Chapter 15 - Best Practice in Toxicologic Pathology

Abstract

Toxicological pathology is a critical component of the safety assessment of new drug candidates, especially in drug development driven by a translational research approach trying to improve and accelerate efficacy and safety evaluation. The identification and interpretation of drug-induced histopathological changes require skilled pathologists and technical staff who generate and interpret high-quality data. The pathologists integrate clinical pathology, organ weights, cytokines, or immunophenotyping data and should have access to the other phase reports such as toxicokinetic. The histopathological changes are recorded in a consistent manner in a laboratory investigation management system using internationally agreed standardized nomenclature and stating the severity and distribution of the lesion. It is the role of the pathologist to distinguish between the lesions that are either spontaneous and of unknown cause or that represent normal morphological variations in a tissue at different functional phases, and the lesions that are induced by the test article under assessment. The pathologist also determines the adversity of a lesion for the study on a weight-of-evidence basis. The standardization of necropsy, tissue collection and processing, and the use of standardized nomenclature in histopathology, together with a robust pathology peer review, guarantee the quality, consistency, and integrity of data and their interpretation. The best practices strictly adhere to guidelines and standard operating procedures (SOPs). The purpose of this chapter is to describe best practices in the processes and procedures in toxicological pathology that are necessary for the generation of valid study results and interpretation. The role and needed training of the toxicologic pathologist will be presented, and the specificity of various therapeutic modalities such as small molecules, biologics, and cell and gene therapy products will be discussed from a pathology viewpoint.