PT - JOURNAL ARTICLE AU - Saeedeh Aliaskarisohi AU - Chethan Kumar AU - Marc Hogreve AU - Nelly Montenay AU - Jonathan Cutting AU - Ashok Mundrigi AU - Anilkumar Paramathma TI - Single-Use System Integrity II: Characterization of Liquid Leakage Mechanisms AID - 10.5731/pdajpst.2020.012088 DP - 2020 Jan 01 TA - PDA Journal of Pharmaceutical Science and Technology PG - pdajpst.2020.012088 4099 - http://journal.pda.org/content/early/2020/11/16/pdajpst.2020.012088.short 4100 - http://journal.pda.org/content/early/2020/11/16/pdajpst.2020.012088.full AB - This study investigated the liquid leakage mechanism through microchannels in a flexible single-use packaging system composed of multilayer plastic film. Based on this study, a relationship between the maximum allowable leakage limit (MALL) and the loss of package integrity can be established under different use-case conditions. The MALL is defined as the greatest leak size that does not pose any risk to the product. A specifically designed liquid leak test was used to determine the leakage time, i.e., the time it takes for a package to show leakage. As a result, this method is able to determine the leak size for which no liquid leakage is observed after 30 days. This leak size varies between 2 μm and 10 μm and can be considered the MALL for liquid egress under different use-case conditions. This paper also compares the MALL results of this liquid leak test with those of the microbial ingress test, with showing a direct correlation between both tests. As test samples, an ethylene vinyl acetate multilayer film (300 μm thick) and a polyethylene multilayer film (400 μm thick) were cut into 50 mm patches. Before the patches were assembled in a filter holder to form a leak-tight seal, artificial leaks in sizes of 2 μm − 25 μm were laser-drilled into the center of each patch. The test units were filled aseptically with culture media and mounted vertically on the test setup. Various pressures were applied to each test unit to simulate the constraints that single-use systems may be subject to under real-world conditions. To detect the exact leakage time, electric circuits with timers were attached below each film patch. Microscopic investigations, including light microscopy and computed tomography, were used to interpret and understand the physics and geometries of the microchannels in order to explain any deviation from the expected results.