Stability of Bevacizumab Divided in Multiple Doses for Intravitreal Injection.

OBJECTIVE

To investigate the stability of bevacizumab in multiple doses divided from a single-use vial for intravitreal injection after storage at 4°C for up to six months and under drug transfer condition in tropical climate.

MATERIAL AND METHOD

Five syringes (0.1 mL, 2.5 mg) of bevacizumab were withdrawn each from five new bevacizumab single-use vials (4 mL, 100 mg) under sterile technique. The concentration of bevacizumab in each syringe was measured at two dilutions (2 x 10(6) and 4 x 10(6) fold) using enzyme-linked immunosorbent assay at baseline and after storage at 4°C for 1-, 3-, and 6-month. Each assay was performed at least twice. To simulate the drug transfer condition, bevacizumab was placed in a brown plastic bag and put in another transfer plastic bag with an ice cube for 30 minutes prior to the assay at 1-, 3-, and 6-month.

RESULTS

The concentrations of bevacizumab (mean ± standard deviation) at baseline, 1-, 3-, and 6-month were 26.24 ± 1.95, 25.43 ± 3.80, 27.87 ± 2.81, and 24.25 ± 2.00 mg/mL, respectively. The lowest lower limit of 95% confidence interval for the mean concentration was 23.32 mg/mL at 6-month storage, which was 89% of the mean baseline concentration and considered to be non-inferior to the baseline concentration.

CONCLUSION

Bevacizumab in a single-use vial could be divided into multiple small doses for intravitreal injection with sufficient stability when refrigerated at 4°C for up to six months and under the drug transfer condition in tropical climate.