Process analytical technology (PAT) promises to revolutionize manufacturing of biopharmaceuticals, enabling dynamic control of critical process parameters for tuning critical quality attributes.  Raman spectroscopy is one such PAT tool that allows for real-time monitoring of key nutrient concentrations in bioreactors.  Beyond passive measurement, Raman spectroscopy can also be used to actively control nutrient concentrations to a setpoint by continuous feeding as part of a feedback control loop.  The metabolic effects of controlling glucose or lactic acid at a setpoint rather than bolus feeding could lead to better direct control over critical quality attributes, such as glycosylation.  Using Raman spectroscopy in this manner, we controlled lactic acid and glucose to various setpoints for cultures of a mAb-producing CHO cell line in 3 L bioreactors.  Continuous lactic acid feeding resulted in a significant reduction in ammonia and CO<sub>2</sub> levels in the culture.  In terms of product quality, the mAb produced in the culture with lactic acid feeding had a higher degree of galactosylation compared to mAb produced in the control culture.  Overall, we demonstrated that Raman is not only a powerful tool for bioreactor process monitoring, but can also be implemented as part of a broader strategy to control mAb glycosylation.<br/>

You canÕt tuna fish, but can you tuna glycosylation?:  Raman as a PAT tool for product quality control

2019 Spring National Meeting

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