Abstract
Purpose: :
Bevacizumab (Avastin, Roche) is a humanised monoclonal antibody licensed for the treatment of metastatic colorectal and breast cancer. Bevacizumab is used ‘off-label’, often repackaged into syringes, for intravitreal administration to treat eye disease. Certain reported adverse events associated with intravitreal administration may be related to deteriorations to the quality of the drug consequent to its repackaging into syringes. This study investigated the purity and stability of repackaged bevacizumab intended for intravitreal administration. It did not seek to investigate any possible bacterial contamination in the samples.
Methods: :
Batches (n=5) of bevacizumab repackaged in syringes (S1 - S5) were obtained from 5 UK outlets with Specials manufacturing licenses. The purity and stability of the samples (stored at 4°C) were tested twice (14 days apart) using an enzyme-linked immunoassay, protein assay by spectrophotometry, polyacrylamide gel electrophoresis (SDS-PAGE) and size exclusion high performance liquid chromatography (SE-HPLC). Particle density and size distribution was assessed by the microflow imaging technique. Data are presented as mean±sd. A p value of <0.05 was considered as being statistically significant.
Results: :
On day one the protein and IgG contents were similar between all the syringes and the control (original packaged bevacizumab from the manufacturer). There were no significant changes in the measurements by day 14. Particle density (particles/ml) was similar between day 1 (11118±1112) and day 14 (11482±1701) in the control samples. However, there was a significant increase in particle density (particles/ml) over the 14 day period for the repackaged bevacizumab (S1: 14102±573 to 40879±6365; S2: 13235±1911 to 34460±3580; S3: 156618±11181 to 420235±22289; S4: 13111±2259 to 21527±1393 and S5: 14071±1194 to 71737±5781, p<0.03 for all comparisons). SDS-PAGE and SE-HPLC profiles were similar between the control and the repackaged samples between the two tests.
Conclusions: :
The increase in particulate matter over time in the repackaged bevacizumab may affect the drug’s safety profile when used for intravitreal injection. It could also be a contributing factor in some reported clusters of intraocular inflammation associated with use of intravitreal bevacizumab in subjects with age-related macular degeneration.
Keywords: age-related macular degeneration • vascular endothelial growth factor