The EMA (European Medicines Agency) “Reflection paper on the current regulatory testing requirements for human medicinal products and opportunities for implementation of the 3Rs” has been developed as a follow-up to the 2016 “Guideline on the principles of regulatory acceptance of 3Rs (replacement, reduction, refinement) testing approaches”. Its aim is to incorporate newly developed 3Rs (replacement, reduction, refinement) approaches that are now accepted for regulatory decision-making in the risk assessment of human medicinal products.

More specifically, the paper outlines concrete opportunities for reducing or replacing animal use across various domains, including quality, non-clinical, biologics and biosimilars assessment. It also highlights recent revisions to relevant guidelines and provides examples of accepted alternatives, such as in vitro assays and in silico models for pharmacokinetics, toxicity, and immunogenicity studies.

Additionally, the document explores a range of new approach methodologies (NAMs) currently under development, such as the use of virtual control groups and organ-on-chip models, which may further support implementation of the 3Rs.

This reflection paper underscores the EMA’s commitment to scientific innovation, regulatory flexibility, and animal welfare. It also encourages stakeholders, including pharmaceutical developers, researchers, and method developers, to engage with scientific experts from the regulatory network at an early stage to discuss regulatory, technical, and scientific considerations related to novel methodologies development. This dialogue, which can take place for example through the Innovation Task Force, may support the future qualification of 3Rs-compliant approaches.

The document is now open for public consultation until 30 June 2025.