In recent years, the biopharmaceutical industry, as one of China’s strategic emerging industries, has witnessed a sustained and rapid expansion of its market scale. Ensuring the sterility assurance of pharmaceutical products has become one of the critical challenges facing pharmaceutical manufacturers. As the mainstream sterilizing-grade filtration product, the integrity, safety, and sterilizing performance of sterilizing-grade filters are indispensable elements in process validation.
What is integrity testing?
Integrity testing is a necessary qualification method for sterilizing-grade filtration processes to ensure the safety of the filtration process. Through integrity testing, one can verify the inherent integrity of the filter itself and the correct installation of the process, ensuring that the installed filter meets the standards provided by the manufacturer, and also confirming the leak-tightness of the filtration system.
What are the methods of integrity testing?
Integrity testing encompasses both destructive and non-destructive methods. Data from destructive and non-destructive tests must be correlated to establish the user’s integrity test acceptance criteria.
Destructive Testing
Performing a bacterial challenge test in accordance with ASTM F838-15 is the optimal method for determining the bacterial retention capability of sterilizing-grade filters. However, because this test introduces a high concentration of challenge microorganisms, the filter cannot be cleaned and reused; hence, it is termed a destructive test. As the gold standard for bacterial retention testing, manufacturers should typically perform sampling inspections on filter membranes and filter housings during the production process.
Non-Destructive Testing
Due to the limitations of destructive testing, users typically employ non-destructive alternative methods for integrity testing of sterilizing-grade filters. Commonly used methods include: bubble point test, diffusion test, and water intrusion test. The frequently mentioned diffusion flow test, pressure hold test, and pressure decay test, due to their similar principles, all belong to the category of diffusion tests.
Why perform integrity testing?
1. Ensure filter integrity and correct installation: Through integrity testing of the filter, one can effectively detect whether the filter has holes, cracks, or other defects to ensure filter integrity. Simultaneously, it can verify whether the filter is installed correctly, avoiding filtration failure caused by installation errors.
2. Verify filter performance: By comparing the filter’s performance in integrity testing with its performance under actual operating conditions, one can verify whether the filter meets the standards provided by the manufacturer. This helps ensure filter performance and quality to meet process requirements.
3. Detect the leak-tightness of the filtration system: Integrity testing can also detect the leak-tightness of the entire filtration system, including filter connections and other related components. Testing can identify potential leaks or poor sealing, thereby ensuring the leak-tightness and safety of the entire filtration system.
4. Meet regulatory and audit requirements: Conducting integrity testing is a requirement of regulations and audit bodies in various countries. These regulations and audits may involve pharmaceuticals, food, electronics, and other sectors to ensure product safety during production, storage, and use.
When to perform integrity testing?
Post-Use
From the perspective of regulatory requirements and testing objectives, the requirements for post-use testing are highly consistent: as integrity testing is a critical step in sterility assurance for sterilizing filtration, testing should be performed immediately after the filter is used.
Additionally, attention should be paid to adopting in-situ testing whenever possible to better assess the integrity of the entire filtration system. If in-situ testing is not feasible due to operational constraints, the filter should remain within the housing and be removed as an assembly for testing, rather than disassembling the filter individually before testing.
Pre-Use
Pre-use testing comprises two stages: pre-sterilization and post-sterilization.
In both China and the United States, the requirements for testing at these two stages stipulate that users should determine the necessity based on scientific risk assessment. In contrast, the European Union mandates that integrity testing should be performed post-sterilization and pre-use.