Safety Pharmacology in the Era of Precision Medicine

Abstract

Safety Pharmacology (SP) plays a critical role in assessing the potential adverse effects of drugs on vital organ systems during the early stages of drug discovery and development. The field of SP has evolved to incorporate various methodologies and testing strategies. In the era of Precision Medicine (PM), SP contributes to the development of PM drugs by ensuring their safety in specific subpopulations. However, it is noted that the SP considerations for PM therapies differ from those for conventional drug candidates. For cell therapies, SP studies must consider the unique characteristics of these products. SP in gene therapies focuses on the safety of genetic material transfer using viral vectors, while CAR-T cell therapies pose the challenges of human cellular products and genome editing vectors. PM also plays a role in SP by identifying robust biomarkers that aid in safety assessment, monitoring, and predicting toxicity. The PM-inspired biomarkers enhance our understanding of how a drug works, help select the right patients for clinical trials, and guide regulatory decisions. Moreover, PM enables the invention of new modalities for SP experiments, such as spheroids, organoids, and organ-on-a-chip models, which provide biologically relevant and stable in vitro systems. Personalized organ-on-a-chip models hold promise for individually assessing drug efficacy and safety, supporting personalized disease prevention and treatment strategies. Experts in both SP and PMrecognize the importance of updating SP guidelines to incorporate the advancements of PM. Multidisciplinary efforts are expected to lead to remarkable advances in drug development, ultimately benefiting healthcare

Keywords: Biomarkers, Cellular-And-Genetic Therapies, Organ-On-Chip, Precision Medicine, Safety Pharmacology