Advanced control in freeze-drying

The concept of modern closed-loop control was introduced for freeze-dryers in the pharmaceutical field in the early Sixties. Among various drying processes, freeze-drying stands out as the liquid, usually water, is removed at low temperature; this allows for better preservation of critical quality attributes (CQAs) of the product being processed than in high temperature drying. The freeze-drying process is composed of three stages: freezing, primary drying, and secondary drying. The operating conditions of the freeze-drying process influence not only product temperature but also the sublimation flow rate and, finally, the drying time. Several control systems were proposed in the past using the product temperature measurement as a monitoring tool. Thermocouples or resistance thermal detectors are generally used to measure the temperature of the product: the former in lab-scale apparatus as they allow a punctual measurement using thin wires, the latter in industrial-scale freeze-dryers as they are more robust, even if larger and more invasive.