A 4R concept for the safety testing of immunobiologicals.

Safety tests in animals are an important part of the licensing procedures for human and veterinary medicines. Pharmacopoeial and other legal regulations require immunobiologicals to be approved for safety on a batch-to-batch basis. A large number of animals is needed to perform these general and specific safety tests. The search for alternatives according to the famous 3R concept proposed by Russel & Burch [1] is also relevant to safety tests. This session of the conference will highlight recent progress in the application of this concept. However, before considering potential alternatives to a test, it is advisable to re-evaluate the necessity of the safety test in question. Many animal-based safety test procedures were introduced because the production of biologicals was difficult and methods to control this production were limited. Nowadays much progress has been achieved due to a better knowledge of the prophylaxis of infectious diseases and the standardisation of methods of production and control. Therefore, some animal tests may no longer be necessary. A good example of this is the deletion of the abnormal toxicity test from the European Pharmacopoeia. Efforts to limit the use of animals in the quality control of immunobiologicals should therefore include a reassessment of the value of the safety test. Consequently, reassessment should be the first R used to evaluate whether an animal test can be removed. The 3R concept of Russel & Burch [1] to replace, reduce and refine animal tests has to be considered if that does not prove to be possible.