*3.1. Continuous Operation and Steady-State Analysis*

Along the continuous operation, quantities of the liquid phase, such as volumetric flowrate and local temperatures, were measured and, as seen in Figure 5a,b, controlled appropriately. Figure 5 also depicts the temporal evolution of the fluid density (Figure 5c), measured via the Coriolis mass flowmeter, and the D-Asn enantiomeric proportion of the liquid phase within the feed tank and at the crystallizer outlet (Figure 5d), determined via HPLC offline samples. As seen in Figure 5c,d, these measured quantities also show no discernible trends during the whole experiment. Thus, the applied operation procedure successfully prevents fluctuations or depletions of the feed concentration. Furthermore, the depleted D-Asn enantiomeric proportion at the crystallizer outlet indicates the selective removal of the seeded enantiomer due to the Preferential Crystallization.

**Figure 5.** Evolution of the saturation temperature, Tsat, crystallization temperature, Tcrys (**a**), volumetric flowrate (**b**), liquid phase density of the feed solution, ρliq (**c**), and enantiomeric proportion of the D-Asn·H2O in the liquid phase at the crystallizer outlet and within the feed tank (**d**), of Exp. 7 (C1) over time, with t = 0 indicating the initial seeding point. Spikes occurring in the flowrate and solution density courses can be attributed to air bubbles passing the Coriolis mass flowmeter (data shown are raw data without any curve treatment).

The temporal evolution of the above introduced process performance parameters, product crystal mean size, L3, standard deviation of the product crystal size distribution, sL3, and productivity, Pr, are illustrated in Figure 6 for Exp. 7. As shown in Figure 6, all process performance characteristics reached almost constant values after approximately 2 h process time. During the following 6 h operation time the mean product crystal size varies between 315 to 321 μm with a respective standard deviation between 57 and 60 μm. The calculated productivities range in the same time between 30 and 37 g/L/h, while the product purity exceeds 98% for the whole experiment.

**Figure 6.** Evolution of mean product crystal size, L3 (**a**), its respective standard deviation, sL3 (**b**), productivity, Pr (**c**), and product purity, Pur (**d**), of Exp. 7 (C1) over time, with t = 0 indicating the initial seeding point. Illustrated are the values of the process characteristics for every product withdrawal as points with their corresponding time window as line.
