Bevacizumab for Intravitreal Injection: Impact of Sub-Visible Particles on the Shelf-Life of Repackaged Bevacizumab

Mirjam Crul, Anthe Zandvliet, Jan Reindert Moes, Tjitske Veenbaas, Oscar Smeets

Research output: Contribution to journalArticleAcademicpeer-review

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.

Cite this

@article{d37bd0f7ea3a44078c901243a9f0069c,
title = "Bevacizumab for Intravitreal Injection: Impact of Sub-Visible Particles on the Shelf-Life of Repackaged Bevacizumab",
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.",
author = "Mirjam Crul and Anthe Zandvliet and Moes, {Jan Reindert} and Tjitske Veenbaas and Oscar Smeets",
year = "2019",
month = "6",
day = "28",
doi = "10.1089/jop.2019.0042",
language = "English",
journal = "Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics",
issn = "1080-7683",

}

TY - JOUR

T1 - Bevacizumab for Intravitreal Injection

T2 - Impact of Sub-Visible Particles on the Shelf-Life of Repackaged Bevacizumab

AU - Crul, Mirjam

AU - Zandvliet, Anthe

AU - Moes, Jan Reindert

AU - Veenbaas, Tjitske

AU - Smeets, Oscar

PY - 2019/6/28

Y1 - 2019/6/28

N2 - 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.

AB - 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.

U2 - 10.1089/jop.2019.0042

DO - 10.1089/jop.2019.0042

M3 - Article

JO - Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics

JF - Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics

SN - 1080-7683

ER -