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

摘要

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 (IFN)-gamma, 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 different operating parameters towards biopharmaceutical process design. An economic analysis has also been subsequently performed: production 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 are discussed for variable initial concentration of viable CHO cells to be used in bioreactors: the latter has been recognised as the most sensitive model parameter for both culture modes. (C) 2019 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.