Evaluation of long-term prevention of microbiological contamination of sterile preparations in a controlled ISO class 5 environment and an uncontrolled environment using a closed-system drug transfer device

Abstract We examined whether a closed-system transfer device (CSTD) can maintain the microbiological integrity of nonpreserved single-use drug vials for an extended period beyond the approved indication for use of 7 days and 10 activations (connection–disconnection cycles) and throughout multiple withdrawals. The CSTD's ability to maintain sterility was examined in a controlled International Organization for Standardization (ISO) class 5 (European Union Good Manufacturing Practice class A) environment and a monitored but uncontrolled environment. In each environmental condition, CSTD vial adaptor units of 20-mm neck size were mounted on three hundred fifty 100-mL glass vials, each containing 100 mL of sterile tryptic soy broth growth medium. Several aliquots (5 mL) from each vial were withdrawn on days 0, 14, and 28. All syringes and the vials containing the remaining growth medium (50 mL) were incubated for 7 additional days between 20 and 25 °C, followed by 7 days between 30 and 35 °C. Incubated samples were inspected for microbial growth daily. No signs of microbial growth were observed in any of the 7,000 samples withdrawn (3,500 in each environment) during the 28-day test period or in the residual growth medium remaining in the vial after all transfers were performed. The study's findings indicate that the tested CSTD safeguards the microbiological sterility of drug preparations for up to 4 weeks after the first puncture. Once a 28-day usage period is approved by regulatory authorities, it may help avoid wasting expensive drugs.