Chemical or enzymatic modifications of therapeutic monoclonal antibodies (mAbs) having high risk towards safety and efficacy are defined as critical quality attributes (CQAs). During therapeutic mAbs process development, a variety of analytical techniques have to be used for the thorough characterization and quantitative monitoring of CQAs. This paper describes the development of a rapid analytical platform to assess and rank charge variants of mAbs. The workflow is first based on a cation exchange chromatography (CEX) comparative analysis of intact IgGs versus F(ab)'2 and Fc sub-domains generated by IdeS digestion. This analytical procedure was validated with FDA and EMA approved mAbs. Then, functional assays and peptide mapping can be performed in a second instance. This approach can be used during the early stage of drug research and development to screen lead molecules and select optimized candidates (best clone, best formulation) which could be "easily" developed (OptimAbs).
Keywords: Cation exchange chromatography; Charge variants; Developability; IdeS; Trastuzumab.
Copyright © 2017. Published by Elsevier B.V.