The sweet spot for biologics: recent advances in characterization of biotherapeutic glycoproteins

Expert Rev Proteomics. 2018 Jan;15(1):13-29. doi: 10.1080/14789450.2018.1404907. Epub 2017 Nov 22.

Abstract

Glycosylation is recognized as a Critical Quality Attribute for therapeutic glycoproteins such as monoclonal antibodies, fusion proteins and therapeutic replacement enzymes. Hence, efficient and quantitative glycan analysis techniques have been increasingly important for their discovery, development and quality control. The aim of this review is to highlight relevant and recent advances in analytical technologies for characterization of biotherapeutic glycoproteins. Areas covered: The review gives an overview of the glycosylation trends of biotherapeutics approved in 2016 and 2017 by FDA. It describes current and novel analytical technologies for characterization of therapeutic glycoproteins and is explored in the context of released glycan, glycopeptide or intact glycoprotein analysis. Ultra performance liquid chromatography, mass spectrometry and capillary electrophoresis technologies are explored in this context. Expert commentary: There is a need for the biopharmaceutical industry to incorporate novel state of the art analytical technologies into existing and new therapeutic glycoprotein workflows for safer and more efficient biotherapeutics and for the improvement of future biotherapeutic design. Additionally, at present, there is no 'gold-standard' approach to address all the regulatory requirements and as such this will involve the use of orthogonal glycoanalytical technologies with a view to gain diagnostic information about the therapeutic glycoprotein.

Keywords: Capillary electrophoresis (CE); MS/MS; critical quality attribute (CQA); electrospray ionization-mass spectrometry (ESI-MS); fusion protein; glycopeptide; glycoprotein; immunoglobulin (IgG); monoclonal antibody (mAb); ultra performance liquid chromatography (UPLC).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Products / analysis*
  • Biological Products / chemistry
  • Biological Products / therapeutic use*
  • Glycoproteins / analysis*
  • Glycoproteins / chemistry
  • Glycoproteins / therapeutic use*
  • Glycosylation
  • Humans
  • Polysaccharides / chemistry
  • Therapeutics*

Substances

  • Biological Products
  • Glycoproteins
  • Polysaccharides