Process Analytical Technology

In current biotherapeutic manufacturing strategies, “the process is the product” means that strict control of process parameters such as pH, temperature, and feedstock consumption is required to guarantee product quality. Only at the end of the process can QC procedures check the critical quality attributes (CQAs) that define product quality. Hence, most PAT instruments monitor process conditions rather than product attributes.

Real-time multi-angle light scattering (RT-MALS) is a novel PAT application of light scattering, that directly determines the molecular weight of mAbs and other therapeutic biomolecules. It is particularly sensitive to the appearance of aggregates and contaminant particles. Using the ultraDAWN™ RT-MALS instrument, in-line or on-line with purification and other process steps, production staff can speed up and optimize process development with immediate feedback on the impact of process variations and deviations. UltraDAWN measures another attribute, the average radius, for virus-like particles and other biomolecular complexes with diameters above 25-30 nm.

After developing the process, the ultraDAWN may be left on-line. Its accompanying software, OBSERVER™, integrates with an OPC-UA environment for automated and/or GMP operation. OBSERVER can be programmed to trigger the system to react to deviations from the allowed molar mass range due to aggregation, or to shut down a reaction once the endpoint has been reached.