(5e) Using In-Situ Raman Spectroscopy to Determine Real-Time Growth and Metabolic Profiles During a Mammalian Cell Culture Process | AIChE

(5e) Using In-Situ Raman Spectroscopy to Determine Real-Time Growth and Metabolic Profiles During a Mammalian Cell Culture Process

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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.