Preclinical development of therapeutic biologics

Background: To support the increasing number of biologics in drug discovery, preclinical development programs (PDPs) adopted for biologics are needed. Objective: Differences in the physiochemical properties of biologics compared with small molecules require the adaptation of the standard PDP, incorporating tools specific for the characterization of biologics. Methods: Preclinical development addressed in this review comprises preclinical and clinical bioanalytics, preclinical pharmacokinetics and nonclinical drug safety. Despite varying expectations for specific preclinical development of biologics across the industry, standard development plans are emerging for biologics, distinct to those well established for small molecules, driven by lessons learned from past experience and new regulatory guidance. Results/conclusions: The PDP for biologics should be adapted to account for: target differences, lack of species crossreactivity and/or limited applicability of long-term studies as well as immunogenicity assessment. Special study designs may partially overcome these hurdles and should be scientifically justified.