title: Safety Pharmacology Evaluation of Biopharmaceuticals.
abstract: Biotechnology-derived pharmaceuticals or biopharmaceuticals (BPs) are molecules such as monoclonal antibodies, soluble/decoy receptors, hormones, enzymes, cytokines, and growth factors that are produced in various biological expression systems and are used to diagnose, treat, or prevent various diseases. Safety pharmacology (SP) assessment of BPs has evolved since the approval of the first BP (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 BP) on the cardiovascular, central nervous, and respiratory systems, referred to as the "core battery," should be assessed prior to first-in-human administration. However, SP assessment of BPs poses unique challenges such as choice of test species and integration of SP parameters into repeat-dose toxicity studies. This chapter reviews the evolution of SP assessment of BPs using the approval packages of marketed BPs and discusses the past, current, and new and upcoming approach and methods that can be used to generate high-quality data for the assessment of SP of BPs.
authors.affiliation: Global Patient Safety, Global Regulatory Affairs & Safety, Amgen Inc, Thousand Oaks, CA, USA.
authors.forename: Hamid R
authors.initials: HR
authors.lastname: Amouzadeh
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Engwall
authors.forename: Hugo M
authors.initials: HM
authors.lastname: Vargas
mesh_terms: D000818:Animals; D001688:Biological Products / Q000009:adverse effects / Q000633:toxicity*; D001709:Biotechnology; D002490:Central Nervous System / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004335:Drug and Narcotic Control; D006801:Humans; D012137:Respiratory System / Q000187:drug effects
chemical_list: D001688:Biological Products