Development of a Raman Model for Continuous Monitoring of Detergent Viral Inactivation

Process analytical technology (PAT), such as Raman spectroscopy, has been used in a wide range of applications across many unit operations in mAb-producing processes. In continuous manufacturing (CM) processes, PAT can ensure consistent quality throughout operations by continuously monitoring critical attributes. PAT is especially useful when it can replace offline measurements of critical parameters with real-time, in-line measurements. In this study, a 785 nm Raman-based model was developed as an online measurement for the detergent concentration in a continuous viral inactivation (VI) step. In the VI step, detergent is continuously added to a concentrated bioreactor perfusate stream. The Raman flow cell was first calibrated using a bank of previously generated perfusate samples spiked to varying detergent levels to generate a PLS model with an estimated accuracy of 0.02% w/v. Later, the flow cell was directly integrated into a pilot-scale process to demonstrate real-time monitoring of the detergent addition step. The development of this Raman-based detergent measurement will help replace the need for offline analysis by generating nearly instantaneous concentration measurements. This real-time measurement will be used during processing to ensure the continuous VI step maintains a sufficient level of detergent to effectively inactivate viruses.