LONG-TERM PHYSICAL STABILITY, STERILITY, AND ANTI-VEGF BIOACTIVITY OF REPACKAGED BEVACIZUMAB IN 2-ML GLASS VIALS

Abstract

Purpose: Repackaged bevacizumab in single-dose, prefilled syringes for intravitreal injection is available, but with shelf life limited from 60 days to 90 days. For the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2), 2-mL sterile glass vials were used rather than prefilled syringes to provide a longer shelf life for study supplies.

Methods: Repackaged bevacizumab in glass vials was tested at release and, for 1 lot, after 1, 3, 6, and 12 months for physical stability, including concentration, purity and appearance, and for sterility and endotoxins. Vials from 2 lots were tested at release and after 20 months and 21 months, respectively. One lot was tested at 21 months for anti-VEGF bioactivity compared with a fresh supply of commercial bevacizumab.

Results: Repackaged bevacizumab in 2-mL glass vials continued to meet all quality release specifications and remain sterile for up to 21 months. In addition, no degradation in anti-VEGF bioactivity was observed at 21 months compared with a fresh bevacizumab control.

Conclusion: Bevacizumab can be repackaged into small, single-dose glass vials for intravitreal injection and the qualities of the commercial product maintained, including anti-VEGF bioactivity, for up to 21 months in refrigerated storage. Consideration should be given to repackaging bevacizumab for ophthalmic use in small glass vials as opposed to plastic syringes.

Conflict of interest statement

None of the authors has any proprietary interest in any of the products mentioned in this article.

Figures

Figure 1

GloResponse™ bio-assay results for VEGF-A inhibition for repackaged bevacizumab in vial ID #126691 (upper panel) and vial ID #127013 (lower panel) of Lot #5082003 after storage for 21 months at 4° ± 2°C. Rounded, blue markers are for the fresh reference standard AVASTIN® sample. The assay uses NFAT-RE-luc2P/KDR HEK293 cells that have been transfected with the VEGF receptor (KDR). Responses are in calibrated luminance units (LU) and error bars are ± the standard deviation for at least 6 replicate pair determinations at each dilution. Relative potency estimates were 108.5% (upper panel) and 103.0% (lower panel), compared to the reference standard control. Unrestrained curves were fitted by a 4-parameter regression program, and all r2 correlation coefficients for the fit line are >0.99.

Figure 1

GloResponse™ bio-assay results for VEGF-A inhibition for repackaged bevacizumab in vial ID #126691 (upper panel) and vial ID #127013 (lower panel) of Lot #5082003 after storage for 21 months at 4° ± 2°C. Rounded, blue markers are for the fresh reference standard AVASTIN® sample. The assay uses NFAT-RE-luc2P/KDR HEK293 cells that have been transfected with the VEGF receptor (KDR). Responses are in calibrated luminance units (LU) and error bars are ± the standard deviation for at least 6 replicate pair determinations at each dilution. Relative potency estimates were 108.5% (upper panel) and 103.0% (lower panel), compared to the reference standard control. Unrestrained curves were fitted by a 4-parameter regression program, and all r2 correlation coefficients for the fit line are >0.99.