Variables Impacting Silicone Oil Migration and Biologics in Prefilled Syringes.

Prefilled syringes (PFS) as a primary container for parenteral drug products offer significant advantages, such as fast delivery time, ease of self-administration and fewer dosing errors. Despite the benefits that PFS can provide to patients, the silicone oil pre-coated on the glass barrels has shown migration into the drug product, which can impact particle formation and syringe functionality. Health authorities have urged product developers to better understand the susceptibility of drug products to particle formation in PFS due to silicone oil. In the market, there are multiple syringe sources provided by various PFS suppliers. Due to current supply chain shortages and procurement preferences for commercial products, the PFS source may change in the middle of development. Additionally, health authorities require establishing source duality. Therefore, it is crucial to understand how different syringe sources and formulation compositions impact the drug product quality. Here, several design of experiments (DOE) are executed that focus on the risk of silicone oil migration induced by syringe sources, surfactants, protein types, stress, etc. We utilized Resonant Mass Measurement (RMM) and Micro Flow Imaging (MFI) to characterize silicone oil and proteinaceous particle distribution in both micron and submicron size ranges, as well as ICP-MS to quantify silicon content. The protein aggregation and PFS functionality were also monitored in the stability study. The results show that silicone oil migration is impacted more by syringe source, siliconization process and surfactant (type & concentration). The break loose force and extrusion force across all syringe sources increase significantly as protein concentration and storage temperature increase. Protein stability is found to be impacted by its molecular properties and is less impacted by the presence of silicone oil, which is the same inference drawn in other literatures. A detailed evaluation described in this paper enables a thorough and optimal selection of primary container closure and de-risks the impact of silicone oil on drug product stability.

The Impact of Syringe Age Prior to Filling on Migration of Subvisible Silicone-Oil Particles into Drug Product.

Silicone oil is often applied to the inner surface of glass syringes and cartridges to reduce friction between the glass surface and elastomeric plunger stopper. This oil can appear as intrinsic and non-proteinaceous particles in the ejected fluid or drug product. Limited data is available to understand the impact of age (time between syringe manufacture and filling) on silicone oil migration into the drug product. This study compares subvisible particle count and extrusion force of siliconized syringes from two different manufacturers stored at ambient condition for 2-3 (fresh syringes) and 13-14 (aged syringes) months then filled and placed at 40°C for an additional three months. The fresh syringes exhibit a 2.5-fold increase in subvisible particle count compared to those aged ones. Moreover, the fresh syringes exhibit up to a 2-fold increase in extrusion force. These findings suggest the degree and amount of silicone oil migration is influenced by the time in storage of the glass syringe prior to filling. This rapid communication highlights syringe storage time prior to filling as a factor to be considered during development.