Michael Wang, Ph.D. 3M Purification

These tips can help you reduce false failures and improve robustness and reliability.

A filter integrity test is a critical unit operation commonly employed in the bioprocessing industry designed to achieve the following:

There are three primary nondestructive integrity test methods that can be used both before and after filtration:

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:

Filter integrity testing can be conducted manually or via an automated integrity test machine, such as 3M’s Minicheck.

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.

Figure 1. Forward flow integrity test (manual method)

TIP #3: Select the Proper Integrity Test Method II: Membrane Structure, Filter Area, & Pore Size

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

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:

Michael Wang, Ph.D., is Senior SASS Specialist II, Scientific Applications Support Services at 3M Purification.

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