Strategies to control therapeutic antibody glycosylation during bioprocessing: synthesis and separation.
Author(s)
Type
Journal Article
Abstract
Glycosylation can be a critical quality attribute (CQA) in biologic manufacturing. In particular, it has implications on the half-life, immunogenicity and pharmacokinetics of therapeutic monoclonal antibodies (mAbs) and must be closely monitored throughout drug development and manufacturing. To address this, advances have been made primarily in upstream processing, including mammalian cell line engineering to yield more predictably glycosylated mAbs, and the addition of media supplements during fermentation to manipulate the metabolic pathways involved in glycosylation. A more robust approach would be a conjoined upstream-downstream processing strategy. This could include implementing novel downstream technologies, such as the use of Fc gamma-based affinity ligands for the separation of mAb glycovariants. This review highlights the importance of controlling therapeutic antibody glycosylation patterns, the challenges faced in terms of glycosylation during mAb biosimilar development, current efforts both upstream and downstream to control glycosylation and their limitations, and the need for research in the downstream space in order to establish holistic and consistent manufacturing processes for the production of antibody therapies. This article is protected by copyright. All rights reserved.
Date Issued
2022-02-19
Date Acceptance
2022-02-10
Citation
Biotechnology and Bioengineering, 2022, 119 (6)
ISSN
0006-3592
Publisher
Wiley
Journal / Book Title
Biotechnology and Bioengineering
Volume
119
Issue
6
Copyright Statement
© 2022 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Biotechnology and Biological Sciences Research Cou
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/35182428
Grant Number
210 22566 (BB/P02789X/1)
Subjects
CQAs
N-glycosylation
antibodies
biosimilars
downstream glycosylation bioprocessing
mAbs
Publication Status
Published online
Coverage Spatial
United States
Date Publish Online
2022-02-19