Monoclonal antibodies: interspecies scaling with minimal preclinical information.

Interspecies scaling for predicting human pharmacokinetics with information from multiple animal species is an established approach for small-molecule drugs. However, in general, the strategy is not a viable approach for therapeutic monoclonal antibodies, since relevant preclinical information is often limited due to highly specific biological activity and unique disposition mechanisms of these biologic agents. Existing data from a limited database indicates that applying minimal but relevant preclinical information and an appropriate approach; for example, fixed-exponent, provides a pragmatic and reasonably accurate prediction of human pharmacokinetics. This article briefly reviews the factors that affect the disposition of monoclonal antibodies and reiterates the importance of biological similarities between animal species and humans when selecting preclinical information for interspecies scaling. The article outlines the rationalization for utilizing the one-species with fixed-exponent approach, with discussions focused on the assumptions in allometry and monoclonal antibodies disposition mechanisms, and provides specific considerations related to practically applying such an approach.