MALIK Y. KAHOOK,1 LU LIU,2 PHILIP RUZYCKI,1 NARESH MANDAVA,1 JOHN F. CARPENTER,2 J. MARK PETRASH,1 DAVID A. AMMAR,1
1Department of Ophthalmology, Rocky Mountain Lions Eye Institute, University of Colorado Denver, Aurora, Colorado;
2Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology, University of Colorado Denver, Aurora, Colorado.
PUBLICATION: Retina 30(6): 887-892. (2010)
DOI: 10.1097/IAE.0b013e3181d50cea
ABSTRACT:
Purpose: The antivascular endothelial growth factor agents ranibizumab and bevacizumab are used to treat ocular neovascular diseases. There have been recent reports of sustained elevation of intraocular pressure after use of either agent, which we hypothesize could be because of high–molecular-weight aggregates.
Methods: Enzyme-linked immunosorbent assay, size exclusion chromatography, and polyacrylamide gel electrophoresis were used to analyze repackaged bevacizumab syringes obtained from three outside compounding pharmacies and samples obtained directly from the original vial. Microflow imaging was used to examine particulate material within samples.
Results: All syringes contained statistically similar amounts of protein, consisting of immunoglobulin (IgG) heavy and light chains (polyacrylamide gel electrophoresis). However, two of the three compounding pharmacies’ batches had significantly less functional IgG in the solution (enzyme-linked immunosorbent assay). Additionally, the compounding pharmacies with the lowest IgG (~50%) also contained 10-fold the number of micron-sized particulate matter as measured by microflow imaging.
Conclusion: There are significant differences in IgG concentration measured from repackaged bevacizumab syringes. A trend exists for an increase in micron-sized protein aggregates with the decrease in IgG concentration. Large particulate matter within some samples may lead to obstruction of aqueous outflow and subsequent elevation in intraocular pressure. Additional studies are warranted to explore these findings.
LINK TO ARTICLE: http://journals.lww.com/retinajournal/Abstract/2010/06000/High_Molecular_Weight_Aggregates_in_Repackaged.7.aspx
