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CONTAMINATION OF ANTI-VEGF DRUGS FOR INTRAVITREAL INJECTION: How Do Repackaging and Newly Developed Syringes Affect the Amount of Silicone Oil Droplets and Protein Aggregates?

Schargus, Marc, MD*,†; Werner, Benjamin P., MSc; Geerling, Gerd, MD*; Winter, Gerhard, PhD

doi: 10.1097/IAE.0000000000001809
Original Study: PDF Only

Purpose: The particle counts and the nature of particles of three different antivascular endothelial growth factor agents (VEGF) in different containers in a laboratory setting were compared.

Methods: Original prefilled ranibizumab glass syringes, original vials with aflibercept, and repacked ready-to-use plastic syringes with bevacizumab from a compounding pharmacy and a compounding company (CC) were analyzed. Particle counts and size distributions were quantified by different particle characterization methods (nephelometry, light obscuration, Micro-Flow Imaging, nanotracking analysis, resonant mass measurement). Using high-performance size-exclusion chromatography (HP-SEC), levels of protein drug monomer and soluble aggregates were determined.

Results: Nearly all samples showed similar product quality. Light obscuration and Micro-Flow Imaging showed a 4-fold to 9-fold higher total particle count in compounding company bevacizumab (other samples up to 42,000 particles/mL). Nanotracking analysis revealed highest values for compounding company bevacizumab (6,375 million particles/mL). All containers showed similar amounts of silicone oil microdroplets. Ranibizumab showed lowest particle count of all tested agents with only one monomer peak in HP-SEC. Repackaged bevacizumab from different suppliers showed varying product quality.

Conclusion: All three tested agents are available in similar quality regarding particulate purity and silicone oil microdroplet count. Repackaging can have a major impact on the quality.

Intraocular pressure may be elevated after multiple intravitreal antivascular endothelial growth factor injections. One possible mechanism might be the obstruction of trabecular meshwork by protein aggregate accumulation and silicone oil microdroplets. Detailed laboratory analysis revealed a high-quality level for three out of four tested products in different containers. It was shown that all three agents are available in similar qualities regarding particulate purity, but relevant variations exist in particular when repackaging is applied.

*Department of Ophthalmology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany;

Eye Hospital Schweinfurt-Gerolzhofen, Gerolzhofen, Germany; and

Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University, Munich, Germany.

Reprint requests: Marc Schargus, MD, MHBA, FEBO, Department of Ophthalmology, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany; e-mail: marc.schargus@gmx.de

None of the authors has any financial/conflicting interests to disclose.

Owing to the limited number of samples and the need to dilute 20 fold for analysis, the statistical value of the data is limited.

M. Schargus and B.P. Werner contributed equally to this work.

© 2018 by Ophthalmic Communications Society, Inc.