Dynamic modelling, simulation and economic evaluation of two CHO cell-based production modes towards developing biopharmaceutical manufacturing processes

Haruku Shirahata, Samir Diab, Hirokazu Sugiyama, Dimitrios Gerogiorgis

Research output: Contribution to journalArticlepeer-review

Abstract

Chinese Hamster Ovary (CHO) cells are widely used in fermentation towards biopharmaceutical manufacturing. The present paper presents dynamic mathematical models of two different CHO culture modes: one batch mode for the production of interferon, and one perfusion mode for the production of a monoclonal antibody (mAb). The dynamic models have been used for simulating cell, substrate, by-product and product concentration trajectories, which have been compared against previously published experimental results. A sensitivity analysis of both models has been conducted, in order to analyse the relative importance of operating parameters towards biopharmaceutical process design. An economic analysis has also been subsequently performed: time and net present cost for given target capacities have been evaluated, using the validated dynamic models for the batch and perfusion modes. Economic trends have been discussed for variable initial concentration of viable CHO cells to be used in bioreactors: the latter has been recognized as the most sensitive model parameter for both culture modes.
Original languageEnglish
JournalChemical Engineering Research and Design
Early online date29 Jul 2019
DOIs
Publication statusE-pub ahead of print - 29 Jul 2019

Keywords

  • Monoclonal antibody (mAb)
  • perfusion culture
  • Monod equation
  • process design
  • economic evaluation
  • biopharmaceutical manufacturing

Fingerprint

Dive into the research topics of 'Dynamic modelling, simulation and economic evaluation of two CHO cell-based production modes towards developing biopharmaceutical manufacturing processes'. Together they form a unique fingerprint.

Cite this