Power and fluid stress in disposable square stirred tank to streamline pharmaceutical process development

Single-use systems have quickly become a standard in biopharmaceutical manufacturing due to their superior operational efficiency, flexibility and cost-effectiveness. Despite their recent and intensive use, disposable stirred tanks are not fully understood and require further characterization. Single-use square stirred tanks may exhibit unusual power consumption that may impact drug substances and drug product critical quality attributes. In this work, we use torque measurements and particle image velocimetry to validate a Computational Fluid Dynamics model designed to elucidate the fluid dynamics in a transparent replica of the Flexel® LevMixer® 50 L. Using the validated model and exploiting the renormalization group k-ε two filling-volume-dependent behaviors were identified: (i) the Swirling flow regime, characterized by low power consumption per unit volume, and (ii) the Engulfed flow regime, which requires significantly higher power. For both regimes, fluid stress induced by the mechanical agitation from the impeller is thoroughly analyzed for intensity and frequency. A strong correlation between fluid stress and power consumption is demonstrated, with implications for pharmaceutical process development involving stress-sensitive drug substances and products. These findings, which correlate power consumption with fluid stress, can streamline drug development in the pharmaceutical industry and potentially support future development of new process analytical technologies to better control drug substance and drug product quality attributes.