PAT: Build Quality into Biopharmaceutical Process
with Real-Time Monitoring and Control
Process Analytical Technology (PAT) ensures quality in biopharmaceutical manufacturing by monitoring and controlling processes in real-time. It utilizes analytical tools to develop manufacturing processes that accommodate material and equipment variability. Once critical process parameters (CPPs) impacting critical quality attributes (CQAs) are identified, analytical methods are employed to monitor and control CPPs, maintaining them within the desired design space. This approach integrates quality by design (QbD) principles into the process rather than relying on product testing only in the end.
In-Line & Real-Time Raman Monitoring
Raman spectroscopy is among the many tools used in PAT implementation. It enables the determination of chemical composition and molecular structure in a non-destructive and reproducible manner, eliminating the risk of losing chemical information due to degradation, instability, or sample preparation. For example, the technique can be used to monitor cell culture CPPs such as glucose, lactate, cell density, and ammonium, as well as CQAs such as protein titer, glycosylation, and aggregation. Analysis is performed by insertion of a probe into the process along with other widely used sensors; as such, it enables real-time monitoring and automation of the process, and also eliminates the need to collect samples to send to the quality control (QC) lab for analysis.
Compared with traditional off-line analytical methods such as a cell culture multitest analyzer, cell viability analyzer or HPLC, Raman spectroscopy offers clear advantages for both upstream (USP) and downstream (DSP) processes including:
- Multi-attribute monitoring with a single probe
- Implementation of an automatic feeding strategy during cell culture growth
- Complete chemical and biological information collected in a single spectrum
- Access to real-time and in situ measurements
- Non-destructive analysis
- Easy implementation using an in-line probe
Specifically designed for the bioprocessing industry, the ProCellics™ Raman Analyzer is an easy-to-use Process Analytical Technology (PAT) platform used to monitor USP and DSP bioprocesses in-line and in real-time, from Process Development to Manufacturing.
It ensures better process understanding and enables the implementation of an automated process control strategy. In addition, the platform contributes to time savings, provides operator flexibility, and reduces contamination risk and batch failures compared to manual sampling.
The ProCellics™ Raman Analyzer is available in two configurations, fully adaptable to manufacturing requirements, to address a range of monitoring needs, from process development to manufacturing:
The single channel unit enables the monitoring of cultures with a single probe. The package includes a base unit with a 785 nm laser, one probe, accessories, and an all-in-one computer including Bio4C® PAT Raman Software.
The multi-channel unit enables the monitoring of up to four cultures in parallel within the same system footprint. The package includes a base unit with a 785 nm laser, a multi-channel unit with four probes, accessories, and an all-in-one computer including Bio4C® PAT Raman Software.
An advanced probe tube, combined with specific software features, is available to counter the effect of light interference, eliminating the need to shield the bioreactor from light rays.
It strengthens the scalability of Raman technology across various unit operations, allowing for seamless transitions from single-use to multi-use systems, and from different scales between process development and manufacturing.
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Related Resources
- Datasheet: ProCellics™ Raman Analyzer with Bio4C® PAT Raman Software
Specifically designed for the bioprocessing industry, ProCellics™ Raman Analyzer with Bio4C® PAT Raman Software enables you to perform in-line and real-time measurement of CPPs and CQAs, from process development to manufacturing.
- Article: Seamless Integration of Glucose Control in CHO Culture Using Raman Spectroscopy
This page describes the use of a ProCellics™ Raman Analyzer with Bio4C® PAT Raman Software to implement a feedback control loop in a CHO cell culture process to monitor glucose concentration and enable maintenance of stable glucose levels without the need for manual intervention.
- Application Note: In-line Real-time Monitoring of CHO Cell Culture Process Parameters Using Raman Spectroscopy
Cell culture processes are complex and highly variable and yet only a handful of key parameters such as temperature, pH, and dissolved oxygen (DO) are typically controlled in real time.
- Application Note: Implementation of Raman Spectroscopy for In-line Monitoring of CPPs of CHO Cell Perfusion Cultures
This application note introduces a case study for the implementation of a Raman spectroscopy soft-sensor for in-line and real-time monitoring of critical process parameters (CPP) in mammalian perfusion cell cultures.
- Application Note: Seamless Integration of Glucose Control Using Raman Spectroscopy in CHO Cell Cultures
Process analytical technology (PAT) and quality by design (QbD) are used in the biopharmaceutical industry to ensure quality is designed into a process and to achieve innovative quality improvements.
- Article: Influence of Cell Specific Parameters in a Dielectric Spectroscopy Conversion Model Used to Monitor Viable Cell Density in Bioreactors
In the biopharmaceutical industry, the use of mammalian cells to produce therapeutic proteins is becoming increasingly widespread. Monitoring of these cultures via different analysis techniques is essential to ensure a good quality product while respecting good manufacturing practice (GMP) regulations.
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