Constrained global sensitivity analysis for bioprocess design space identification
File(s)CACE_accepted paper.pdf (1.63 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
The manufacture of protein-based therapeutics presents unique challenges due to limited control over the biotic phase. This typically gives rise to a wide range of protein structures of varying safety and in vivo efficacy. Herein we propose a computational methodology, enabled by the application of constrained Global Sensitivity Analysis, for efficiently exploring the operating
range of process inputs in silico and identifying a design space that meets output constraints. The methodology was applied to an antibody-producing Chinese hamster ovary (CHO) cell culture system: we explored >8000 feeding strategies to identify a subset of manufacturing conditions that meet constraints on antibody titre and glycan distribution as an attribute of product quality. Our computational findings were then verified experimentally, confirming the applicability of this approach to a challenging production system. We envisage that this methodology can significantly expedite bioprocess development and increase operational flexibility.
range of process inputs in silico and identifying a design space that meets output constraints. The methodology was applied to an antibody-producing Chinese hamster ovary (CHO) cell culture system: we explored >8000 feeding strategies to identify a subset of manufacturing conditions that meet constraints on antibody titre and glycan distribution as an attribute of product quality. Our computational findings were then verified experimentally, confirming the applicability of this approach to a challenging production system. We envisage that this methodology can significantly expedite bioprocess development and increase operational flexibility.
Date Issued
2019-06-09
Date Acceptance
2019-01-21
Citation
Computers and Chemical Engineering, 2019, 125, pp.558-568
ISSN
1873-4375
Publisher
Elsevier
Start Page
558
End Page
568
Journal / Book Title
Computers and Chemical Engineering
Volume
125
Copyright Statement
© 2019 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Biotechnology and Biological Sciences Research Cou
Grant Number
EP/K038648/1
PoC Nov15 Kontoravdi
Subjects
0904 Chemical Engineering
0913 Mechanical Engineering
Chemical Engineering
Publication Status
Published
Date Publish Online
2019-03-14