Implementation of three Rs alternatives in regulatory testing: possibilities and obstacles--the view of the validator

After the establishment of the European Centre for the Validation of Alternative Methods (ECVAM) in 1993, the Scientific Advisory Committee (ESAC) decided at its first meeting that the implementation of the Three Rs in the production and quality control of biologicals should be one of ECVAMs priorities. In collaboration with experts, ECVAM has established guidelines on the pre-validation and validation of alternative toxicological methods, which are as applicable to alternative methods in the quality control of biologicals as they are to the testing of industrial chemicals. This paper explains the technical information which should be submitted to ECVAM to assess the readiness of a method for pre-validation, which is defined as a small-scale interlaboratory study to confirm that an optimised and transferable protocol is available. Where appropriate, a formal validation study is then conducted, to evaluate the scientific relevance and reliability of the test method.