The European Medicines Agency (EMA) has taken a significant step towards more ethical and innovative medicines development. Its Committee for Medicinal Products for Human Use (CHMP) has issued a draft qualification opinion on a novel methodology in non-clinical research that could reduce the number of animals used in toxicity studies.
At the core of this development is the introduction of virtual control groups, designed to replace traditional concurrent animal control groups, particularly in dose-range finding studies in rats. These virtual groups are constructed using existing control data and statistical methods, supported by expert judgement.
By qualifying this new approach methodology (NAM), the CHMP acknowledges that, within a clearly defined context of use, evidence generated using virtual control groups may be accepted as scientifically valid in future marketing authorisation applications.
While the reduction in animal use is expected to be gradual, this represents the first qualification opinion for a NAM applied to toxicity assessment, effectively establishing a blueprint for broader regulatory adoption.
Notably, the methodology could also be extended to other toxicological studies where control groups are routinely required. If scaled, the replacement of physical control groups with virtual counterparts could lead to a substantial decrease in the total number of animals used in medicines development.
Although this qualification opinion is not specific to rare diseases, it is relevant for a field where early-stage research can be constrained by small development programmes, limited disease-relevant models and the need to use available evidence as efficiently as possible. For rare disease therapy development, regulatory acceptance of well-validated, data-driven approaches could help streamline early non-clinical decision-making, provided that patient safety remains central and that historical control data are carefully selected, comparable and transparently interpreted.
This initiative is part of EMA’s broader commitment to the 3Rs principles — Replace, Reduce and Refine — in animal research. It also aligns with ongoing efforts by the International Coalition of Medicines Regulatory Authorities (ICMRA) to promote alternative testing strategies that reduce or eliminate animal use in regulatory science, while maintaining rigorous standards for safety and scientific validity.
The draft qualification opinion is currently open for public consultation from 31 March to 12 May 2026. EMA invites input from the scientific community and stakeholders, with submissions to be sent to ScientificAdvice@ema.europa.eu using the designated template.