Optimization of the drug solution preparation process for a production-scale crossflow ultrafiltration system

This article describes a new approach to optimizing the drug solution preparation process for a production-scale crossflow ultrafiltration system. Equations were proposed to predict the concentration of the active ingredient and the volume of drug solution in the crossflow ultrafiltration process. These equations take into account the residual water remaining in the process line after the set-up of the ultrafiltration system, the residual drug solution remaining in the process line after ultrafiltration, and the residual Water for Injection (WFI) remaining in the process line after WFI rinsing. Because the residual water or residual drug solution varies slightly for each type of production, it was convenient to define them as preparation parameters. Using the proposed equations, testing was performed during early production in order to collect data on the crossflow ultrafiltration process, and the preparation parameters were then optimized. The concentration of the active ingredient and the weight of the drug solution (which was converted to the drug solution volume using its specific gravity) were calculated accurately with the optimized preparation parameter using the proposed equations. These results indicate that the proposed equations and method of establishing the preparation parameters are useful for a production-scale crossflow ultrafiltration system.