used internally across discovery and development. This article brings together several lines of evidence and opinions to explore why uptake continues to lag behind capability, including insights from a cross-sector workshop convened by the Medicines and Healthcare products Regulatory Agency (MHRA), the Association of the British Pharmaceutical Industry (ABPI) and the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). For many applications, the key constraints are no longer scientific, but relate to confidence, clarity of expectations, and implementation, although important scientific challenges remain for complex endpoints such as chronic toxicity. Regulatory frameworks are increasingly supportive, with growing evidence of confidence and alignment on weight-of-evidence approaches incorporating NAMs, yet residual uncertainty and limited practical experience in their application means that questions regarding context-of-use, validation, and regulatory acceptability persist. The next phase requires a shift from technology development to practical implementation, including clearer guidance and increased transparency through the sharing of data and case-studies. Building consensus and confidence across the scientific community will be critical to normalising the use of NAMs and realising their potential in medicines development.