3Rs at the European Medicines Agency: Past and future activities

• EMA supports the goal of reducing animal use in regulatory medicines testing. • The 3RsWP advises on 3Rs implementation in regulatory medicines testing in the EU. • EMA is fully committed to global harmonisation on 3Rs approaches. • EMA facilitates uptake of 3Rs methods (e.g. NAMs) via developer interactions. Driven by scientific advancements, the replacement, reduction and refinement of animal use (i.e. the 3Rs principles) in research and testing are gaining momentum. There is increasing interest in the use of innovative testing methods, known as 'New Approach Methodologies' (NAMs), in the regulatory testing of medicines. Such approaches can lead to reduced reliance on animal studies while improving clinical translation and predictivity. Since 2010, the European Medicines Agency (EMA) has advanced the implementation of 3Rs principles in medicines testing through a series of dedicated working groups, culminating in the current 3Rs working party (3RsWP). Key pillars of this work include maintaining up-to-date scientific guidance, engaging with stakeholders and advancing international harmonisation. A key focus in recent years has been fostering regulatory acceptance of NAMs, which has already led to tangible changes. These include the development of stronger scientific guidance, the increased use of existing EMA platforms for early dialogue to promote the regulatory uptake of innovative NAMs, and the establishment of the International Medicines Regulators Working Group on 3Rs (IMRWG3R) to ensure international alignment and harmonisation. This article reviews 15 years of EMA's activities in 3Rs, highlighting the achievements of the 3RsWP and outlining planned future actions and priorities, as it continues to support implementation of the 3Rs in regulatory medicines testing.