Integrity testing filters post-use is a regulatory requirement for products labeled sterile. The bubble point (BP) test is an industry-accepted nondestructive method for testing sterilizing-grade filters for integrity. The BP test is defined as the minimum test pressure at which the liquid within the pore structure of a wetted membrane is forcibly removed from the largest pores by overcoming the capillary forces of those pores. Therefore, the BP depends on the effective diameter of the largest pores. If the observed or measured BP is higher than the validated minimum BP value, then the membrane is within its specification (integral) and sterility of the filtrate is guaranteed.
Small venting hydrophobic filters—like the Midisart® 2000—are utilized on single-use bags, bioreactors, fermenters, and carboys. To ensure the contents of the container remains sterile, a post-use bubble point integrity test is performed on the vent filter. Since the membrane (PTFE) is highly hydrophobic, and not wettable using water only, a low surface tension mixture of isopropanol alcohol (IPA) and water (at a 60/40 ratio) is used as the wetting medium. These small vent filters require ~20 mL of the IPA/water mixture to completely wet the membrane prior to bubble point testing.
Most filters that are post-use integrity tested use an automated instrument (e.g., Sartocheck 4 Plus) to perform BP testing, thereby eliminating the subjectivity associated with human interpretation from the test results. Each automated instrument filter test can take approximately 10–15 minutes to execute. For pharmaceutical sites with large quantities of small area filters, integrity testing can pose a processing bottleneck.
Sartorius Stedim Biotech’s Midisart Test Manifold 10X (Figure 1) enhances productivity by allowing small filter surface area devices to be securely connected in parallel up to 10 ports. It can be wall mounted or placed on a cart.
The use of a filter integrity test manifold that can test up to 10 filters simultaneously, significantly reduces the amount of operator time by ~85% in comparison to individually testing each filter without compromising the accuracy of the test.
To prove the accuracy of using this testing method, individual (0.45 μm and 0.2 μm) filters were each manually wetted with the IPA/water mixture using a syringe and bubble point tested using the integrity test instrument.