Rapid depressurization controlled ice nucleation in pharmaceutical freeze-drying

A lyophilization system for lyophilizing products inside one or more vials within a lyophilization chamber, comprising:

• a cooling mechanism adapted to cool shelves in the lyophilization chamber;
• a high pressure source adapted to pressurize the lyophilization chamber;
• a valve coupled to the lyophilization chamber and adapted to suddenly release pressure within the lyophilization chamber;
• and
• a controller adapted to:
• cool the shelves in the lyophilization chamber to a predetermined temperature;
• pressurize the lyophilization chamber with a humidified charge gas to a pressurization threshold to thereby achieving a target relative humidity level within the lyophilization chamber;
• and
• during a depressurization, suddenly release pressure within the lyophilization chamber until a depressurization threshold is reached in a predetermined amount of time up to about 4 seconds, during the depressurization, product inside one or more vials nucleate, thus leading to lyophilizing products.