A worst-case assessment of injectable sterile preparation containers integrity in dynamic conditions to support microbiologic shelf-life extension

Introduction
In our sterile preparation unit, the shelf-life for most of our preparations is set at eight days, whereas literature suggest that physico-chemical stability could be higher, up to one month. To support a potential extension of their shelf life, we first aimed to qualify the microbiological stability of our preparations by assessing integrity of sterile containers in dynamic conditions. This work aims to mimic worst-case conditions during the life cycle of our preparations.

Material and Methods
Two tests were performed based on the GERPAC consensus conference on the Assignment of Microbiological Shelf-life [1] and NHS guidelines [2].
First, containers were filled with sodium chloride 0.9% and immersed in a methylene blue bath for a dynamic intrusion assay. Seven different syringes volumes (n=35) and 50 mL infusion bags (n=10) were agitated for two hours using a Fischer Bioblock Scientific Rotatest Pingpong for 2h at 100 rpm. Containers were incubated for fourteen days at 35°C. The test was validated based on the absence of dye penetration during incubation storage.
Secondly, identical syringes and infusion bags references were filled with tryptic soy broth (TSB) solution and immersed in TSB bath inoculated with an E. coli (Culti-Loops™, Thermo Fisher) at a concentration higher than 106 CFU/mL, determined by bacterial counting. Same dynamic conditions and storage incubation time were applied as previously. Validity relied on the absence of bacterial growth in all containers except positive controls. All results were compared to positive and negative controls.

Results/Discussion
No dye penetration or microbial growth was observed in either test, confirming the physical and microbiological integrity of sterile containers. These findings confirm that our containers are hermetic and prevent bacterial growth, ensuring preparation sterility beyond fourteen days. These results are part of a global assessment of practices within our unit and should be interpreted within a quality framework that includes qualifications of operators, facilities, and equipment.

Conclusion
We believe that dynamic conditions represent a valuable addition to standardized protocols, particularly when considering the lifecycle of a sterile preparation. Indeed, in the context of anticipate and serial production, a standardized preparation may be assigned and returned multiple times, implying a dynamic rather than static lifecycle within a hospital structure.

Keywords : pharmaceutical preparations, microbiology, chemotherapy

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