A filter integrity test is a critical unit operation commonly employed in the bioprocessing industry designed to achieve the following:
- CONFIRM structural integrity of a sterilizing filter
- ENSURE sterilizing filter is properly installed
- COMPLY with all regulatory requirements
There are three primary nondestructive integrity test methods that can be used both before and after filtration:
- Forward flow (diffusion) test
- Bubble point test
- Pressure hold test
Filter integrity testing can be conducted manually or via an automated integrity test machine. The following eight tips will help reduce false failures and improve robustness and reliability:
TIP #1: Consult Filter Vendor
Product specifications and integrity test methods vary by filter. Seek guidance of vendor to clarify methods and ensure proper execution of testing.
TIP #2: Select the Proper Integrity Test Method I: Hydrophilic vs. Hydrophobic
There are two types of sterilizing membrane filters based upon chemical properties: hydrophilic and hydrophobic. For hydrophobic sterilizing membrane filters, a water intrusion test (a secondary, nondestructive integrity test method) is recommended if the primary, nondestructive integrity test methods prove problematic.
TIP #3: Select the Proper Integrity Test Method II: Membrane Structure, Filter Area, & Pore Size
- Bubble Point Test: best suited for testing symmetric membrane filters and small filter installations (e.g., 47 mm disc or single capsule).
- Forward Flow Test (Figure 1): best suited for testing asymmetric membrane filters and large filter installations (e.g., multiple cartridges or capsules).
Note that integrity test methods are only valid if they can be correlated with bacterial removal efficiency. Thus, forward flow, bubble point and pressure hold integrity test methods are suitable for sterilizing membrane filters with pore sizes ranging from 0.10–0.45 micron.
TIP #4: Select the Proper Integrity Test Method III: Manual vs. Automated Integrity Test
Manual Integrity Test:
- Pro: easy to setup and execute.
- Con: test tubing/apparatus connected to the downstream side of the filter (risk of contamination significant).
Automated Integrity Test:
- Pros: instrument connected to upstream side of filter (risk of contamination low); hard record of data (via computer or printout); elimination of operator subjectivity.
Based on pros/cons of both test methods, the automated integrity test is preferred whenever possible.
TIP #5: Maintain Temperature Control (Automated Integrity Test Method)
When using the automated integrity test method, ensure the temperature remains at ambient throughout the entire process. Any fluctuation in test temperature can trigger significant change in pressure and/or volume, resulting in a false failure.
TIP #6: Eliminate Sources of Surface Tension
Thoroughly rinse/flush the empty test housing and all related components (e.g., o-rings). It is imperative that all components utilized are free of surface tension suppression agents (e.g., oil from a new o-ring), as their presence can generate false failures.
TIP #7: Ensure the Test Housing is Properly Sealed & Vented
When installing a filter in the test housing, take great care to ensure filter o-rings don’t become dislodged from respective grooves. Similarly, ensure the housing sump is seated properly on the base o-ring. Proper venting is achieved when a steady stream of liquid (i.e., no air) emits from the vent.
TIP #8: Adhere to a Robust Membrane Wetting Protocol
Finally, the most common mistake that causes false integrity test failures is an inadequately saturated (“wet”) filter. 3M Purification recommends one of the following methods to ensure a completely wet filter prior to conducting an integrity test:
- Soak: stationary exposure of the filter to be tested in the appropriate wetting solution for a minimum of 10 minutes.
- Flush: dynamic exposure of the filter to be tested in the appropriate wetting solution for approximately 5 minutes @ 3 GPM (11.4 LPM) per 10” filter.