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Post-translational structural modifications of immunoglobulin G and their effect on biological activity

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Abstract

The size, heterogeneity, and biological production process of protein therapeutics like monoclonal antibodies create unique challenges for their analysis and regulation compared with small molecules. Complete structural characterization of a molecule 1000-fold heavier than aspirin is no small feat. Biological post-translational modifications such as glycosylation further complicate their characterization and regulation. Even approved protein therapeutics are known to contain multiple structural variants in differing amounts. Structural modification occurs during production and storage as well as within patients after administration. Thus, the goals of manufacturers and regulators are to control and characterize this heterogeneity, not take on the impossible task of eliminating it. The aim of this review is to describe the structural heterogeneities known to occur with immunoglobulin G (IgG), note current detection and analytical strategies, establish their causes, and define their potential effects on the ultimate safety, purity, and potency of antibody therapeutics when known.

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  1. Center for Drug Evaluation and Research, Office of Testing and Research, Division of Pharmaceutical Analysis, United States Food and Drug Administration, Saint Louis, MO, 63110, USA

    Laura K. Hmiel & Michael T. Boyne II

  2. Center for Drug Evaluation and Research, Office of Biotechnology Products, Division of Monoclonal Antibodies, United States Food and Drug Administration, Silver Spring, MD, 20993, USA

    Kurt A. Brorson

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Hmiel, L.K., Brorson, K.A. & Boyne, M.T. Post-translational structural modifications of immunoglobulin G and their effect on biological activity. Anal Bioanal Chem 407, 79–94 (2015). https://doi.org/10.1007/s00216-014-8108-x

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