Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Vitreoretinal Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Sci Rep. 2022 Feb 22;12(1):2971. doi: 10.1038/s41598-022-06831-2.
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.
评估在受控（4°C）和环境（25.8°C）温度下，将重组 Ziv-aflibercept 在 1 毫升塑料结核菌素注射器中重新包装，用于玻璃体腔内注射的无菌性、稳定性和疗效，最长可储存 90 天。共制备了 168 个结核菌素 1 毫升注射器，其中含有 Ziv-aflibercept（100mg/4mL）。样品在 4°C 和 25.8°C 下储存 0、3、7、14、21、28、60 和 90 天。在每个时间点，使用酶联免疫吸附测定（ELISA）评估 4 个样品的抗 VEGF 与 VEGF 的稳定性和结合亲和力（疗效）。所有样品均进行微生物生长分析。在每个时间点，都没有从任何 Ziv-aflibercept 样品中获得微生物生长，这表明在 4°C 和 25.8°C 下重新包装的 Ziv-aflibercept 保持无菌。ELISA 分析显示浓度没有明显下降，结合亲和力也没有下降，这表明稳定性和疗效得以保持。然而，在 4°C 下储存 60 天后和在 25.8°C 下储存 30 天后，Ziv-aflibercept 的浓度下降到低于 8ng/mL 的最低预期浓度以下。如果在无菌条件下制备并在 4°C 下储存长达 60 天或在 25.8°C 下储存长达 30 天，重新包装的抗 VEGF 药物 Ziv-aflibercept 不会失去稳定性或疗效，也不会受到污染。
