Chapter 22: Development and Scale-Up of the Mixing Process for Biopharmaceuticals

Hydrodynamics of stirred vessels used in various biopharmaceutical processing unit operations affect many important process and product attributes. Hence, reliable process scale-up requires careful characterization of the mixing performance, which can be impacted by fluid properties, operating parameters, and geometric considerations. Here we begin with a discussion of the merits and limitations of empirical correlations and platform approaches that can be applied to traditional mixing systems. More advanced approaches including first-principle modeling coupled with model-guided experiments are then described, which are capable of providing a fundamental, process-specific understanding in more complex, shear-sensitive, or biphasic mixtures. Appropriate application of these tools in the design and scale-up of biomolecule processes enables more robust process performance and reproducible product attributes.