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A novel approach for non-invasive continuous in-line control of perfusion cell cultivations by Raman spectroscopy

  • Continuous manufacturing is becoming more important in the biopharmaceutical industry. This processing strategy is favorable, as it is more efficient, flexible, and has the potential to produce higher and more consistent product quality. At the same time, it faces some challenges, especially in cell culture. As a steady state has to be maintained over a prolonged time, it is unavoidable to implement advanced process analytical technologies to control the relevant process parameters in a fast and precise manner. One such analytical technology is Raman spectroscopy, which has proven its advantages for process monitoring and control mostly in (fed-) batch cultivations. In this study, an in-line flow cell for Raman spectroscopy is included in the cell-free harvest stream of a perfusion process. Quantitative models for glucose and lactate were generated based on five cultivations originating from varying bioreactor scales. After successfully validating the glucose model (Root Mean Square Error of Prediction (RMSEP) of ∼0.2 g/L), it was employed for control of an external glucose feed in cultivation with a glucose-free perfusion medium. The generated model was successfully applied to perform process control at 4 g/L and 1.5 g/L glucose over several days, respectively, with variability of ±0.4 g/L. The results demonstrate the high potential of Raman spectroscopy for advanced process monitoring and control of a perfusion process with a bioreactor and scale-independent measurement method.

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Metadaten
Author of HS ReutlingenRebner, Karsten
URN:urn:nbn:de:bsz:rt2-opus4-36382
DOI:https://doi.org/10.3389/fbioe.2022.719614
ISSN:2296-4185
Erschienen in:Frontiers in Bioengineering and Biotechnology
Publisher:Frontiers Media
Place of publication:Lausanne
Document Type:Article
Language:English
Year of Publication:2022
Tag:CHO perfusion process; Raman spectroscopy; automated glucose control; continuous manufacturing; process analytical technologies (PAT); quality by design (QbD)
Volume:10
Page Number:11
First Page:1
Last Page:11
Article Number:719614
DDC classes:570 Biowissenschaften, Biologie
Open Access?:Ja
Licence (German):License Logo  Creative Commons - CC BY - Namensnennung 4.0 International