Development of a Vial-to-Vial Transfer Device for Reconstitution of a Lyophilized Drug Product

Hepatitis D virus (HDV) is a severe form of viral hepatitis, affecting over 12 million people. Hepcludex®, developed by Gilead Sciences, is the first and only approved treatment for HDV. It is a daily treatment that, due to its instability in liquid form, requires mixing a sterile water (sWFI) vial with a powder vial using a transfer needle. Currently, patients must follow a multi-step reconstitution process: first, withdrawing exactly 1.00 ± 0.05 mL of sWFI without air bubbles, then slowly transferring it into the Hepcludex® vial while preventing fluid turbulence. After swirling the vial to complete reconstitution, patients must use another syringe to withdraw the solution for injection. This process is prone to user error, leading to dosing inaccuracies and treatment non adherence. A primary challenge is air bubble formation, which makes the process time-consuming and inaccurate, leading to suboptimal treatment outcomes. Existing transfer devices lack precision, allowing uncontrolled water flow until depletion. To solve these challenges, we developed a mechanical vial-to-vial transfer device that ensures precise fluid transfer while eliminating the need for a transfer needle. Our device features a controlled transfer cavity that relies on gravity-driven fluid movement and volume exchange to accurately withdraw and deposit 1.00 ± 0.05 mL of sWFI. The system includes a two-channel puncture design, which first directs the sWFI from its vial into a cavity, ensuring precise volume measurement before transferring the liquid into the drug vial. The puncture design allows air to move freely between the cavity and the sWFI vial, enabling fluid replacement as liquid enters the cavity. The rotating cavity mechanism then facilitates the transfer of the measured liquid into the drug vial. Experimental testing confirmed the effectiveness of our design, demonstrating consistent fluid transfer. Refinements to the puncture design optimized flow dynamics, reducing water adhesion, preventing droplet formation, and eliminating air entrapment into the transfer cavity and Hepcludex® vial. Volume transfer accuracy tests demonstrated that the device achieved a mean transfer volume of 1.0000 mL, with a 99.95% confidence interval of [0.9792, 1.0208], exceeding the required clinical accuracy threshold. Additional material investigation identified Glass-Filled Polyethylene Terephthalate (PET) with Polyethylene Glycol (PEG) Coating as a promising candidate for injection-molded prototype. Providing a needle-free, highly accurate solution, this device improves at-home treatment accessibility for HDV patients while reducing fluid transfer errors. Future work includes material selection, regulatory approval, and clinical validation for adoption.