Advancing Raman Calibration: Automated Data Generation, Monitoring, and Control in Multi-Parallel Perfusion Mini...

Area of Science:

• Biopharmaceutical Manufacturing
• Process Analytical Technology (PAT)
• Spectroscopy

Background:

• The biopharmaceutical industry seeks cost-effective production methods for affordable treatments.
• Process intensification, like perfusion, aims to lower costs, enhance productivity, and reduce facility size.
• Perfusion processes require advanced real-time monitoring and control due to their dynamic nature.

Purpose of the Study:

• To implement an automated data generation workflow for Raman calibration modeling.
• To demonstrate the effectiveness of Raman calibration models for monitoring perfusion cultivations.
• To assess the feasibility of a Raman-based bleed-rate control system.

Main Methods:

• Utilized a high-throughput perfusion miniature bioreactor system (Ambr 250 HT Perfusion).
• Developed an automated data generation workflow for Raman spectroscopy calibration.
• Applied Raman calibration models to monitor cell culture parameters across multiple cell lines and products.
• Compared a Raman-based bleed-rate control system with conventional cell counter methods.

Main Results:

• Successfully implemented an automated workflow for generating Raman calibration data.
• Demonstrated the efficacy of Raman models in monitoring diverse perfusion cell cultures.
• Showcased the feasibility of a Raman-based bleed-rate control strategy.

Conclusions:

• Automated Raman data generation facilitates robust calibration modeling for perfusion processes.
• Raman spectroscopy offers a powerful tool for real-time monitoring and control in biopharmaceutical manufacturing.
• Raman-based control systems present a viable alternative to traditional methods, enhancing process efficiency.