The sterilizing grade filter on a freeze dryer is a fundamental element for maintaining sterility throughout the process of lyophilization. According to Annex 1 in the European Guidelines, the integrity of critical gas filters should be confirmed after use (1). Risk analysis could also confirm the need for testing before use because of the value of a particular product.
The water intrusion test (WIT) for hydrophobic PTFE membrane cartridges enables in situ integrity testing without the interference of contaminative wetting media (e.g., alcohol) and obviates the need for downstream manipulation. WIT measures the decay rate of a pressure level imposed upon a hydrophobic membrane surrounded by water on the upstream side. Its dependability derives from the demonstrated correlation of the test values to organism retention levels in accordance with the HIMA ASTM F-838-05 guideline (2).
WIT has been demonstrated to apply to mono membranes of expanded PTFE since 1991. It may or may not extend to other constructions. Importantly, WIT reflects the hydrophobicity of the filter and thus assesses the suitability of air filters for reuse in equipment, such as freeze dryers, autoclaves, and all other venting applications.Temperature drift may have a significant effect on the integrity test value and may result in false conformity or false non-conformity test results. To avoid this thermal impact, a thermal compensation algorithm can be used for applications (e.g., freeze dryers and autoclaves) on which an integrated WIT-system has been implemented.
This article will describe the operational qualification of the test accuracy using the thermal-compensation algorithm. Sartorius Stedim and the Global Technical Service for Secondary Technologies of GSK Biologicals qualified the test jointly on several freeze dryers (IMA Life).
Materials and methods
The following equipment and materials were used: freeze dryers (LMX33, IMA Life), hydrophobic sterilizing grade filter (Sartofluor 0.2 µm, 10 in., Sartorius), cartridge dummy (hand-made from filter cartridge components), stainless steel filter housing (Sartorius), Nitra pneumatic 4-mm diameter tubing (Nitra, AutomationDirect), needle valve for water (Swagelok), high precision scales (Sartorius Stedim), electro heating ribbon (Tibtech), and a sports timer (EA Combs).
For all accuracy trials, a standard WIT was launched from the supervisory control and data acquisition (SCADA) system on the freeze dryer using the filter dummy. The WIT involved the following steps:
All test parameters were visualized on SCADA and printed.
For the drying qualification, a real membrane cartridge was used. The detailed information in this article will be restricted to accuracy qualification and temperature-drift correction.