Clinical Pathology in Nonclinical Toxicity Testing

Abstract Hematologic analysis, hemostasis evaluation, clinical chemistry testing, and urinalysis form a minimal data base of clinical pathology testing used to evaluate therapeutic agents (new chemical entities, test articles, and biologics), pesticides, and industrial chemicals in nonclinical safety assessment studies. Results of clinical pathology testing are communicated to regulatory authorities and generally form the basis for development of a monitoring strategy for molecules in development. We describe the selection of appropriate tests for hematology, hemostasis, clinical chemistry, and urinalysis in toxicity testing. Characteristics of a high-quality clinical pathology laboratory and body fluid sample requirements are described. Factors that affect the optimal design of the clinical pathology component of protocols to optimize the opportunity to achieve study objectives are discussed. Additional tests may be included in study protocols to help characterize the mechanism of test article action, to assist in prioritization of candidate molecules, or to address requests by regulatory authorities; these ancillary tests include acute phase proteins, hormones, and exploratory and established biomarkers of renal, hepatic, cardiac, and vascular injury. The importance of designing the clinical pathology component of study protocols and integrating findings with other study results in the evaluation of overall safety or risk assessment is highlighted.