Mirjam Crul1, Anthe Zandvliet2, Jan Reindert Moes3, Tjitske Veenbaas4, Oscar Smeets5. 1. 1Department of Clinical Pharmacology and Pharmacy, Amsterdam University Medical Center, Amsterdam, the Netherlands. 2. 2Department of Clinical Pharmacy, OLVG, Amsterdam, the Netherlands. 3. 3Department of Clinical Pharmacy, Martini Hospital, Groningen, the Netherlands. 4. 4Department of Clinical Pharmacy, Albert Schweitzer Hospital, Dordrecht, the Netherlands. 5. 5Laboratorium der Nederlandse Apotheken (LNA), Royal Dutch Pharmacy Association (KNMP), the Hague, the Netherlands.
Abstract
Purpose: Bevacizumab (Avastin) is a humanized monoclonal antibody approved by the European Medicines Agency for the intravenous treatment of cancer. However, it is often used as an intravitreal injection for the treatment of macular degeneration or edema. For this purpose, bevacizumab is repackaged from glass vials into plastic syringes. The formation of particles during this compounding process as well as during storage is a source of concern. The aim of this study was to test the sub-visible particulate contamination in bevacizumab material, both in the glass vial and after repackaging into polycarbonate BD Luer-Lok™ syringes. Methods: Syringes with repackaged bevacizumab from 3 different compounding hospital pharmacies were tested for sub-visible particles at different time points during storage at 2-8°C. Results: The batches of bevacizumab starting product complied with the European Pharmacopoeia (Ph. Eur.) for small-volume parenterals. Repackaging into syringes led to an immediate increase in small particles. The number of particles ≥25 μm increased 1.3-fold, and the number of particles ≥10 μm increased 5-fold, respectively. Storage of up to 37 days did not lead to an additional increase in particle counts. All batches complied with the national criteria for particles in intravitreal solutions. Conclusions: Particle count increased due to the repackaging process, but no substantial increase was observed during storage. Formation of sub-visible particles does not impact the shelf-life of bevacizumab repackaged into BD Luer-Lok syringes.
Purpose: Bevacizumab (Avastin) is a humanized monoclonal antibody approved by the European Medicines Agency for the intravenous treatment of cancer. However, it is often used as an intravitreal injection for the treatment of macular degeneration or edema. For this purpose, bevacizumab is repackaged from glass vials into plastic syringes. The formation of particles during this compounding process as well as during storage is a source of concern. The aim of this study was to test the sub-visible particulate contamination in bevacizumab material, both in the glass vial and after repackaging into polycarbonate BD Luer-Lok™ syringes. Methods: Syringes with repackaged bevacizumab from 3 different compounding hospital pharmacies were tested for sub-visible particles at different time points during storage at 2-8°C. Results: The batches of bevacizumab starting product complied with the European Pharmacopoeia (Ph. Eur.) for small-volume parenterals. Repackaging into syringes led to an immediate increase in small particles. The number of particles ≥25 μm increased 1.3-fold, and the number of particles ≥10 μm increased 5-fold, respectively. Storage of up to 37 days did not lead to an additional increase in particle counts. All batches complied with the national criteria for particles in intravitreal solutions. Conclusions: Particle count increased due to the repackaging process, but no substantial increase was observed during storage. Formation of sub-visible particles does not impact the shelf-life of bevacizumab repackaged into BD Luer-Lok syringes.