A Multidimensional Analytical Comparison of Remicade and the Biosimilar Remsima.
Karthik PisupatiYuwei TianSolomon OkbazghiAlexander BenetRose AckermannMichael FordSergei SavelievChristopher M HosfieldMarjeta UrhEric CarlsonChristopher BeckerThomas J TolbertSteven P SchwendemanBrandon T RuotoloAnna A SchwendemanPublished in: Analytical chemistry (2017)
In 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 more than 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 the level of FcγIIIa receptor 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 because of 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.
Keyphrases
- monoclonal antibody
- mass spectrometry
- liquid chromatography
- drug administration
- high resolution
- binding protein
- end stage renal disease
- amino acid
- newly diagnosed
- ejection fraction
- systematic review
- chronic kidney disease
- hydrogen peroxide
- high performance liquid chromatography
- nitric oxide
- prognostic factors
- risk assessment
- current status
- high density
- social media
- small molecule
- quantum dots
- climate change
- electronic health record
- artificial intelligence