RT Journal Article
SR Electronic
T1 Single-Use Container Closure Integrity I: Using Microbial Ingress Test Method to Determine the Maximum Allowable Leakage Limit (MALL)
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP pdajpst.2018.009688
DO 10.5731/pdajpst.2018.009688
A1 Aliaskarisohi, Saeedeh
A1 Hogreve, Marc
A1 Langlois, Carole
A1 Barbaroux, Magali
A1 Cappia, Jean-Marc
A1 Menier, Marie-Christine
YR 2019
UL http://journal.pda.org/content/early/2019/04/19/pdajpst.2018.009688.abstract
AB An aerosol microbial ingress test was specifically designed and used to create a predictive model in order to determine the maximum allowable leakage limit (MALL) of single-use systems (SUS). The MALL is defined as the greatest leak size that does not pose any risk on the product. The procedure involved taking test samples of film material of the single-use bags. As test samples, an EVA multilayer film (300 μm thick) and a PE multilayer film (400 μm thick) was cut into 50 mm patches. Artificial defects of 1 µm to 100 µm were laser-drilled in the middle of each film patch. The patch was assembled on a holder and sealed properly. The test units were filled aseptically with culture media and placed inside an aerosol chamber. Certain pressures were applied to the test unit to simulate the constraints that single-use systems may overcome under real-life conditions. After an aerosolization cycle with spores of Bacillus atrophaeus, a minimum concentration of 106 CFU/cm2 was formed on the film surface. The test units were incubated for 14 days at 30°C–35°C and visually inspected for bacterial ingress. Thirty samples per defect size were tested. Logistic regression was used to indicate the maximum allowable leakage limit (MALL) for a single-use system according to the required risk level. With this method, the probability of the occurrence or absence of ingress for a specific defect size was reported according to the experimental data. Besides physical parameters, such as pressure applied and film material, the effect of the probabilistic nature of the microorganisms in determining the MALL is considered.