The displacement of product with water is the first cleaning step after each filtration phase and entails considerable product losses due to the formation of a mixed phase. In this study, we show that the volume of the mixed phase is a function of the feed volume flow and the transmembrane pressure during the filtration of reconstituted protein dispersions with spiral wound membranes equipped with different feed spacers. Thus, the simultaneous consideration of the filtration and the displacement step is required to improve the overall process performance. Applying the response surface methodology (RSM) to experimental data collected according to a statistical design of experiments (DoE), we created empirical models. These allow the identification of optimal operating points by means of desirability functions.