Mammalian cell culture is an integral part of biopharmaceutical manufacturing, but in-process monitoring strategies often lack real-time measurements. Unfortunately, the process mostly remains a highly manual low-throughput process that can increase the risk of batch contamination. Advances in process analytical technology (PAT) have surged because of industry-wide adoption of Quality by Design (QbD) principles. QbD seeks to build the quality of a product into the manufacturing process itself rather than simply relying on end-product testing. PAT plays an integral role in QbD since it can provide important metrics during the manufacturing run for bioprocess insight. These metrics not only ensure consistent product quality but can also inform strategies to increase throughput and introduce automation to build efficiency throughout the workflow.

Raman Spectroscopy

Raman spectroscopy has many advantages as a PAT tool since it is a non-invasive, non-destructive optical molecular spectroscopic method that can monitor multiple analytes simultaneously in real-time with minimal sample processing. Leveraging this technology, MilliporeSigma has developed the ProCellics™ Raman Analyzer with Bio4C™ PAT Raman Software specifically for the bioprocessing industry. This addition, provides an all-in-one compact GMP platform that is easy to use and can be implemented in biomanufacturing for real-time, in-line monitoring of critical process parameters (CPP) and critical quality attributes (CQA). The goal for implementing the ProCellics™ Raman Analyzer is to enable process optimization, enhanced control and product reproducibility. By providing automated sampling capabilities the need for manual handling is eliminated, thereby allowing for operator flexibility alongside reduced risk of contamination. In addition, access to real-time data permits the detection and immediate correction of in-process irregularities which helps to minimize batch failures and implement an automated nutrient control loop strategy.

To fully support operation, the proprietary Bio4C PAT Raman Software provides comprehensive functionality designed for bioprocess monitoring from Raman spectral acquisition, reference data association, and Raman spectral pre-processing.  Multivariant analysis for chemometric model building is supplied to facilitate real-time process monitoring of CPPs and CQAs and process batch anomalies analysis.

The entire Raman spectroscopy platform is fully supported by a team of experienced Raman technology experts, engineers and chemometric bioprocessing specialists to ensure successful implementation and use, from process development to manufacturing. The platform is suitable for GMP clean room environments, and the proximity allows convenient access to multiparameter bioreactor data for active in-process monitoring. Overall the  platform facilitates better process understanding, which ultimately can be used to improve bioprocess manufacturing efficiencies.

For more information on the ProCellics™ Raman Analyzer, please visit www.emdmillipore.com/raman-pat-platform