Abstract
NIR spectroscopy is a non-destructive tool for in-situ, on-line bioprocess monitoring. One of its most frequent applications is the determination of metabolites during cultivation, especially glucose. Previous studies have usually investigated the applicability of Near Infrared (NIR) spectroscopy at one bioreactor scale but the effect of scale up was not explored. In this study, the complete scale up from shake flask (1 L) through 20 L, 100 L and 1000 L up to 5000 L bioreactor volume level was monitored with on-line NIR spectroscopy. The differences between runs and scales were examined using principal component analysis. The bioreactor runs were relatively similar regardless of scales but the shake flasks differed strongly from bioreactor runs. The glucose concentration throughout five 5000 L scale bioreactor runs were predicted by partial least squares regression models that were based on pre-processed spectra of bioreactor runs and combinations of them. The model that produced the lowest error of prediction (4.18 mM on a 29 mM concentration range) for all five runs in the prediction set was based on the combination of 20 L and 100 L data. This result demonstrated the capabilities and the limitations of an NIR system for glucose monitoring in mammalian cell cultivations.
Highlights
Chinese hamster ovary (CHO) cells are the mammalian workhorse of the biopharma industry
That the elements of the cultivation technology and Near Infrared (NIR) instrument were similar for all experiments, the shake flask spectra were significantly different from bioreactor cultivations, according to the principal component analysis (PCA) model
Results of glucose concentration monitoring by NIR spectroscopy during a complete scale up of a mammalian cell cultivation process were presented and discussed
Summary
Chinese hamster ovary (CHO) cells are the mammalian workhorse of the biopharma industry They are extensively used for recombinant protein production, especially monoclonal antibodies (mAb) [1, 2]. Pastoris) but complex protein molecules, which have several post-translational modifications to function properly as a medicine, require mammalian host cells [3]. These cells are more sensitive to cultivation parameters than the above-mentioned bacterial or yeast cells because they do not possess a cell wall that. Strict monitoring and control of the cultivation parameters is mandatory to ensure process reproducibility and the desired product quality [4]. The parameters that are proven to affect the critical quality attributes (CQAs) of the protein product are the critical process parameters (CPPs) that have to be monitored and controlled during the process to ensure the desired product quality
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