Conference Dates

March 20 – 23, 2022


As single-use systems (SUS) are increasingly expanding into all process steps of commercial manufacturing, integrity failure can significantly impact drug safety, availability, and costs. Consequently, growing industry scrutiny of single-use system integrity (SUSI) is raising the need to develop good science behind reliable determination of liquid leakage and microbial ingress, as well as the appropriate physical integrity testing technologies. In the current study, the results of the experiments performed at Sartorius to understand the mechanisms of liquid leakage and microbial ingress as the foundation for SUSI are presented. This study establishes that there is a relation between liquid leakage and microbial ingress mechanisms in single- use plastic containers. Microbial ingress testing by the aerosolization method and the liquid leakage method are both used to determine the maximum allowable leakage limit (MALL) below which product leakage and bacteria ingress cannot occur in SUS, regardless of the various fluid and process conditions.

To define the MALL, it is generally assumed that a system or a product will not show any microbial ingress or leakage under a certain defect size. However, this study revealed that statistical analysis of the experimental data indicated the probability of MALL encountered at a certain defect size for each system. Finally, a mathematical model was generated to predict the MALL for any use-case of a SUS.

As most physical integrity testing technologies are based on measuring a gas flow rate, additional experiments were performed to find a correlation between a certain defect size and the corresponding gas flow rate. Therefore, the MALL defined at a gas flow rate can be directly linked to established physical integrity testing systems.

As a result, the methods studied provide a more accurate way of predicting ingress, increasing safety down the line for drug manufacturers and patients alike.

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