A Case Study to Address a Gap in the Device-to-Vial Interface Stopper Push-in by Chemo Spikes

Abstract

This case study is the first to address the risk, at the device-to-vial interface, of a spike pushing a stopper into a vial. It was performed after healthcare workers at cancer care hospitals complained about the risk of possible exposure to hazardous injectable drugs during the transfer if the spike pushed the stopper into the vial. This case study took a three-step approach to understand the device-to-vial interface, and the factors that determine stopper push-in force threshold and spike puncture force, respectively. The results show that the stopper push-in force threshold varies with the spike size, stopper properties, and stopper design; while the spike puncture force is determined by spike design, spike surface lubricity, stopper properties, and stopper design. The case study suggests that, to mitigate the risk of stopper push-in, the spike puncture force needs to be significantly lower than the stopper push-in force threshold, measured with a flat tip test probe having the same outside diameter as typically used spikes. In addition, although some factors which impact stopper push-in force threshold also impact spike puncture force in the same trend, such as stopper material, other factors which impact stopper push-in force threshold do not impact spike puncture force, and vice versa. For example, the spike length and cross section area contribute to stopper push-in force threshold but do not have significant impact on puncture force. It would be misleading to just compare the absolute values of spike puncture forces but neglect the dimensional factors. From the stopper and spike compatibility perspective, the case study provides a methodology to quantify the risk of stopper being pushed into the vial by the spike, and suggests a process to prevent the stopper push-in from occurring. The study also shows that the human factor is another important element in the stopper push-in issue. It emphasizes the need for a joint effort for risk mitigation across the board among stopper manufacturers, spike manufacturers, pharmaceutical manufacturers, device manufacturers, and hospitals (pharmacies & healthcare workers). Device and drug developers need to properly select and test stoppers and containers with intended spikes. Healthcare workers need to use compatible stoppers and spikes, and need to use them correctly.

An Industry Perspective on the Challenges of Using Closed System Transfer Devices with Biologics and Communication Guidance to Healthcare Professionals

“…The force required to push the spike through the stopper increases as the stopper thickness increases. 16 This investigation highlights the importance of proper site training and technique to reduce the risk to vial wastage. Other challenges in relation to stopper coring and intrusion include leakage, breakage of vials, user fatigue and hand injuries.…”

“…Additionally, West Pharmaceutical Services has conducted a thorough root cause analysis to understand the factors that lead to stopper intrusion, where the stopper is pushed into the vial, including puncture force, spike diameter, puncture location, and stopper thickness. 16 West concluded that the highest risk of stopper intrusion occurs when the spike puncture is misaligned with the center of the stopper. The force required to push the spike through the stopper increases as the stopper thickness increases.…”

“…Hospital and clinical sites typically adopt the use of a single CSTD system from a single manufacturer for use with all products at their site. 16 Several criteria for site evaluation have been proposed. These typically include cost, ease of use, alignment with vendor, leak and wipe testing and quality of training.…”

An Industry Perspective on Compatibility Assessment of Closed System Drug-Transfer Devices for Biologics

“…Other risks associated with CSTD use may include possible lubricants and leachables, 4,5 stopper coring/fragmentation, 6 and stopper push-in. 7 at the device-to-vial interface. Additionally, some CSTDs may contribute to dose inaccuracy, in cases where the device design and/or hold-up volume prevents complete withdrawal of the product from the primary DP container and/or transfer of the dose into the infusion container.…”

Challenges of Using Closed System Transfer Devices With Biological Drug Products: An Industry Perspective

“…Issues with stoppers, especially stoppers being pushed in for vials containing lyophilized formulations, were also noted as a challenge. A recent report by Zhao et al 7 emphasized the need for device and drug developers to properly select and test stoppers and containers with intended spikes to prevent stopper push in from occurring. Petoskey et al 8 recently reported the complexities of CSTDs, especially in terms of lubricants, with an antibody drug conjugate.…”