In biopharmaceutical manufacturing, every batch must meet exacting standards, driving manufacturers to constantly understand their processes better and eliminate variability that could compromise product safety. This pursuit is guided by Quality by Design (QbD) principles—ICH guidelines1 that regulatory agencies like the FDA and EMA have embraced as best practice for pharmaceutical development.2
QbD's premise is simple: build quality into the product from the ground up, not test it in at the end.2 This strategy involves understanding and controlling critical process parameters (CPPs) that influence product quality, then measuring critical quality attributes (CQAs) in real-time using Process Analytical Technology (PAT) that brings laboratory-grade analytics directly to the production floor.2
Traditional post-production batch QC testing has a costly flaw: discovering problems after manufacturing often means costly re-work or complete product loss.2 However, PAT—any technology enabling in-line, on-line, or at-line real-time monitoring—flips this script by alerting manufacturers to issues while there's still time to adjust processes and safeguard product quality.3 Real-time monitoring enables faster development, optimizes efficiency and cost-effectiveness, and generates data supporting regulatory submissions. Recent PAT advancements are positioning the technology for significant growth and are expected to drive the transition from batch processing to continuous manufacturing, bringing the industry closer to real-time quality assurance and faster product release.
Measuring product quality requires multiple analytical methods—no single parameter can provide comprehensive CQA monitoring.3 This complexity is particularly challenging in downstream processing, the critical phase where target molecules are extracted and purified. With purification costs often exceeding upstream manufacturing and accounting for up to 80% of production expenses, optimizing this phase is essential for cost control.3
PAT innovations are making downstream processing more efficient and cost-effective.3 Spectroscopy provides quantitative and qualitative information about multiple analytes simultaneously, while chromatography identifies CQAs like charge variants, size variants, and glycosylation patterns. Biosensors monitor binding properties, biomolecular interactions, concentrations, aggregates, and impurities in real-time. Perhaps most promising are intelligent manufacturing systems that combine these data streams with AI/ML capabilities, creating smarter, more responsive production processes.
AGC Biologics is at the forefront of PAT implementation for real-time monitoring and optimization of downstream processing operations. Our recent case study demonstrated how mid-infrared (MIR) spectroscopy enables accurate, real-time, in-line monitoring of an IgG4 monoclonal antibody product and all excipients during ultrafiltration/diafiltration (UF/DF).4
The results were impressive: MIR maintained 95% accuracy when compared to the reference method. Notably, our scientists could monitor excipient levels during buffer exchange to track diafiltration progress, achieving accuracy within +1% for in-line trehalose measurement compared to known concentrations. This level of precision demonstrates how PAT can deliver laboratory-quality results directly on the production floor.
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Want to learn more about PAT?
Read our full case study “Unlocking the Power of Process Analytical Technology (PAT): Elevating Downstream Process Development with Real-Time Data Monitoring” to learn about our PAT-based techniques in action
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