Abstract
Aim
To compare the quality and stability of unlicensed, repackaged bevacizumab intended for intravitreal injection, as provided by five licensed compounding pharmacies in the United Kingdom, with bevacizumab in its original glass vial.
Methods
Repackaged bevacizumab was obtained from five UK suppliers. Samples were analyzed at two time points (day 1 and day 14). Microflow imaging was performed to evaluate subvisible particle size, particle density, and particle size distribution. Protein concentration, immunoglobulin G (IgG) content, and molecular weight were also determined.
Results
A significant difference in subvisible particle density was observed between bevacizumab batches from the five suppliers on day 1 (P<0.001). An increase in subvisible particle density was observed between day 1 and 14 for repackaged bevacizumab from all suppliers (all P<0.05), but not the reference compound. Protein concentration, IgG content, and molecular weight were comparable between batches from each supplier and the reference bevacizumab.
Discussion
The study results indicate that the quality of bevacizumab repackaged into prefilled plastic syringes is variable among the different compounding pharmacies in the United Kingdom. Furthermore, particle density may increase with storage in repackaged syringes. It is noteworthy that particle size distribution in both the repackaged and reference bevacizumab fell outside of the range specified by the United States Pharmacopeia for injectable ophthalmic solutions. These data highlight the need for further research into the use of unlicensed, repackaged bevacizumab intended for intravitreal injection.
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Acknowledgements
This study was supported by Novartis Pharmaceuticals UK Limited. Medical writing support was provided by Fishawack Communications Ltd., Oxford, United Kingdom, and funded by Novartis.
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JMP and FK received a grant from Novartis for this research. WMA has received travel grants from Novartis and Allergan, has participated in clinical trials sponsored by Novartis and Pfizer and has participated in advisory boards for, and received honoraria from, Bayer, Novartis, Allergan and Thrombogenics. WMA’s institution (University of Nottingham) has received research grants from Allergan and Novartis.
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Palmer, J., Amoaku, W. & Kamali, F. Quality of bevacizumab compounded for intravitreal administration. Eye 27, 1090–1097 (2013). https://doi.org/10.1038/eye.2013.139
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DOI: https://doi.org/10.1038/eye.2013.139
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