ABSTRACT
Biopharmaceutical products are generally designed to exhibit high specificity for the intended human target. The toxicities for these compounds are primarily related to the mechanism of action or to immune responses to the biopharmaceutical. As such, the selection of species to derive information on safe use conditions of a given biopharmaceutical product in humans requires the use of appropriate nonclinical species that will exhibit the intended pharmacology after exposure. This approach is consistent with recommendations outlined in ICH S6(R1), the international guideline that describes the preclinical development of biotechnology-derived pharmaceuticals. This chapter explores experimental methods for determining species relevance, overview of nonclinical species for toxicity studies, traditional and alternative models for nonclinical safety assessment, and considerations for specific modalities. The chapters covers the following classes of biopharmaceuticals: antibodies, peptides, oligonucleotides, vaccines, and cell and gene therapies.
