Assessment of the Microbiological Quality of a Preservative-Free Multidose System following a Mixed Culture Microbial Immersion Challenge

Abstract

Current guidance on the microbiological qualification testing of preservative-free multidose ophthalmic systems is limited and lacking in detail with respect to methodology. This study describes the testing performed to assess the potential for biofilm formation on the tip of a preservative-free multidose device and the microbiological quality of the delivered dose following a mixed culture microbial immersion challenge, simulating a severe, repeated microbial exposure event. Biofilm was assayed quantitatively through viable microbial recovery, semi-quantitatively by staining the biomass in conjunction with ImageJ analysis, and qualitatively by microscopy. The study demonstrated the utility of the immersion challenge as a relevant means of modeling biofilm growth on the preservative-free multidose device nozzle as well as the capability to reliably assess biofilm through a variety of measurements. The study further demonstrated the efficacy of the liner cap as a means of maintaining the microbiological quality of the delivered dose and significantly mitigating biofilm formation following a series of severe microbial immersion challenges.