Prefilled Syringes: Advancements in Drug –Device Combination Systems

Prefilled syringes (PFS) have undergone a paradigm shift, transitioning from passive primary container closure systems into complex, integrated drug-device combination products designed for modern biopharmaceuticals. Their ready-to-administer presentation streamlines clinical workflows, ensures rigorous dosing precision, minimizes contamination risks, and facilitates patient-centric home self-administration. The rapid proliferation of therapeutic monoclonal antibodies, recombinant proteins, peptides, and high concentration subcutaneous formulations has underscored the vital importance of container contact materials, silicone lubrication dynamics, needle geometry, and mechanical device integration. Contemporary PFS platforms encompass traditional Type I borosilicate glass, cyclic olefin polymer (COP), cyclic olefin copolymer (COC), and specialized silicone-reduced or silicone-free platforms. Each material matrix presents a distinct trade-off regarding gas/moisture barrier properties, fracture resistance, dimensional tolerances, extractables (E&L) profiles, and interface-induced drug degradation. For biological macromolecules, drug-container compatibility represents a critical quality attribute (CQA); protein adsorption and interfacial denaturation at glass, polymer, elastomer, air-liquid, and silicone-oil interfaces frequently induce subvisible particle generation and irreversible aggregation. Silicone oil microdroplets remain a focal technical challenge due to potential migration and nucleation effects, while residual manufacturing contaminants such as tungsten species can induce localized protein unfolding. Concurrently, injectability functionality is paramount for viscous high-concentration biologics, were hydraulic resistance and extrusion dynamics scale critically with needle lumen diameter and fluid rheology. This review provides a comprehensive review covering component architecture, material interaction pathways, silicone dynamics, fluid mechanical modelling, clinical human factors, regulatory frameworks, and next-generation smart delivery devices Keywords: Prefilled syringe; Drug-device combination system; Primary container closure; Biologics stability; Monoclonal antibodies; Silicone oil migration; Cyclic olefin polymer (COP); Injectability mechanics; Autoinjectors; Extractables and Leachables (E&L)