Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, the Netherlands; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.
Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.
J Pharm Sci. 2024 Apr;113(4):1029-1037. doi: 10.1016/j.xphs.2023.10.015. Epub 2023 Oct 13.
Monoclonal antibodies (mAbs) can be damaged during the aseptic compounding process, with aggregation being the most prevalent form of degradation. Protein aggregates represent one of several risk factors for undesired immunogenicity of mAbs, which can potentially lead to severe adverse drug reactions and less effective treatments. Since data on aggregate and particle formation by robotic compounding is missing, we aimed to compare the antibody stability between robotic- and manual compounding of mAbs with regard to formation of (sub)visible aggregates. Infliximab and trastuzumab were compounded into infusion bags with the APOTECAchemo robot or manually by nurses or pharmacy technicians. The products were analyzed by quantifying (sub)visible particles with nanoparticle tracking analysis, dynamic light scattering (DLS), light obscuration, micro-flow imaging, high pressure size exclusion chromatography (HP-SEC), and visual inspection. HP-SEC showed high percentages monomers in trastuzumab (99.4 % and 99.4 %) and infliximab (99.5 % and 99.6 %) infusion bags for both manual and robotic compounding, respectively. DLS indicated more consistent and reproducible results with robotic compounding, and confirmed monodisperse samples with a higher polydispersity index for manual compounding (0.16, interquartile range; IQR 0.14-0.18) compared to robotic compounding (0.12, IQR 0.11-0.15). This study shows that the studied compounding methods had a minor impact on the number of aggregates and particles, and that robotic compounding of mAbs provided at least similar quality as manual compounding.
单克隆抗体 (mAbs) 在无菌调配过程中可能会受损，其中聚集是最常见的降解形式。蛋白质聚集体是 mAbs 产生非预期免疫原性的几个风险因素之一，这可能导致严重的药物不良反应和治疗效果降低。由于缺乏关于机器人调配中聚集体和颗粒形成的数据，我们旨在比较机器人和手动调配 mAbs 时形成（亚）可见聚集体的抗体稳定性。英夫利昔单抗和曲妥珠单抗用 APOTECAchemo 机器人或护士或药剂师手动调配到输液袋中。通过纳米颗粒跟踪分析、动态光散射 (DLS)、光遮挡、微流成像、高压尺寸排除色谱 (HP-SEC) 和目视检查来分析产品。HP-SEC 显示手动和机器人调配的曲妥珠单抗（分别为 99.4%和 99.4%）和英夫利昔单抗（分别为 99.5%和 99.6%）输液袋中单体的百分比很高。DLS 表明机器人调配的结果更一致且可重现，并通过更高的多分散指数确认了单分散样品，而手动调配的多分散指数为 0.16（四分位距；IQR 0.14-0.18），而机器人调配的多分散指数为 0.12（IQR 0.11-0.15）。这项研究表明，所研究的调配方法对聚集体和颗粒的数量影响较小，并且机器人调配 mAbs 提供的质量至少与手动调配相当。
