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.

中文翻译：

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用于过程风险分析的细胞培养原材料中的元素金属差异。

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的治疗性蛋白质产品质量概况。铜和锰等金属充当众多代谢途径的辅助因子和试剂，这些途径控制细胞生长、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日益复杂，增加了元素变异及其相关影响风险的机会。本文介绍了一种应用电感耦合等离子体质谱法来表征哺乳动物细胞培养和治疗性蛋白质生产中使用的一系列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用于生物制药原材料的方法认证方法。此外，我们提供了许多常见原材料的详细概况，并讨论了原材料子类型的趋势。最后，展示了一个案例研究，展示了原材料变化的意外来源的影响，以及对原材料元素风险分析和控制的建议。