Quality Issues Arising From Post-Translational Modification Of Recombinant Antibodies

This chapter explores the post translational modifications (PTMs) that can occur in recombinant monoclonal antibodies. The topic of glycosylation is covered in another chapter in this volume. These modifications can occur at each stage of bioprocessing i.e. cell expansion, fermentation, protein purification, formulation and long-term storage. The chapter focusses on the following PTMs: protein aggregation and misfolding, dimerization, oxidation (principally of methionine residues), and deamidation (principally of asparagine residues). It explores the mechanisms and possible causes of these PTMs, and also the assays used to track these changes. It is the responsibility of each manufacturer to define the limits of variation that exist for individual biopharmaceuticals through comprehensive analytics and submit these to the regulatory authorities. These limits, along with parameters defined during Quality by Design programs (QbD) using Process Analytical Technologies (PAT) are used to optimize the bioprocessing steps to minimize the presence of aberrant species.