(540g) Invited Talk: From Science-Based Modeling to Regulatory Readiness: A Qualified Hybrid Computational Framework for Biopharmaceutical Mixing

Mixing is a critical unit operation in biopharmaceutical manufacturing, influencing homogeneity, shear exposure, and ultimately product quality. To address this complexity efficiently, we developed a hybrid modeling toolkit that integrates high-fidelity Computational Fluid Dynamics (CFD) simulations with Machine Learning (ML)-based surrogate models. This mixing analysis framework enables on-demand predictions of blend time, shear stress, and vortexing across diverse equipment—ranging from stirred tanks and impulse mixers to UF/DF units and shake flasks.

To ensure the model credibility frim a regulatory point of view, the mixing tool has been qualified through a comprehensive, risk-based assessment aligned with regulatory standards (ASME V&V, FDA, and ICH Q8–Q11). A mock submission was presented to the European Medicines Agency Quality Innovation Group (EMA QIG) and included how the mixing tool risk classification shapes its regulatory support level.

This keynote will share technical and regulatory learnings from developing, deploying, and qualifying the mixing tool—highlighting its use in process optimization, scale-up, and submission strategy. By linking modeling to risk and control, the mixing tool illustrates a path from digital innovation to regulatory acceptance.