Analysis Of Intact Glycoprotein Biopharmaceuticals By Capillary Electrophoresis

Many of the biopharmaceuticals currently produced are glycoproteins in which the oligosaccharide chains can impact markedly on bioactivity, antigenicity, pharmacokinetics, solubility, stability, and protease resistance Glycosylation profile may vary based on the host system employed to produce a recombinant glycoprotein Downstream and upstream processes employed to produce the finished product may also significantly impact on the composition of the protein in terms of glycosylation It is therefore mandatory to control glycoproteins by robust methods able to provide sufficient details on minor modifications Capillary electrophoresis (CE) has proved its usefulness not only for the characterization of glycoprotein pharmaceuticals but also as a quality-control (QC) tool allowing accurate quantitation CE has been demonstrated to provide rapid, automated, and quantitative results combined to a high resolving power that meets the requirement for a QC method This chapter focuses on the most recent (as of mid-2009) applications of CE aimed at producing methods to address either QC or characterization issues for intact glycoproteins used as biopharmaceuticals or relevant for clinical or diagnostic purposes For biopharmaceutical applications, the discussion encompasses process monitoring, stability testing, control of the finished product or the purified glycoprotein as well as the influence of process conditions and production steps on the bioproduct structure and glycosylation Also, the implications of the different CE modes (CZE, CIEF, SDS-CGE, and MEKC) are highlighted and discussed