From Scientific Promise to Regulatory Practice: Stakeholder Perspectives on New Approach Methodologies

Abstract

New Approach Methodologies (NAMs) are increasingly developed as human-relevant alternatives or complements to animal models in drug development and safety assessment. Despite rapid scientific progress, their regulatory uptake remains limited, highlighting the need to better understand how stakeholders perceive their value and readiness. This study examines stakeholder perceptions of in vitro NAMs in regulatory drug testing, with a focus on human relevance, validation requirements, regulatory acceptance and ethical governance.

A narrative literature review was conducted using PubMed, focusing on interviews, surveys, workshops, perspective papers and meeting reports addressing stakeholder views on NAMs in a regulatory context. Data were extracted on stakeholder groups, application domains, stakeholder attitudes, and reported barriers and opportunities.

Across academia, industry, regulatory agencies, and donor/public communities, NAMs are recognised as scientifically promising tools with potential to improve human relevance compared to animal models. However, perceptions of regulatory readiness differ between stakeholder groups. Academia emphasises mechanistic insight, industry prioritises predictive validity, reproducibility, and scalability, while regulators stress the need for clearly defined contexts of use and transparent validation and qualification pathways. Commonly reported barriers include technical heterogeneity, limited standardisation, insufficient validation and reference data, unclear regulatory expectations and governance challenges related to donor consent, data use, and commercialisation.

Although ongoing initiatives by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) provide a foundation for addressing these issues, NAMs are currently considered insufficiently mature to replace animal models in regulatory drug testing. Progress is most realistically achieved through clearly defined contexts of use and further validation, supported by collaboration among stakeholders.