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Repackaging of anti-VEGF may affect quality profile in intraocular injection use
Changes in particle size and density were detected over the study period in single-dose repackaged bevacizumab.
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Quality assessment of repackaged bevacizumab into plastic syringes for intraocular administration showed lack of stability and inconsistent results between samples, according to a study.
“Bevacizumab is a humanized monoclonal antibody which is licensed for the treatment of metastatic colorectal and breast cancer. It is repackaged into syringes for unlicensed intravitreal administration to treat eye diseases. We cannot exclude that some adverse events reported with bevacizumab might be related to deterioration in the quality of the drug consequent to its repackaging into syringes,” Winfried Amoaku, MD, said at the Euretina meeting in Milan.
The study investigated the quality and stability of repackaged bevacizumab obtained from five different outlets in the U.K. with special manufacturing licenses. Avastin (bevacizumab, Genentech) for intravitreal infusion in the original glass vial was used as reference compound. As for standard clinical use, the repackaged syringes were shipped in hypothermic containers directly from the supplier. Both the syringes and the original compound were stored at 4°C in a laboratory before analysis.
Winfried Amoaku
The quality and stability of the samples were tested at days 1 and 14 using an enzyme-linked immunoassay, protein assay by spectrometrometry, polyacrylamide gel electrophoresis (SDS-PAGE) and size exclusion high-performance liquid chromatography (SE-HPLC). Particle density and size distribution were assessed by the microflow imaging technique (MFI 5000 Series Flow Microscope, Brightwell). Bacterial contamination testing was not within the study purposes.
Results
The study showed no significant results in the control between day 1 and day 14.
“At day 1 the protein and IgG contents were similar between all the syringes and the control. No significant changes occurred by day 14,” Amoaku said.
Results were similar for bevacizumab repacked in syringes obtained from the five suppliers and the reference compound.
“SDS-PAGE results for bevacizumab samples treated with and without dithiothreitol reduction showed no difference between samples. SE-HPLC did not reveal any detectable differences between repackaged bevacizumab and the reference compound,” Amoaku said.
However, changes in particle size and density were detected over the study period in the repackaged compound.
“There were no significant differences in mean particle size at day 1 between batches obtained from the different suppliers, but significant differences between batches were seen at day 14. No changes in particle size were found in the reference compound over this period,” Amoaku said.
Density was also similar between day 1 and day 14 in the control glass vial, while significant differences were found at day 1 between batches. A significant increase in density was seen in all syringes between day 1 and day 14.
“The increase in particle density over time may affect the drug’s safety profile when used for intravitreal injection,” Amoaku said. “It may also be a contributing factor in some reported clusters of intraocular inflammation associated with intravitreal bevacizumab administered in subjects with age-related macular degeneration.”
Safety issues related to these findings should be further investigated, he said. – by Michela Cimberle
- For more information:
- Winfried Amoaku, MD, can be reached at University Hospital, Queen’s Medical Centre, Nottingham, U.K.; email: Winfried.Amoaku@nottingham.ac.uk.
Disclosure: This research was sponsored by Novartis. Amoaku has received educational travel grants from Allergan, Bayer and Novartis. He has also undertaken research sponsored by Novartis and Pfizer and served on advisory boards for Bayer, ThromboGenics, Novartis and Pfizer.