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PAT: Build Quality into Biopharmaceutical Process

with Real-Time Monitoring and Control

HomeIntegrated OfferingsBiopharma 4.0Process Analytical Technology (PAT)In-Line & Real-Time Raman Monitoring

 

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. This optical analytical technique identifies molecules by their unique fingerprint and is very well suited for biopharmaceutical processes: Thanks to its high molecular specificity and minimal disruption from water, it can monitor multiple parameters simultaneously even in complex, aqueous biopharmaceutical solutions. Raman spectroscopy 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, Raman technology 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. However, if preferred by the user or mandated by the specific process set-up, it offers the option for on-line, at-line or off-line measurements as well.

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:

Installation of an in-line Raman probe into a 3 L bioreactor. This probe is connected through a cable to the ProCellics™ Raman Analyzer, itself connected to a computer on which runs the Bio4C® PAT Raman Software which analyzes the data collected by the 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, from process development to manufacturing, for qualitative and quantitative analysis. 

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. As a result, it empowers the user to navigate cell culture processes with confidence.

ProCellics™ Raman Analyzer single channel unit enables the monitoring of cultures with a single probe.

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.

ProCellics™ Raman Analyzer multi-channel unit enables the monitoring of up to four cultures in parallel within the same system footprint.

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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