Transgenic animals pharmacological models

In recent years studies have been developed in spontaneous disease models, gene knock out models and transgenic animals. These models provide information on the pharmacological action, pharmaco-kinetics and tolerability of a biotech products. 

Animal Species/Model Selection. Safety evaluation should include the use of relevant species, in which the test article is pharmacologically active due, for example, to the expression of the appropriate receptor molecule. These can be screened with in vitro rector binding assays. Safety evaluation should normally include two appropriate species, if possible and/or feasible. The potential utility of gene knockout and/or transgenic animals in safety assessment is discussed. 

The use of nonrelevant animal species is discouraged as the results of such studies may be misleading (per ICH S6). Therefore the next option, when available, is to substitute a relevant transgenic animal model for a pharmacologically relevant species. Transgenic animal models for human EpCAM have been developed, but they either have a different tissue expression pattern from that seen in humans [41,43] or the model has not been validated [40], making them unsuitable for the evaluation of the safety of anti-EpCAM immunotherapeutics. 

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