Bridging Innovation and Regulation: Strategic Qualification and Use of New Approach Methodologies in Nonclinical Drug Safety and Efficacy Assessments

The field of nonclinical pharmaceutical development is undergoing a transformative shift as reliance on traditional animal models is increasingly questioned due to translational limitations and ethical considerations. New Approach Methodologies (NAMs), encompassing human relevant in vitro systems, organoids, organs on chip, in silico modeling, and in chemico assays, are emerging as powerful alternatives that align with the 3Rs principles of replacement, reduction, and refinement of animal use. Recent advances in microphysiological systems, computational toxicology, and machine learning have expanded the potential of NAMs to predict human pharmacodynamics, pharmacokinetics, and toxicity more accurately. However, the integration of these tools into routine regulatory frameworks remains limited. Regulatory authorities worldwide are signaling openness to NAM based evidence, but significant questions persist over validation, reproducibility, and context of use specification for decision making, particularly in complex modalities such as biologics, gene therapies, and advanced therapy medicinal products. There is a pressing need for robust, regulator endorsed frameworks that connect scientific innovation with practical implementation.This Research Topic aims to explore strategic approaches for implementing and qualifying New Approach Methodologies in the nonclinical stages of drug development. It seeks to address how NAMs can be systematically selected, combined, and integrated to generate decision relevant data that improves human translatability while maintaining scientific rigor and regulatory acceptance. Key questions include how to define fit for purpose contexts of use, how to harmonize performance expectations between regulators and developers. By synthesizing multidisciplinary insights, this topic intends to establish a roadmap for more routine incorporation of NAMs in regulatory submissions, ensuring they contribute not only to innovation but also to credible, risk informed drug development strategies.To gather further insights into the strategic integration of NAMs across drug development stages, we welcome articles addressing, but not limited to:• Real case applications of in silico and physiologically based pharmacokinetic models for dose selection and exposure prediction• Translational strategies linking NAM endpoints to human biomarkers, exposure levels, and clinical outcomes• Integration of NAMs with PBPK or model informed drug development (MIDD) for dose justification and risk mitigation• Frameworks for regulatory interaction, qualification, and contextualization of NAMs within decision making processes• Strategies to refine or replace animal studies using hybrid developmental designs or targeted reduction approaches• Evolving regulatory guidance and international harmonization efforts toward establishing formal validation and qualification pathwaysWe welcome the following article types: systematic review, methods, policy and practice reviews, technology and code, mini review, perspective, data report, brief research report, general commentary, and opinion. Topic editors: Bjorn Carlsson, Beatriz S Lima, Sabine Maria Poppenborg, Debra Aub Webster Source: https://www.frontiersin.org/research-topics/81486/bridging-innovation-and-regulation-strategic-qualification-and-use-of-new-approach-methodologies-in-nonclinical-drug-safety-and-efficacy-assessments