Sterile Filtration: What You Need To Know About Integrity Testing
Integrity testing, how to validate your sterile filtration, and be confident in the results
8. Juli 2021
In the first of our four-part “Filtration Nation” series, we discussed the importance of prefiltration and how it’s a frequently overlooked step but a critical driver of success in any sterile filtration protocol. In part 2 this week, we turn our focus to understanding integrity testing for sterile filtration.
Once you have set up a protocol that incorporates one or more sterile filtration steps, either in a research/development/laboratory setting or in a manufacturing environment. It is critical to undertake integrity testing to challenge the system and confirm that the sterile filtration is working, and your process is compliant. Indeed, in any pharmaceutical, food product, or other regulated environment this type of validation is mandatory.
The type of integrity testing most users will be familiar with is non-destructive testing, normally undertaken as part of the validation activities for any new sterile filtration process, and often repeated at pre-defined intervals to ensure that a filter continues to provide sterile filtration. Non-destructive, meaning that after testing is complete, the equipment you tested can still be used for its intended purpose. The type of testing you choose is dependent on the type of filter membrane being used (hydrophilic or hydrophobic) and the scale of your filtration. For example, more testing methods are available for larger-scale processes with higher flow rates, and there are more options available for hydrophobic membranes.
Hydrophilic and hydrophobic membrane testing
In a recent scientific brief, Pall’s Director of Scientific Laboratory Services, Joseph Baaklini, goes into much greater detail on how to select the best integrity test for your specific circumstances, as well as providing links to datasheets and other useful resources. The different testing methods range from bubble point test, forward flow tests, and pressure hold/pressure-decay tests for hydrophilic membranes. Users wishing to test hydrophobic membranes can leverage the same three tests as described above, plus a fourth method can be performed called the water breakthrough/water intrusion test.
Basically, the naturally hydrophobic PTFE (Polytetrafluoroethylene) membrane resists water penetration. However, water can be forced through the membrane under high pressures. The pressure required to force water through (the water breakthrough point) directly correlates to the pore size of the membrane. This relatively simple and reproducible test takes only a minute to run and can be performed either in situ or in the laboratory.
Validating the tests. Destructive testing
How can we be sure the non-destructive testing is accurate? The key to this lies with the manufacturer, which is a good thing because the destructive testing that they need to undertake in order to validate the product claims is far more arduous. Destructive testing involves challenging the membrane under avariety of conditions with actual live microorganisms and ensuring that the filter is consistently able to remove them. The results of these destructive tests are correlated to the results of the non-destructive testing, and it is this correlation that allows the end-user to test their membrane using sterile media such as air, water, or other sterile fluids and have confidence in the result. After all, in many manufacturing environments, e.g., injectable pharmaceutical manufacturing, the sterility of the product can have life or death consequences.
You can find this Scientific Brief on integrity testing on our Scientific Resource Hub, along with a host of other concise, highly focused briefs dealing with all the major issues, concerns, and challenges of filtration. Stay tuned for Part 3 where we will further discuss sterile filtration and differential pressure monitoring.