Biologicals can be defined as products that are derived from living organisms or are produced by them. They include vaccines, hormones, monoclonal and polyclonal antibodies, blood products and rDNA products. The production of conventionally produced biologicals requires an extensive batch-related quality control, to ensure that these products are both safe and potent. As several of the control tests rely on animal models, it is inevitable that the large numbers of animals are used. Many initiatives have been undertaken in the last few decades to reduce and refine the use of animals in this area. ECVAM has been involved in many activities to support the development, validation and implementation of these Three Rs methods. The role that ECVAM has played in a number of validation studies is summarised. It is concluded that ECVAM should continue to support the activities that have been shown to be successful, preferably in collaboration with the regulatory bodies.