Particle Monitoring Requirements: Freeze Dryers

Freeze-drying is used to produce the majority of today’s dried pharmaceuticals, i.e. those compounds that require reconstitution with water prior to use. Freeze-drying or lyophilization refers to the only manner in which water can be removed from organic substances without damage to the cell structure and subsequent loss of volatile components. The process requires freezing the product, separating out the water as ice crystals, and then under vacuum, introducing controlled heat causing the ice to sublimate, releasing the water as a vapor. The final product is left completely dry with minimal change to the product structure, cell matrix or chemical composition. The process under which products are manufactured using the lyophilization requires a standard aseptic manufacturing filling operation, sterilization of the vials, classic filling in either open or isolator fill lines and subsequent stoppering of the final product. It is at this final stage where a freeze-dried product diverts form the classic model; the stopper is only partially closed allowing air to exit the stopper. The stoppered vials are then transferred to the lyophilizer where the freeze-drying process is run; once the cycle is complete the final closure of the stopper is performed within the machine. The product is then removed from the Lyophilizer and packaged.

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