Posttranslational biopharmaceutical

Capillary electrophoresis has widespread applications in the field of biopharmaceuticals, particularly for product characterization. It is a technique particularly well suited for assessing product heterogeneity arising from posttranslational modifications, degradation, or genetic variation. There are several CE modes, based on different separation mechanisms, which, alone or in combination, can be used (Table 1). The choice of the most appropriate CE separation mode, or combination thereof, will depend on the nature of the product under study and the type of information required. In the following sections, a brief overview of the use of CE for the characterization of biopharmaceuticals with respect to product identity and purity will be presented. 

Most smaU-molecule drugs are produced by direct cheanical synthesis. Multiple steps can be involved as various intermediate molecules are created on the pathway to eventually synthesizing the desired molecnle. In contrast, larger-scale manufacture of biopharmaceuticals involves the employment of host cells to produce proteins that are safe and effective (Ho and Gibaldi 2003). The choice to use prokaryote host cells (prokaryotes are microorganisms with no distinct membrane-bound nucleus), lower eukaryote cells, or higher eukaryote (mammalian) cells, which becomes progressively more expensive in the order just listed, is predicated on what kind of host cell is needed to carry out necessary posttranslational modifications. 

Hundreds of modifications to the protein backbone have been reported and reviewed." ° For many biopharmaceutical proteins, however, only a handful of modifications are usually detected. These include both posttranslational modifications that are results of intracellular enzymatic processes, and covalent modifications that occur during or after the manufacturing process, either induced by process conditions or resulting from degradation (discussed in Section II.A.4). 

Brown, M. A. and Stenberg, L. M. Biopharmaceuticals Post-translational modification carboxyl-ation and hydroxylation. In Posttranslational Modifcation of Protein Biopharmaceuticals, (G. Walsh, ed.), Wiley-VCH, Weinheim, pp. 210-252, 2009. 

---