Safety Pharmacology Evaluation of Biopharmaceuticals

Biotechnology-derived pharmaceuticals or biopharmaceuticals are molecules such as monoclonal antibodies, bispecific antibodies, soluble/decoy receptors, hormones, enzymes, cytokines, and growth factors that are used to diagnose, treat, or prevent various diseases. Safety pharmacology assessment of biopharmaceuticals has evolved since the approval of the first example (recombinant human insulin) in 1982. This evolution is ongoing and is informed by various International Harmonization Guidelines. Based on these guidelines, the potential undesirable effect of every drug candidate (small molecule or large molecule) on the cardiovascular, central nervous, and respiratory systems, referred to as the “Core Battery,” should be assessed prior to first-in-human administration. However, assessment of biopharmaceuticals poses unique challenges such as choice of test species and integration of relevant safety pharmacology parameters into repeat-dose toxicity studies. This chapter reviews the evolution of assessment of biopharmaceuticals using examples from approval packages of marketed agents and discusses the past, current, and new approaches and methods that can be used to generate high-quality data for the safety pharmacology assessment of biopharmaceuticals.