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Abstract
Purpose
The aim of this study was to evaluate the stability and sterility of bevacizumab (Avastin, Genentech, Inc., San Francisco, CA, USA) after withdrawal into multiple doses from single-use vials.
Methods
Bevacizumab was repeatedly and aseptically drawn from new vials into 1 cc plastic syringes and refrigerated in the dark at 4°C for 0, 3, 6, 12, 28, 38, 46, 52, or 63 weeks or at, −10°C for 0, 3, 6, 12, 38, 46, or 52 weeks. The stability of bevacizumab was assessed by enzyme-linked immunosorbent assay (ELISA) and compared with that of controls (0 weeks). The contents of the fractionated bevacizumab syringes were analyzed for microbial growth.
Results
When we assessed the relative stability of the bevacizumab stored at 4°C, there was no concentration change for up to 12 weeks. However, concentration decreased by less than 2% between 28 weeks and 46 weeks. Samples stored at −10°C were stable up to 52 weeks. All of the fractionated syringes maintained >90% stability compared with controls for up to one year in both the refrigerated group and the frozen group. The microbial study showed no significant positive results for up to 12 weeks. After intravitreal bevacizumab injection, the statuses of all patients improved, with no signs of intraocular infection. We observed no cases of intraocular infection or complications among the patients.
References
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Figure 1.
(A) The fractionated bevacizumab syringes were sealed with sterile safety caps. (B) For protection from light, the stored bevacizumab syringes were placed in brown plastic bags.
Table 1.
Mean bevacizumab concentration (optical density, OD), decreasing rate bevacizumab concentration for each sample
| Length of storage (weeks) |
Mean bevacizumab concentration (OD, mg/mL) |
Decreasing rate of bevacizumab concentration (OD) (%) |
||
|---|---|---|---|---|
| Stored at 4°C | Stored at −10°C | Stored at 4°C | Stored at −10°C | |
| 0 | 23.5 | 23.5 | 0.0 | 0.0 |
| 3 | 26.4 | 24.6 | 0.0 | 0.0 |
| 6 | 25.3 | 28.1 | 0.0 | 0.0 |
| 12 | 28.9 | 25.6 | 0.0 | 0.0 |
| 28 | 23.1 | * | 1.7 | * |
| 38 | 23.2 | 24.3 | 1.3 | 0.0 |
| 46 | 23.1 | 24.9 | 1.7 | 0.0 |
| 52 | 22.7 | 23.7 | 3.4 | 0.0 |
| 63 | 22.1 | * | 5.6 | * |
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