Seamless Integration Of Glucose Control Using Raman Spectroscopy In CHO Cell Culture

By Célia Sanchez, Laure Pétillot, Fabrice Thomas, Charlotte Javalet

In the context of Process Analytical Technologies (PAT) implementation in the biopharmaceutical industry, Quality by Design (QbD) is being developed and widely implemented and used. In upstream processes, one compound of great interest to monitor is glucose, and specifically, being able to control its concentration during the process. Such a monitoring leads to process quality improvement, including glycosylation of the product of interest. In this study, a Raman analyzer has been successfully used to implement a feedback control loop in a CHO cell culture based on glucose concentration. The feedback control loop implied a direct OPC UA connectivity between the analyzer and the bioreactor control system The culture was fed with a complex feed containing glucose. As a result, glucose concentration was maintained steady for three days. The process performance remained similar to the ones of regular fed batch cultures and a noteworthy decrease in lactate production was observed. The process was completely automated for glucose concentration management and did not require any human intervention throughout the process.