The expanding field of monoclonal antibody-based pharmaceuticals has triggered increased interest in analytical
characterization of these large proteins and in understanding of their heterogeneity and degradation pathways. As a result,
a large number of enzymatic modifications as well as chemical and physical degradations have been reported in
monoclonal antibodies in recent years. Most heterogeneity is related to changes in the surface charge of the antibody, either
directly, as a change in the number of charged residues, or indirectly as a chemical or physical alteration that changes
surface-charge distribution. This review presents an overview of the sources of charge-related heterogeneity in monoclonal
antibodies and the methods used for their detection. A detailed section is dedicated to deamidation of asparagine
and isomerization of aspartic acid residues, two ubiquitous degradation pathways detected in antibodies and other proteins
as well. Finally, kinetic mode领 of the accumulation of antibody variants is presented as a tool to determine the expected
fraction of molecules that have undergone one or more degradation reactions.
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