Lyophilizer Qualification Overview
A lyophilizer is used for the process of freeze-drying a product or solution to remove water. Reducing the water content reduces weight and increases product stability. This allows product to be stored for longer periods of time and to be shipped and stored with relative ease.
The parameters critical to the process are temperature and pressure, or vacuum. The product is first frozen (typically in temperatures of approximately -40ºC to -50 ºC), then pressure is reduced while temperature is increased, causing sublimation of the water content. Critical parameters are usually monitored for every cycle performed to ensure adequate water removal, but lypohilizers also require routine validation and maintenance
There are several aspects to the qualification of a lyophilizer that need to be considered. Qualification typically includes thermal mapping of the chamber shelves, a condenser cool-down test, a vacuum test to check vacuum pump efficiency, a vacuum leak test to check seal integrity, and qualification of the steam supply and Steam-in-Place system
Depending on the specific application, lyopilizers can operate as batch dryers or continuous dryers. Batch dryers are used for bulk drying, where product is placed in vials or trays with rubber stoppers designed specifically to allow vapor to escape. Ellab offers several solutions for the qualification of these dryers:
- E-Val Pro, with various thermocouples offered.
- TrackSense Pro X, Pro XL, Compact Ultra X sensors capable of withstanding lyophilzation temperatures, with Smart Flex temperature sensors offering an accuracy of ±1ºC over the range of -40ºC to 140ºC.
- TrackSense Pro X Vacuum sensor, with a range of 0.0001 mBar to 1,000 mBar (-60ºC to 80ºC)
- LYO 28, which will hold TrackSense Pro PTFE flex sensors in the exact position required for accurate readings inside the freeze drying vials during temperature mapping studies.
- Lyo Shuttle, a fixture for lyophilizer vial loading systems. Designed to hold vials of various sizes with a Pro-X logger to ensure proper sensor placement throughout the lyophilization cycle.
As the seal integrity is crucial during lyophilization and SIP cycles, it is highly recommended that wireless dataloggers are used for their qualification. The available SKY option allows for the live transmission of data during the studies, which is important during processes as exact as freeze drying and sterilization.
Continuous freeze dryers are designed to perform vial drying, filling, loading and unloading of product. This automates the automatic and sterile manufacturing of product with SIP sterilization occurring between batches. As such, wireless dataloggers must be used for this application. The SIP system will require multi-channel flex sensors.
In addition to the multitude of validation solutions offered, Ellab’s validation staff can assist with the qualification of your lyophilizer from protocol development through report delivery.
Standards and Guidelines
- ISO 13408-3 – Offers guidelines and guidance on the process and procedures for the development and validation of manufacturing processes for aseptically processed pharmaceuticals, with specific regards to lyophilization.
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