Watlow® Technical Paper provides overview of freeze drying lyophilization

The latest Technical Paper from internationally thermal solutions leader Watlow® provides a useful overview of the freeze-drying process in life sciences and its monitoring and control challenges.

The article points out that freeze-drying, also known as lyophilization or cryodesiccation, is a high energy process that demands economical drying cycles suitable for large scale production and that the vacuum and refrigeration units need very close process automation control to prevent excess wear.

Freeze drying overview

Lyophilization is a slow batch process used in biopharma to extract dry product from an aqueous solution, producing powders that can be stored, shipped, and later reconstituted with water for use in products such as solid dose tablets and soluble solutions.

The basic process involves freezing the material, then reducing the pressure and adding heat to allow the frozen water in the material to sublimate at the water triple point condition. Thus, there are at least five vital control points: initial vacuum chamber temperature and pressure, process temperature including chamber, shelves and condenser, plus vacuum readings during freezing.

Drying complexities

The drying process is even more complex, since it must be done in stages:

• Primary (sublimation) drying: a prolonged and critical phase during which water sublimation but be slow enough not to damage the product, requiring vacuum to be held constant and a consistent temperature ramp achieved
• Secondary (absolute) drying following a Pressure Rise Test (PRT) to check the dryness by sealing the chamber and looking for pressure to increase, a final drying phase is needed to ensure absolute dryness, with product gradually brought up to or just above ambient temperature.

Finally, everything must be sterilized prior to next batch, requiring yet more control sensors and functions to monitor the action of steam or gases, such as ethylene oxide.