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dc.contributor.authorPisupati, Karthik
dc.contributor.authorTian, Yuwei
dc.contributor.authorOkbazghi, Solomon Zeray
dc.contributor.authorBenet, Alexander
dc.contributor.authorAckermann, Rose
dc.contributor.authorFord, Michael
dc.contributor.authorSaveliev, Sergei
dc.contributor.authorHosfield, Christopher M.
dc.contributor.authorUrh, Marjeta
dc.contributor.authorCarlson, Eric
dc.contributor.authorBecker, Christopher
dc.contributor.authorTolbert, Thomas J.
dc.contributor.authorSchwendeman, Steven P.
dc.contributor.authorRoutolo, Brandon T.
dc.contributor.authorSchwendeman, Anna
dc.date.accessioned2017-10-09T17:30:45Z
dc.date.available2017-10-09T17:30:45Z
dc.date.issued2017-04
dc.identifier.citationPisupati, K., Tian, Y., Okbazghi, S., Benet, A., Ackermann, R., Ford, M., … Schwendeman, A. (2017). A Multidimensional Analytical Comparison of Remicade and the Biosimilar Remsima. Analytical Chemistry, 89(9), 4838–4846. http://doi.org/10.1021/acs.analchem.6b04436en_US
dc.identifier.urihttp://hdl.handle.net/1808/25101
dc.description.abstractIn April 2016, the Food and Drug Administration approved the first biosimilar monoclonal antibody (mAb) – Inflectra/Remsima (Celltrion) based off the original product Remicade (infliximab, Janssen). Biosimilars promise significant cost savings for patients, but the unavoidable differences between innovator and copycat biologics raise questions regarding product interchangeability. In this study, Remicade and Remsima were examined by native mass spectrometry, ion mobility and quantitative peptide mapping. The levels of oxidation, deamidation and mutation of individual amino acids were remarkably similar. We found different levels of C-terminal truncation, soluble protein aggregates and glycation that all likely have a limited clinical impact. Importantly, we identified over 25 glycoforms for each product and observed glycoform population differences, with afucosylated glycans accounting for 19.7% of Remicade and 13,2% of Remsima glycoforms, which translated into a 2-fold reduction in FcγRIIIa binding for Remsima. While this difference was acknowledged in Remsima regulatory filings, our glycoform analysis and receptor binding results appear to be somewhat different from the published values, likely due to methodological differences between laboratories and improved glycoform identification by our laboratory using a peptide map-based method. Our mass spectrometry based analysis provides rapid and robust analytical information vital for biosimilar development. We have demonstrated the utility of our multiple attribute monitoring workflow using the model mAbs Remicade and Remsima, and have provided a template for analysis of future mAb biosimilars.en_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsCopyright © 2017 American Chemical Societyen_US
dc.subjectBiosimilarsen_US
dc.subjectMonoclonal antibodiesen_US
dc.subjectIon-mobilityen_US
dc.subjectGlycosylationen_US
dc.subjectMass spectrometryen_US
dc.titleA Multidimensional Analytical Comparison of Remicade and the Biosimilar Remsimaen_US
dc.typeArticleen_US
kusw.kuauthorOkbazghi, Solomon
kusw.kuauthorTolbert, Thomas J.
kusw.kudepartmentPharmaceutical Chemistryen_US
dc.identifier.doi10.1021/acs.analchem.6b04436en_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC5599217en_US
dc.rights.accessrightsopenAccess


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