Radiopharmaceutical Production Filter integrity test STOP
Filter Integrity Test • The filter integrity test is one of the most important tests that are carried out on the final product. • A satisfactory result from this test gives assurance that the final product is sterile and therefore acceptable for human use. Contents • Acceptance Criteria • Discussion • Procedure • Example SOP
Filter integrity test Acceptance Criteria: The membrane filter integrity test is not mentined in the International Pharmacopeia. However, it is a requirement of GMP guidelines on aseptic processing using final sterilizing filtration. It is highly recommended that this test is performed prior to release of the product.
Filter integrity test Discussion: Although this test is not required by the International Pharmacopeia, the fact that the sterility test results will not be available when the radiopharmaceutical is injected, assessment of the filter integrity using bubble point or pressure-retaining test represents an appropriate indication of the performance of the aseptic processing and sterility of the product. Therefore, it is highly recommended that the filter integrity test be performed after dispensing and prior to release of the FDG product batch. It must be emphasized that the filter integrity test does not replace the required sterility test.
Filter integrity test Procedure: Connect to a three way valve a 50-60 cc syringe, a pressure gauge (reading >60 psi), and the filter being tested. (If using a vented filter, block the vent hole with a drop of oil). At end of the filter, attach an extension tube, other end of which is dipped in a beaker filled with water. As pressure is applied by pushing the plunger, record the pressure reading when continuous stream of bubbles is formed in water. Nominal pressure reading for an intact filter is >45 psi.
Example Procedure Vented filter procedure Filter Wetting: The filter must have been thoroughly wetted prior to testing. Using it for final product filtration wets it adequately. The vent should be closed with mineral oil Mounting the Filter: Mount the filter in the Bubble Point testing apparatus. There is a female Luer fitting on top of the bubbling chamber (Picker vial with water in it) and a male Luer fitting on a 1/8" line for the gas supply. Initial Pressure Test: Turn V2 to "Test" and then turn V1 to "Low." This will apply a pressure of 35 psig to the filter. Observe that there is not a stream of bubbles exiting the filter. A single bubble or two is quite acceptable as the gas pressure forces the filter to deform slightly. Find the Bubble Point: Turn V1 to "High" to slowly increase the pressure to the rated bubble point of the filter. Note the pressure at which the filter begins to pass a steady stream of bubbles. Record the bubble point pressure in the batch record. Technically the filter passed the manufacturer specifications when it held ≥32 psig.
Example Procedure Unvented filter Procedure Filter Wetting: Wet the filter with the appropriate fluid, typically water for hydrophilic membranes or an alcohol/water mixture for hydrophobic membranes. Pressurize the system to about 80% of the expected bubble point pressure which is stated in the manufacturer’s literature. Slowly increase the pressure until rapid continuous bubbling is observed at the outlet. A bubble point value lower than the specification is an indication of one of the following: • fluid with different surface tension than the recommended test fluid • integral filter, but wrong pore size • high temperature • incompletely wetted membrane • non-integral membrane or seal Link to Demonstration