Fractionated charge variants of biosimilars: A review of separation methods, structural and functional analysis


Yuce M., Sert F., Torabfam M., Parlar A., Gurel B., Cakir N., ...More

ANALYTICA CHIMICA ACTA, vol.1152, 2021 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 1152
  • Publication Date: 2021
  • Doi Number: 10.1016/j.aca.2020.12.064
  • Journal Name: ANALYTICA CHIMICA ACTA
  • Journal Indexes: Science Citation Index Expanded, Scopus, Academic Search Premier, Aerospace Database, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), Artic & Antarctic Regions, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, Communication Abstracts, Compendex, EMBASE, Food Science & Technology Abstracts, MEDLINE, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Keywords: Biosimilars, Charge heterogeneity, Chromatography, Electrophoresis, Mass spectrometry, Surface plasmon resonance, CATION-EXCHANGE CHROMATOGRAPHY, THERAPEUTIC MONOCLONAL-ANTIBODIES, NATIVE MASS-SPECTROMETRY, CONTROLLED PH GRADIENTS, ION-EXCHANGE, LIGHT-CHAIN, QUANTITATIVE-ANALYSIS, MULTIPLE SOURCES, RAPID ANALYSIS, SALT GRADIENT

Abstract

The similarity between originator and biosimilar monoclonal antibody candidates are rigorously assessed based on primary, secondary, tertiary, quaternary structures, and biological functions. Minor differences in such parameters may alter target-binding, potency, efficacy, or half-life of the molecule. The charge heterogeneity analysis is a prerequisite for all biotherapeutics. Monoclonal antibodies are prone to enzymatic or non-enzymatic structural modifications during or after the production processes, leading to the formation of fragments or aggregates, various glycoforms, oxidized, deamidated, and other degraded residues, reduced Fab region binding activity or altered FcR binding activity. Therefore, the charge variant profiles of the monoclonal antibodies must be regularly and thoroughly evaluated. Comparative structural and functional analysis of physically separated or fractioned charged variants of monoclonal antibodies has gained significant attention in the last few years. The fraction-based charge variant analysis has proved very useful for the biosimilar candidates comprising of unexpected charge isoforms. In this report, the key methods for the physical separation of monoclonal antibody charge variants, structural and functional analyses by liquid chromatographymass spectrometry, and surface plasmon resonance techniques were reviewed.