Biotechnology Progress - 2021 - Shariatzadeh - Application of a simple unstructured kinetic and cost of goods models to.pdf (2.96 MB)
Download fileApplication of a simple unstructured kinetic and cost of goods models to support T-cell therapy manufacture
journal contribution
posted on 2021-09-20, 14:19 authored by Maryam Shariatzadeh, Adriana G Lopes, Katie GlenKatie Glen, Andrew Sinclair, Rob ThomasRob ThomasManufacturing of cell therapy products requires sufficient understanding of the cell
culture variables and associated mechanisms for adequate control and risk analysis.
The aim of this study was to apply an unstructured ordinary differential equationbased model for prediction of T-cell bioprocess outcomes as a function of process
input parameters. A series of models were developed to represent the growth of
T-cells as a function of time, culture volumes, cell densities, and glucose concentration using data from the Ambr®15 stirred bioreactor system. The models were sufficiently representative of the process to predict the glucose and volume provision
required to maintain cell growth rate and quantitatively defined the relationship
between glucose concentration, cell growth rate, and glucose utilization rate. The
models demonstrated that although glucose is a limiting factor in batch supplied
medium, a delivery rate of glucose at significantly less than the maximal specific consumption rate (0.05 mg 1 ? 106 cell h1
) will adequately sustain cell growth due to a
lower glucose Monod constant determining glucose consumption rate relative to the
glucose Monod constant determining cell growth rate. The resultant volume and
exchange requirements were used as inputs to an operational BioSolve cost model to
suggest a cost-effective T-cell manufacturing process with minimum cost of goods
per million cells produced and optimal volumetric productivity in a manufacturing settings. These findings highlight the potential of a simple unstructured model of T-cell
growth in a stirred tank system to provide a framework for control and optimization
of bioprocesses for manufacture.
Funding
FUTURE TARGETED HEALTHCARE MANUFACTURING HUB
Engineering and Physical Sciences Research Council
Find out more...History
School
- Mechanical, Electrical and Manufacturing Engineering
Published in
Biotechnology ProgressVolume
37Issue
6Publisher
WileyVersion
- VoR (Version of Record)
Rights holder
© The authorsPublisher statement
This is an Open Access Article. It is published by Wiley under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/Acceptance date
2021-08-25Publication date
2021-08-28Copyright date
2021ISSN
8756-7938eISSN
1520-6033Publisher version
Language
- en