(M1530-06-37) Effective Methods for Ensuring Dose Accuracy in Low Volume Drug Transfers Using Closed System Transfer Devices

Purpose: In healthcare environments, Closed System Transfer Devices (CSTDs) have been introduced as alternatives to traditional syringes and needles for preparing and administering hazardous drug doses. Concerns have been raised about potential dosing errors when using CSTDs, primarily due to the hold-up volume of these devices¹. This study aims to understand and improve the accuracy of dose preparation when using CSTDs to transfer drug products from vials to IV bags at transfer volumes of ≤ 2 mL^{2, 3}.

Methods: Seven commonly used CSTDs were utilized to transfer drug products from vials to IV bags. Four different methods focused on assessing dose preparation accuracy were evaluated: direct transfer from vial to IV bag without bag spike flushing (method 1), bag spike flushing with the original syringe (method 2), bag spike flushing with a new syringe (method 3), and utilizing a circle priming (method 4).

Results: The control study using syringes and needles for dose preparation with transfer volumes of ≥ 0.1 mL consistently achieved dose accuracy. However, when transferring 0.3 mL using CSTDs, method 1 resulted in under-dosing in 6 out of 7 CSTDs. This suggests that without bag spike flushing, some liquid is retained in the bag spike and does not mix with the diluent in the IV bag. At a transfer volume of ≤ 2 mL using method 2, all CSTDs demonstrated some level of under-dosing or over-dosing, with each device showing variability at different volumes. When transferring volumes ≤ 2 mL using CSTDs with method 3, all doses prepared met the acceptance criteria even at volumes as low as 0.1 mL. The use of a new syringe to flush the bag spike effectively prevented any occurrences of under-dosing or over-dosing. For transfer volumes of as low as 0.1 mL using CSTDs with method 4 resulted in every prepared dose meeting the acceptance criteria. The circle priming effectively eliminated any occurrences of inaccurate dose preparation.

Conclusion: The study demonstrated two effective methods for improving dose accuracy when transferring drug products from vials to IV bags at volumes of 0.1 mL and above using CSTDs. Using a new syringe to flush the bag spike after adding the drug product significantly enhances dose accuracy. Circle priming with an infusion set also substantially improves dose accuracy for low volume transfers. Provided that compatibility with the specific drug product is established, either method is sufficient to ensure accurate dose preparation for low volume transfer.

References: 1. Patke, S.; Gaillat, E. N.; Calero-Rubio, C.; Gooding, T. B.; Audat, H.; Leman, M.; Filipe, V.; Saluja, A., A systematic approach to evaluating closed system drug-transfer devices during drug product development. Journal of Pharmaceutical Sciences 2022, 111 (5), 1325-1334.
2. Lehermayr, C.; Schmelzer, B.; Kropf, M., Closed system transfer devices (CSTDs): Understanding potential over-and under-dosing of liquid vial drug products and how to generally mitigate. Journal of pharmaceutical sciences 2023, 112 (9), 2532-2537.
3. Kulju, S.; McIntosh, B. A.; Fuller, H. J.; Arnold, T.; Gunnar, W., Assessment of unintended volume loss of six closed system transfer devices. Journal of Oncology Pharmacy Practice 2020, 26 (5), 1134-1140.

Acknowledgements: The authors wish to express their gratitude to Michael Meleties for supplying the drug product used in the dose accuracy study and to Tse-Hong Chen for his review of the analytical data.