Materials Science, Durham, North Carolina, USA.
Cell Culture Development, Durham, North Carolina, USA.
Biotechnol Prog. 2020 Sep;36(5):e3004. doi: 10.1002/btpr.3004. Epub 2020 May 1.
Elemental metals are critical raw material attributes which can impact cell culture performance and associated therapeutic protein product quality profiles. Metals such as copper and manganese act as cofactors and reagents for numerous metabolic pathways which govern cell growth, protein expression, and glycosylation, thus mandating elemental monitoring. The growing complexity of modern cell culture media formulations adds additional opportunities for elemental variance and its associated impact risks. This article describes an analytical technique applying inductively coupled plasma mass spectrometry to characterize a list of common raw materials and media powders used in mammalian cell culture and therapeutic protein production. We aim to describe a method qualification approach suitable for biopharmaceutical raw materials. Furthermore, we present detailed profiles of many common raw materials and discuss trends in raw material subtypes. Finally, a case study demonstrating the impact of an unexpected source of raw material variation is presented along with recommendations for raw material elemental risk profiling and control.
元素金属是关键的原材料属性，会影响细胞培养性能和相关治疗性蛋白产品质量特性。铜和锰等金属作为许多代谢途径的辅助因子和试剂，这些代谢途径控制着细胞生长、蛋白质表达和糖基化，因此需要进行元素监测。现代细胞培养基配方的日益复杂增加了元素变化及其相关影响风险的更多机会。本文描述了一种应用电感耦合等离子体质谱分析技术来描述用于哺乳动物细胞培养和治疗性蛋白生产的常见原材料和培养基粉末的分析技术。我们旨在描述一种适合生物制药原材料的方法验证方法。此外，我们还呈现了许多常见原材料的详细特性，并讨论了原材料亚类的趋势。最后，我们提出了一个案例研究，展示了原材料变化的意外来源的影响，并就原材料元素风险分析和控制提出了建议。
