Designing an Artificial Golgi Reactor to achieve targeted glycosylation of monoclonal antibodies
File(s)Klymenko_et_al-2016-AIChE_Journal.pdf (1.01 MB) AIChEJ resubmission.pdf (2.25 MB)
Published version
Accepted version
Author(s)
Klymenko, O
Royle, K
Polizzi, KM
Shah, N
Kontoravdi, C
Type
Journal Article
Abstract
The therapeutic efficacy of monoclonal antibodies (mAbs) is dependent upon their glycosylation
patterns. As the largest group of currently approved biopharmaceuticals, the microheterogeneity in
mAb oligosaccharide profiles deriving from mammalian cell production is a challenge to the
biopharmaceutical industry. Disengaging the glycosylation process from the cell may offer significant
enhancement of product quality and allow better control and reproducibility in line with the Quality by
Design paradigm. Three potential designs of an Artificial Golgi reactor implementing targeted sequential
glycosylation of mAbs are proposed including a (i) microcapillary film reactor, (ii) packed bed reactor
with non-porous pellets, and (iii) packed bed reactor with porous pellets. Detailed mathematical models
are developed to predict their performance for a range of design and operational parameters. While all
three reactor designs can achieve desired conversion levels, the choice of a particular one depends on
the required throughput and the associated cost of enzymes and co-substrates.
patterns. As the largest group of currently approved biopharmaceuticals, the microheterogeneity in
mAb oligosaccharide profiles deriving from mammalian cell production is a challenge to the
biopharmaceutical industry. Disengaging the glycosylation process from the cell may offer significant
enhancement of product quality and allow better control and reproducibility in line with the Quality by
Design paradigm. Three potential designs of an Artificial Golgi reactor implementing targeted sequential
glycosylation of mAbs are proposed including a (i) microcapillary film reactor, (ii) packed bed reactor
with non-porous pellets, and (iii) packed bed reactor with porous pellets. Detailed mathematical models
are developed to predict their performance for a range of design and operational parameters. While all
three reactor designs can achieve desired conversion levels, the choice of a particular one depends on
the required throughput and the associated cost of enzymes and co-substrates.
Date Issued
2016-07-15
Date Acceptance
2016-06-21
Citation
AICHE Journal, 2016, 62 (9), pp.2959-2973
ISSN
0001-1541
Publisher
Wiley
Start Page
2959
End Page
2973
Journal / Book Title
AICHE Journal
Volume
62
Issue
9
Copyright Statement
Available via Open Access at http://onlinelibrary.wiley.com/doi/10.1002/aic.15388/abstract
Sponsor
Engineering & Physical Science Research Council (E
Engineering & Physical Science Research Council (EPSRC)
Grant Number
09066
EP/K038648/1
Subjects
Chemical Engineering
0904 Chemical Engineering
0914 Resources Engineering And Extractive Metallurgy
Publication Status
Published