Selecting Components for the Lyophilization Process
Lyophilization removes water from a drug product through three phases: freezing, primary drying or sublimation, and secondary drying or desorption. To begin the process, the drug product is frozen and then placed under a vacuum, which allows the ice to change from solid to vapor without passing through a liquid phase.
The process typically includes the following phases:
- Dissolving the drug and excipients in a suitable solvent, such as water for injection
- Sterilizing the solution
- Filling individual sterile containers
- Partially stoppering the containers under aseptic conditions
- Transporting the partially stoppered containers to the lyophilization chamber
- Freeze-drying the solution
- Applying a vacuum and/or heating the shelves of the lyophilization chamber to evaporate the water from the frozen state
- Final stoppering of the vials
According to the FDA, lyophilization has many advantages, including enhanced stability, extended shelf-life while maintaining potency, increased resistance to changes in temperature, and rapid and easy dissolution of the reconstituted drug product. However, the process requires increased handling and processing time, and can be complex and costly – particularly if the materials selected for the primary container are not consistent or interfere with the lyophilization process. The proper selection of a lyophilization stopper manufactured with Quality by Design (QbD) principles can help to ensure that the freeze-drying process moves smoothly while preventing and/or reducing potential contamination from the atmosphere or the container closure system.