The sterility, stability and efficacy of repackaged ziv-aflibercept for intravitreal administration

Abstract

To evaluate the sterility, stability, and efficacy of repackaged ziv-aflibercept in 1-mL plastic tuberculin syringes for intravitreal injection after storage for up to 90 days at controlled (4 °C) and ambient (25.8 °C) temperature. A total of 168 tuberculin-type 1-mL syringes were prepared containing ziv-aflibercept (100 mg/4 mL). Samples were stored at 4 °C and 25.8 °C for 0, 3, 7, 14, 21, 28, 60, and 90 days. At each time point, four samples were evaluated for the stability and binding affinity of anti-VEGF to VEGF (efficacy) using enzyme-linked immunosorbent assays (ELISAs). All samples were analyzed for microbial growth. No microbial growth was obtained from any of the ziv-aflibercept samples during each time point, indicating that the repackaged ziv-aflibercept stored at 4 °C and 25.8 °C remained sterile. ELISA analysis revealed no significant decrease in concentration, and binding affinity was observed, indicating that the stability and efficacy were preserved. However, the concentration of ziv-aflibercept decreased less than the minimum expected concentration of 8 ng/mL after 60 days at 4 °C and after 30 days at 25.8 °C. The repackaged anti-VEGF drug ziv-aflibercept does not lose stability or efficacy and remains uncontaminated if prepared under sterile conditions and stored at 4 °C for up to 60 days or stored at 25.8 °C for up to 30 days.