Transitional initiatives for advancing the phasing out of the use of animals for drug and chemical safety testing: The IHI VICT3R project for reducing the use of animals by implementing virtual control groups.

Despite rapid advances in human-relevant assay technologies and other innovative in vitro and in silico approaches, the safety assessment of chemicals and pharmaceutical drugs continues to heavily rely on animal testing, in part due to slow regulatory adaptation and a lack of transitional strategies that clear the way for the phasing out of animal testing while demonstrating the preservation of current safety standards. To overcome this hurdle, several international efforts are currently focused on systematically integrating new approach methodologies (NAMs) into regulatory frameworks with the goal of phasing out animal testing in the safety assessments. The present paper highlights the need for pragmatic transitional initiatives that reduce animal use while preserving scientific rigor and regulatory confidence by focusing on the IHI VICT3R project, a collaborative effort aimed at reducing animal use in safety assessments of drugs and chemicals by replacing concurrent control groups with virtual control groups (VCGs). The VICT3R project focuses on refining and implementing the VCG methodology, particularly in the standardization, curation and adequate matching of historical control data (HCD), as well as regulatory qualification. Beyond regulatory applications, the VCG concept constitutes a scalable paradigm for reducing the experimental animal use in academic and industrial research. By demonstrating how data-driven approaches can reduce animal use without compromising scientific quality, VICT3R offers an expandable model for advancing the global transition toward non-animal testing frameworks. Moreover, implementing the VCG methodology in a regulatory context could pave the way to the successful incorporation of other NAMs. The paper stresses the required paradigm shift, which involves adequate qualification procedures, cross-sector collaboration, and a cultural shift away from animal testing.