Real Time Monitoring of Bioprocess and Beyond – A Process Analytical Perspective

Presented by Dhanuka Wasalathanthri & Julia Ding at Bristol Myers Squibb A significant attention and interests have been granted towards developing an analytical paradigm with unprecedented capabilities of real time monitoring of process in biopharmaceutical development space in the past decade. The core requirement for real time analytics involves Process Analytical Technology (PAT), a system for designing, analyzing, and controlling manufacturing through real time monitoring of critical quality and performance attributes to ensure the final product quality. Regulatory agencies including U.S. Food and Drug Administration endorse the utility of PAT, and embrace the integration of novel analytical technologies for process monitoring. Our PAT landscape for process monitoring during biologics development features broad spectrum of technologies including chromatography, spectroscopy & chemometrics, sensors and mass spectrometry for inline and online analysis by integrating into upstream and downstream unit operations through automated aseptic sample preparation or proprietary flow cell sensors for real time acquisition of analytical data. The roadmap for successful implementation of PAT tools entails strategic identification of critical quality attributes, and critical control points of the bioprocess for efficient and smarter development with reliable understanding of the capabilities and limitations of the analytical technologies. Our vision includes the integration of automated-data processing, visualization, and feedback control capabilities for seamless process control. Mechanistic modeling, machine learning and deep learning techniques are utilized to deep-dive in to the analytical data, prediction and for more holistic understanding of the process. Accurate process understanding and control will enable the development of the process through quality by design (QbD) for more sustainable manufacturing of biopharmaceuticals.