Figure 4.

%soluble aggregation of rHSA (3 mg/ml) measured by SEC as a function of residence time (indicated on the right axis) at various process conditions. Only dimers were detected by SEC in the reconstituted rHSA samples after freeze-drying at all cooling rates. In all experiments, ice nucleation was controlled at a shelf temperature of −12°C. The shelf ramp rate post ice nucleation varied from 2.5°C/min to 1, or 0.1°C/min. For the studies of hold time and hold temperature, % soluble aggregation was measured for a 6-h hold post-ice nucleation at −12°C or −18°C. The residence time in the frozen concentrate was calculated from when the ice nucleated to when the product temperature reached −12°C. Reproduced from [79].