Numerical Characterizing of High-Viscosity Biopharmaceutical Stirred Tanks with Experimental Validation – a Regulatory Submission Strategy

Stirred tank reactors are frequently used for mixing as well as heat and mass transfer processes in chemical and biochemical engineering due to their robust operating behavior. In addition, stirred tank reactors have been intensively investigated and documented, especially in chemical process engineering [1, 2]. However, the increasing demand for higher product concentrations necessitates the use of mixing equipment capable of handling increased viscosity without damaging shear-sensitive drug products.

Advancements in computational power have significantly enhanced the use of numerical computational fluid dynamic (CFD) methods, allowing for easy and comprehensive characterization of mixing performance. However, the regulatory requirements for equipment characterization and the use of numerical methods have increased significantly, particularly for submission to FDA [3].

In this contribution, we highlight the critical need for detailed characterization studies of biopharmaceutical stirred tanks under high-viscosity conditions. By combining experimental at-scale data with numerical models, we provide a comprehensive analysis that is essential for regulatory submissions, ensuring that the mixing processes meet stringent regulatory requirements regarding product homogeneity and stability. Additionally, we share practical insights and lessons learned from recent regulatory submissions, offering valuable guidance for future applications. Furthermore, our latest findings provide deeper understanding of stirred tank performance with high-viscosity fluids, highlighting how numerical simulations can significantly enhance the efficiency and reliability of industrial mixing process characterization.

[1] Zlokarnik, M. Stirring: Theory and Practice, 2001
[2] Kraume, M., Mischen und Rühren, 2012
[3] FDA, “Assessing the Credibility of Computational Modeling and Simulation in Medical Device Submissions - Guidance for Industry and Food and Drug Administration Staff.” Center for Devices and Radiological Health. 2023