Department of Ophthalmology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Department of Ophthalmology, Asklepios Hospital Nord-Heidberg, Hamburg, Germany.
Transl Vis Sci Technol. 2021 Aug 2;10(9):21. doi: 10.1167/tvst.10.9.21.
In a benchwork particle counting analytical evaluation, the number and type of particles in intravitreal injection formulations of three different agents against vascular endothelial growth factor were investigated.
Commercially available ready-to-use aflibercept and brolucizumab glass syringes, vials containing bevacizumab (off-label use in ophthalmology), and repackaged ready-to-use plastic syringes containing bevacizumab were tested without filtration. Total visible, subvisible, and nanoparticles numbers and size distributions were quantified using light obscuration, flow imaging, resonant mass measurement (RMM), tunable resistive pulse sensing, and dynamic light scattering.
Repackaged bevacizumab showed overall low particle numbers, aflibercept showed high numbers of micrometer sized particles but low nanoparticle numbers, brolucizumab showed low to moderate numbers of micrometer sized particles but high nanoparticle numbers. RMM measurements identified particles in the nanometer range as either proteinaceous or silicon oil; the nature of the other particles was not further evaluated.
Repackaged bevacizumab shows no inferior particle quality compared to ready-to-use products. It is relevant to study nanoparticle load of the products as the micrometer-sized particle numbers do not in all cases correlate to nanoparticle counts. Particularly for the high concentration product Beovu (brolucizumab), high nanoparticle numbers were found despite low numbers of micrometer sized particles. Silicone oil droplets did not account for high particle numbers as the measured numbers were low.
Different side effects are registered in different frequencies with different intravitreal anti-VEGF-drugs and syringes, which are applied by injection by small 30G needles through the sclera directly to the intravitreal cavity. The study of nanoparticles and silicone oil droplets may be able to contribute to narrowing down the causes.
在一项工作台粒子计数分析评估中，研究了三种不同血管内皮生长因子抑制剂的玻璃安瓿制剂和预装塑料注射器制剂中的粒子数量和类型。
对市售即用型阿柏西普和布罗利珠单抗玻璃注射器、含有贝伐珠单抗的小瓶（眼科超适应证使用）以及重新包装的即用型塑料注射器进行了测试，未进行过滤。使用光遮挡、流成像、共振质量测量（RMM）、可调电阻脉冲感应和动态光散射法对总可见粒子、亚可见粒子和纳米粒子数量及其粒径分布进行定量分析。
重新包装的贝伐珠单抗总体上显示出低粒子数量，阿柏西普显示出大量微米级粒子但低纳米粒子数量，布罗利珠单抗显示出低至中等数量的微米级粒子但高纳米粒子数量。RMM 测量结果表明，纳米级粒子要么是蛋白质，要么是硅油；其他粒子的性质没有进一步评估。
与即用型产品相比，重新包装的贝伐珠单抗显示出相同的优异粒子质量。研究产品的纳米粒子负载很重要，因为在所有情况下，微米级粒子数量都不一定与纳米粒子计数相关。特别是对于高浓度产品 Beovu（布罗利珠单抗），尽管微米级粒子数量低，但仍发现了高纳米粒子数量。由于测量的硅酮油滴数量较低，因此硅酮油滴并不是造成高粒子数量的原因。
在一项工作台粒子计数分析评估中，研究了三种不同血管内皮生长因子抑制剂的玻璃安瓿制剂和预装塑料注射器制剂中的粒子数量和类型。
对市售即用型阿柏西普和布罗利珠单抗玻璃注射器、含有贝伐珠单抗的小瓶（眼科超适应证使用）以及重新包装的即用型塑料注射器进行了测试，未进行过滤。使用光遮挡、流成像、共振质量测量（RMM）、可调电阻脉冲感应和动态光散射法对总可见粒子、亚可见粒子和纳米粒子数量及其粒径分布进行定量分析。
重新包装的贝伐珠单抗总体上显示出低粒子数量，阿柏西普显示出大量微米级粒子但低纳米粒子数量，布罗利珠单抗显示出低至中等数量的微米级粒子但高纳米粒子数量。RMM 测量结果表明，纳米级粒子要么是蛋白质，要么是硅油；其他粒子的性质没有进一步评估。
与即用型产品相比，重新包装的贝伐珠单抗显示出相同的优异粒子质量。研究产品的纳米粒子负载很重要，因为在所有情况下，微米级粒子数量都不一定与纳米粒子计数相关。特别是对于高浓度产品 Beovu（布罗利珠单抗），尽管微米级粒子数量低，但仍发现了高纳米粒子数量。由于测量的硅酮油滴数量较低，因此硅酮油滴并不是造成高粒子数量的原因。
