Investigation of the Sterility of Diluent in Prefilled Syringes Used for Vaccine Reconstitution at Department of Defense Recruit Training Sites

Abstract Introduction Measles, mumps, and rubella (MMR) and varicella (VAR) vaccines are the two vaccines administered in large recruit training sites (RTS) that require a single-use syringe to be prefilled with the diluent (ie water) before vaccine reconstitution. Since there are no preservatives in either MMR or VAR vaccines, it is critical to maintain the diluent sterile to ensure the sterility of the reconstituted vaccine. The Department of Defense/Defense Health Agency has instructions on reconstitution of lyophilized vaccines and guidelines for their storage. Vaccine manufacturers provide instructions on how to properly store the diluent. However, there is no clear guidance or standard operating procedures regarding the best practice for preparation and storage of the syringes prefilled with diluent. Various RTS across all four services have their respective routines to best fit their vaccination requirements. Currently, there are no available data on the sterility status of the diluent prepared using these various routines before they are used to reconstitute vaccines. Materials and Methods We investigated the sterility of the diluent (ie water) in prefilled syringes prepared using routines practiced at various RTS. Diluent was drawn up into single syringes and was kept under various conditions (4 °C or room temperature for overnight up to 24 hours) used by various RTS. At indicated time, diluent was injected into sterile vials and the sterility of the diluent was determined by monitoring the presence/growth of bacteria (including aerobic bacteria, mycoplasma, and an obligate intracellular bacterium, Coxiella burnetii), fungi, and viruses for up to 21 days after inoculation into proper and specific culture media. Both traditional cell culture and molecular assays were used to demonstrate the presence or absence of contamination that may compromise the sterility of the diluent. Results Our results demonstrate that the diluent, after being drawn up to fill the syringe, maintains sterility after storage for overnight up to 24 hours at room temperature or 4 °C with or without recapping the syringes, suggesting that current vaccine reconstitution routines practiced at large military RTS are safe. Conclusions Our results demonstrate that in spite of variations in current practices used in various RTS, the diluent in the prefilled syringe tested from each site maintains its sterility and was determined to be safe for use in military health system-wide vacc