Mixing of a mAb Formulation in a New Magnetically Coupled Single-Use Mixing System: Key Learnings of Preliminary Experimental and Computational Evaluation

Abstract

MilliporeSigma recently introduced a new magnetically coupled single-use mixing system (Mobius® Power MIX) for more efficient mixing of buffers and media in biopharmaceutical applications. Experimental and computational fluid dynamics (CFD) assessments were performed on the Power MIX 100 system to understand product quality impact, shear, and mixing efficiency. It was interesting to note slightly higher submicron (0.4-1 μm) and subvisible (1-54 μm) particle formation at the lower mixing speed (50 RPM) compared to higher mixing speeds (100/200 RPM). Mixing speed and time showed negligible impact on the other product quality attributes tested, including protein concentration, turbidity, general appearance, purity, and soluble aggregates. The CFD simulations provided useful information with respect to the impact of batch size (20-100 L), viscosity (2-50 cP), and impeller speed (100-300 RPM) on mixing time (mixing time ranged from 10 to 365 s) and shear (maximum shear rate was found to be localized around the impeller and it was about 30,260 s^-1, whereas the average shear rate ranged from 4 to 36 s^-1). Statistical analysis of the CFD results showed that natural-log transformation and quadratic fitting were found to be suitable statistical models to predict mixing time and shear within the design space of the parameters assessed in the present study.

Keywords: CFD; Power MIX; aggregation; mAb; mixing; mixing speed; mixing time; shear; sub-micron particles; sub-visible particles.