Using In-Situ Raman Spectroscopy to Determine Real-Time Growth and Metabolic Profiles During a Mammalian Cell Culture Process

Abstract Title: Using in-situ Raman spectroscopy to determine real-time growth and metabolic profiles during a mammalian cell culture process

Abstract Body:

Spectroscopic methods represent an innovative scheme for the analysis of in vitro processes. Raman spectroscopy offers significant advantages over other spectroscopies for bioprocess monitoring and was evaluated as a means of quantifying chemical changes in a dynamic Chinese Hamster Ovary (CHO) cell culture environment. Chemometric analyses of bioprocess data were carried out in accordance with process analytical technology (PAT) trends utilized previously in other industries. Partial least squares (PLS) calibration models were developed from offline reference standards and in-line Raman data for a specific CHO cell culture process. In the interest of rapidly demonstrating feasibility of Raman as a PAT tool for biologics manufacturing, the modeling process was expedited through the use of an automated sampling system. The autosampler provided high quantities of calibration and validation set samples from a limited number of bioreactor batches. High-quality quantitative results were obtained for glucose, lactate, glutamine, glutamate, ammonium, osmolality and viable cell density. Raman models were developed and validated at both 200L and 3L bioreactor scales. Furthermore, a combined model using both 200L and 3L data sets was successfully developed. This talk will cover methods used to generate Raman models for in-line monitoring of mammalian cell culture processes, discuss the challenges of using and implementing Raman spectroscopy, and review the data and results generated to date.