Roesch Alexandra, Zölls Sarah, Stadler Daniela, Helbig Constanze, Wuchner Klaus, Kersten Gideon, Hawe Andrea, Jiskoot Wim, Menzen Tim
Coriolis Pharma, Fraunhoferstr. 18 b, 82152 Martinsried, Germany; Leiden Academic Centre for Drug Research (LACDR), Leiden University, PO Box 9502, 2300, RA, Leiden, the Netherlands.
Coriolis Pharma, Fraunhoferstr. 18 b, 82152 Martinsried, Germany.
J Pharm Sci. 2022 Apr;111(4):933-950. doi: 10.1016/j.xphs.2021.12.011. Epub 2021 Dec 14.
Particles in biopharmaceutical formulations remain a hot topic in drug product development. With new product classes emerging it is crucial to discriminate particulate active pharmaceutical ingredients from particulate impurities. Technical improvements, new analytical developments and emerging tools (e.g., machine learning tools) increase the amount of information generated for particles. For a proper interpretation and judgment of the generated data a thorough understanding of the measurement principle, suitable application fields and potential limitations and pitfalls is required. Our review provides a comprehensive overview of novel particle analysis techniques emerging in the last decade for particulate impurities in therapeutic protein formulations (protein-related, excipient-related and primary packaging material-related), as well as particulate biopharmaceutical formulations (virus particles, virus-like particles, lipid nanoparticles and cell-based medicinal products). In addition, we review the literature on applications, describe specific analytical approaches and illustrate advantages and drawbacks of currently available techniques for particulate biopharmaceutical formulations.
生物制药制剂中的颗粒仍然是药品开发中的一个热门话题。随着新的产品类别不断涌现，区分颗粒状活性药物成分与颗粒状杂质至关重要。技术改进、新的分析进展以及新兴工具（如机器学习工具）增加了针对颗粒产生的信息量。为了正确解释和判断所生成的数据，需要对测量原理、合适的应用领域以及潜在的局限性和陷阱有透彻的理解。我们的综述全面概述了过去十年中出现的用于治疗性蛋白质制剂（与蛋白质相关、与辅料相关和与一级包装材料相关）中的颗粒杂质以及颗粒状生物制药制剂（病毒颗粒、病毒样颗粒、脂质纳米颗粒和细胞治疗产品）的新型颗粒分析技术。此外，我们回顾了有关应用的文献，描述了具体的分析方法，并阐述了目前可用的颗粒状生物制药制剂技术的优缺点。
