RESEARCH ARTICLE High-resolution physicochemical characterization of different intravenous immunoglobulin products Nathaniel Washburn1, Robin Meccariello1, Shaohui Hu2, Maurice Hains1, Naveen Bhatnagar1, Hetal Sarvaiya1, Bulbul Kapoor1, John Schaeck1, Ignacio Pino3, Anthony Manning1, Jonathan C. Lansing1, Carlos J. Bosques1* 1 Research, Momenta Pharmaceuticals, Cambridge, Massachusetts, United States of America, 2 Research, CDI Laboratories, Baltimore, Maryland, United States of America, 3 Research, CDI Laboratories, Mayaguez, Puerto Rico * email@example.com Abstract Intravenous immunoglobulin (IVIg) is a complex mixture drug comprising diverse immuno- globulins and non–IgG proteins purified from the plasma of thousands of healthy donors. Approved IVIg products on the market differ regarding source of plasma, isolation process, and formulation. These products are used widely, and often interchangeably, for the treat- ment of immunodeficiency and autoimmune and inflammatory diseases, but their mecha- nisms of action in different indications are not well understood. A primary limitation to understanding the therapeutic relevance of specific components within IVIg has been the limited resolution of analytics historically implemented to characterize its complex mixture. In this study, high-resolution analytics were applied to better understand the composition of IVIg and product variations.Wecharacterized three approved IVIg products: Gammagard®, Privigen®, and Octagam®. Differences in the distribution of molecular weight species, IgG sequence variants, isoforms, glycoforms, and the repertoire of previously reported antibody specificities were identified. Wealso compared the effect of aging on these products to iden- tify changes in size distribution and posttranslational modifications. This type of characteri- zation may provide insights into the specific factors and components of IVIg that may influence its activity and ultimately lead to optimization of IVIg products for use in autoim- mune diseases.
Washburn, N., Meccariello, R., Hu, S., Hains, M., Bhatnagar, N., Sarvaiya, H., … Bosques, C. J. (2017). High-resolution physicochemical characterization of different intravenous immunoglobulin products. PLoS ONE, 12(7). https://doi.org/10.1371/journal.pone.0181251