Implementation Of Raman Spectroscopy For In-Line Monitoring Of CPPs Of CHO Cell Perfusion Cultures

Process Analytical Technology (PAT) is a regulatory framework initiated by the United States’ Food and Drug Administration (FDA) that encourages innovation in pharmaceutical development, manufacturing, and quality assurance. The goal of PAT is to build quality into biopharmaceutical production processes by monitoring and controlling the process in real time. Through the identification and monitoring of critical process parameters (CPP) and critical quality attributes (CQA) within a specified design space, Raman spectroscopy enables understanding of cell culture processes and improvement of product quality by real-time monitoring. Rather than measuring the quality by testing, we are incorporating quality into the design of the process, making it more robust and transparent.

Explore the development and implementation of Raman spectroscopy-based soft sensors for process monitoring of CPPs in bench scale, CHO cell, intensified seed trains (N-1). The framework presented herein combines the use of ProCellicsTM Raman Analyzer with Bio4C® PAT Raman Software for spectral acquisition, data management and process monitoring as well as the use of Bio4C® PAT Chemometric Expert Software for multivariate model development. The introduced workflow for data pre-processing and processing stages demonstrated a potential to employ soft sensors to provide effectively continuous monitoring capabilities for multiple key cell culture process parameters in intensified upstream processing.