Prefilled Syringe Injection Force Impact Assessment from Back Pressure: An Approach for Testing Syringe Injectability In Situ vs. In Vitro

Abstract

Prefilled syringes are commonly used combination products for parenteral drug and vaccine administration. The characterization of these devices are through functionality testing, such as injection and extrusion force performance. This testing is typically completed by measuring these forces in a nonrepresentative environment (i.e. dispensed in-air) or route of administration conditions. Although injection tissue may not always be feasible or accessible for use, questions from the health authorities make it increasingly important to understand the impact of tissue back pressure on device functionality. Particularly for injectables containing larger volumes and higher viscosities which can widely impact injection and user experience. This work evaluates a comprehensive, safe, and cost-effective in situ testing model to characterize extrusion force while accounting for the variable range of opposing forces (i.e. back pressure) experienced by the user during injection into live tissue with a novel test configuration. Due to the variability of back pressure presented by human tissue for both subcutaneous and intramuscular injections, tissue back pressure was simulated (0 psi - 13.1 psi) using a controlled, pressurized injection system. Testing was conducted across different syringe sizes (2.25mL, 1.5mL, 1.0mL) and types (Luer lock, stake needle) with two simulated drug product viscosities product (1cP, 20cP). Extrusion force was measured using a Texture Analyzer mechanical testing instrument with crosshead speeds of 100 mm/min and 200 mm/min. The results demonstrated that there is a contribution of increasing back pressure on extrusion force across all syringe types, viscosities, and injection speeds which can be predicted using the proposed empirical model. Moreover, this work demonstrated that the factors that largely influence the average and maximum extrusion force during injection are syringe and needle geometries, viscosity, and back pressure. This understanding of the device usability may aid in the development of more robust prefilled syringe designs to minimize use-related risks.