Use of animal models of human disease for nonclinical safety assessment of novel pharmaceuticals.

Animal models of human disease are commonly utilized to gain insight into the potential efficacy and mode of action of novel pharmaceuticals. However, conventional (healthy) rodent and nonrodent models are generally utilized in nonclinical safety testing. Animal models of human disease may be helpful in understanding safety risks of compounds in nonclinical or clinical development, with their greatest value being in targeted or hypothesis-driven studies to help understand the mechanism of a particular toxicity. Limitations of animal models of disease in nonclinical safety testing include a lack of historical control, heterogeneity in disease expression, a limited life span, and confounding effects of the disease. In most instances, animal models of human disease should not be utilized to supplant testing in conventional animal models. While of potential benefit, testing in an animal model of human disease should only be taken after adequate consideration of relevance along with benefits and limitations of the proposed model.