Evaluation of Aflibercept and Ziv-Aflibercept Binding Affinity to Vascular Endothelial Growth Factor, Stability, and Sterility after Compounding

Abstract

Purpose : To investigate the binding affinity, stability, and sterility of aflibercept and ziv-aflibercept to vascular endothelial growth factor (VEGF) after compounding and storage for up to 28 days at 4°C and -8°C.

Methods : Tuberculin-type 1-mL syringes were prepared containing aflibercept (40 mg/mL) and ziv-aflibercept (25 mg/mL). Aflibercept and ziv-aflibercept samples were stored at 4°C and -8°C for 0, 14, and 28 days and evaluated for the binding affinity of anti-VEGF to VEGF and stability using enzyme-linked immunosorbent assays. The amounts of aflibercept and ziv-aflibercept recovered under different storage conditions and evaluation of sample sterility were determined.

Results : Laboratory trials with aflibercept and ziv-aflibercept showed preservation of the drug-binding capability to recombinant VEGF when stored in plastic syringes for up to 28 days at 4°C and -8°C. The masses expected in the syringes containing aflibercept and ziv-aflibercept were 2.048 mg and 1.280 mg, respectively (table 1); the respective concentrations expected in the syringes were 0.200 µg/mL and 0.250 µg/mL (P<0.05) (table 2). No significant decreases in mass or concentrations were observed for up to 28 days of storage under the different conditions. Microbiologic evaluations did not detect contamination in the syringes after the storage periods at both temperatures.

Conclusions : The current study corroborates the data reported in the literature, i.e., that compounded anti-VEGF drugs aflibercept and ziv-aflibercept do not loose stability or binding affinity and do not become contaminated if prepared under sterile conditions and stored at 4°C or -8°C for 14 or 28 days.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.