After using the sterilization filter, its integrity must be immediately tested and recorded using appropriate methods. Before using the sterilization filter, a risk assessment should be conducted to determine whether integrity testing should be performed and whether it should be performed before or after sterilization. When conducting integrity testing after sterilization and before use, measures need to be taken to ensure the sterility downstream of the filter. The commonly used integrity testing methods include bubble point testing, diffusion/forward flow testing, or water intrusion testing.
Disinfectants entering Class A and Class B clean areas should be sterilized through filtration or other appropriate methods. If using filtration methods for sterilization, the suitability between the disinfectant and the selected filter material should be evaluated. The filter needs to undergo integrity testing after use.
Filters used for direct contact with sterile liquids or sterile equipment surfaces should undergo integrity testing after each batch or multiple batches of continuous production are completed. For other applications, the frequency of integrity testing can be determined based on the results of risk assessment. The integrity testing of gas filters can be carried out using low surface tension liquid wetting for bubble point or diffusion/forward flow testing; Water intrusion testing can also be used. The water intrusion method can be given priority.
For redundant filtering, the main filter should be tested for integrity before use. If the integrity test of the main filter passes, the redundant filter does not need to undergo integrity testing; If the integrity test of the main filter fails, it is necessary to perform integrity testing on the redundant filters. The integrity test results of redundant filters can serve as the basis for product release. Before using the sterilization filter, a risk assessment should be conducted to determine whether integrity testing should be performed, which level of filter or both levels of filters should be tested, and whether the testing should be performed before or after sterilization of the filter. After sterilization testing, consideration should be given to ensuring sterility between the two-stage filters.
Online integrity testing or offline integrity testing can be determined based on process requirements and actual conditions. However, it should be noted that integrity testing is to check the integrity of the entire filtering system, not just the filter itself. Online testing can better ensure the integrity of upstream and downstream connections. When the online testing conditions cannot be met, offline integrity testing can be chosen. At this point, the filter should be kept in the sleeve and disassembled as a whole for direct testing. The filter element should not be disassembled from the stainless steel sleeve for separate testing.
Considering the objectivity of integrity testing results and the reliability of data, automated integrity testers should be used as much as possible at critical usage points. The automated integrity tester should undergo installation confirmation, operation confirmation, and performance confirmation before use. An operating procedure for the use, cleaning, and maintenance of the equipment should be established, as well as a regular preventive maintenance plan (which should include periodic calibration requirements for the equipment).
For the integrity testing of sterilization filters wetted with standard media (water or certain alcohols), the parameter settings should be based on the parameters provided by the filter manufacturer, and the parameters must be verified by the filter manufacturer to prove their correlation with bacterial retention results. Usually, this parameter can be obtained on the quality certificate of the filter.
If non-standard media (usually actual products) need to be used for wetting and integrity testing of sterilization filters in actual processes, the integrity testing limits, such as product bubble point or product diffusion flow standards, must be obtained through validation using actual products as wetting media.
A standard operating procedure for integrity testing should be established, including testing methods, setting of testing parameters, properties and temperature of wetting liquids, wetting operation procedures (such as pressure, time, and flow rate range), testing gases, data recording requirements, etc.
The determination of integrity test results should not be directly based on "pass/fail". The specific numerical values of the test results or the process data in the automatic integrity tester report should be fully recorded and reviewed.
If the integrity test fails, it should be recorded and investigated. Possible influencing factors include insufficient wetting, product residue, incorrect filter installation, system leakage, incorrect filters, incorrect automation program settings, and testing equipment issues. When retesting, the following measures should be taken based on the analysis results, such as strengthening wetting conditions, strengthening cleaning conditions, wetting with low surface tension liquids such as alcohols, testing system airtightness, checking whether the filter model is correct, checking automation program settings, and inspecting equipment. The process and results of retesting should be fully documented.