Chemical-gas Sterilization of External Surface of Polymer-based Prefilled Syringes and Its Effect on Stability of Model Therapeutic Protein

Abstract

To reduce the risk of infection during intravitreal injections, the external surface of prefilled syringes (PFSs) must be sterilized. Usually, ethylene oxide (EO) gas or vaporized hydrogen peroxide (VHP) is used for sterilization. More recently, nitrogen dioxide (NO₂) gas sterilization has been developed. It is known that gas permeability is approximately zero into glass-PFSs. However, polymer-PFSs (P-PFSs) have relatively high gas permeability. Therefore, there are concerns about the potential impact of external surface sterilization on drug solutions in P-PFSs. In this study, P-PFSs [filled with water for injection (WFI) or human serum albumin (HSA) solution] were externally sterilized using EO, VHP, and NO₂ gases. For the WFI-filled syringes, the concentration of each gas that ingressed into the WFI was measured. For the HSA solution-filled syringes, the physical and chemical degradation of HSA molecules by each sterilant gas was quantified. For the EO- or VHP-sterilized syringes, the ingressed EO or hydrogen peroxide (H₂O₂) molecules were detected in the filled WFI. Additionally, EO-adducted or oxidized HSA molecules were observed in the HSA-filled syringes. In contrast, the NO₂-sterilized WFI-filled syringes exhibited essentially immeasurable ingressed NO₂, and protein degradation was not detected in HSA-filled syringes.

Keywords: Biopharmaceutical characterization; Chemical stability; Degradation product(s); Diffusion; Oxidation(s); Permeability; Physical stability; Polymer(s); Protein aggregation; Stability.