>For production of different monoclonal antibodies (mAbs), biopharmaceutical companies often use related upstream and downstream manufacturing processes. '/> Mass spectrometric evaluation of upstream and downstream process influences on host cell protein patterns in biopharmaceutical products
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Mass spectrometric evaluation of upstream and downstream process influences on host cell protein patterns in biopharmaceutical products

机译：对生物制药产品中宿主细胞蛋白质模式的上游和下游过程的质谱评价

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>For production of different monoclonal antibodies (mAbs), biopharmaceutical companies often use related upstream and downstream manufacturing processes. Such platforms are typically characterized regarding influence of upstream and downstream process (DSP) parameters on critical quality attributes (CQAs). CQAs must be monitored strictly by an adequate control strategy. One such process‐related CQA is the content of host cell protein (HCP) which is typically analyzed by immunoassay methods (e.g., HCP‐ELISA). The capacity of the immunoassay to detect a broad range of HCPs, relevant for the individual mAb‐production process should be proven by orthogonal proteomic methods such as 2D gel electrophoresis or mass spectrometry (MS). In particular MS has become a valuable tool to identify and quantify HCP in complex mixtures. We evaluate up‐ and DSP parameters of four different biopharmaceutical products, two different process variants, and one mock fermentation on the HCP pattern by shotgun MS analysis and ELISA. We obtained a similar HCP pattern in different cell culture fluid harvests compared to the starting material from the downstream process. During the downstream purification process of the mAbs, the HCP level and the number of HCP species significantly decreased, accompanied by an increase in diversity of the residual HCP pattern. Based on this knowledge, we suggest a control strategy that combines multi product ELISA for in‐process control and release analytics, and MS testing for orthogonal HCP characterization, to attain knowledge on the HCP level, clusters and species. This combination supports a control strategy for HCPs addressing safety and efficacy of biopharmaceutical products.
机译： >用于生产不同单克隆抗体（MAB），生物制药公司往往使用相关的上游和下游制造过程。这种平台通常表征关于上游和下游过程（DSP）参数对关键质量属性（CQAS）的影响。 CQA必须严格通过足够的控制策略监控。一种这样的工艺相关的CQA是宿主细胞蛋白（HCP）的含量，其通常通过免疫测定方法（例如HCP-ELISA）分析。通过正交蛋白质组学方法如2D凝胶电泳或质谱法（MS），应通过正交蛋白质组学方法（MS）等正交蛋白质组学方法来证明免疫测定的容量。特别是MS已成为识别和量化复杂混合物中HCP的有价值的工具。我们评估四种不同的生物制药产品，两种不同的工艺变体的DSP参数，并通过霰弹枪MS分析和ELISA对HCP模式进行一次模拟发酵。与来自下游工艺的起始材料相比，我们在不同细胞培养液收集中获得了类似的HCP模式。在MAb的下游净化过程中，HCP水平和HCP物种的数量显着降低，伴随着残留HCP模式的多样性增加。基于这种知识，我们建议将多产品ELISA用于内部过程控制和释放分析的控制策略，以及对正交HCP表征的MS测试，以获得对HCP水平，集群和物种的知识。该组合支持用于HCP的控制策略，用于解决生物制药产品的安全性和功效。

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  • 来源
    《Biotechnology Progress》 |2019年第3期|共12页
  • 作者

    Falkenberg Heiner; Waldera‐Lupa Daniel Michael; Vanderlaan Martin; Schwab Thomas; Krapfenbauer Kurt; Studts Joey Michael; Flad Thomas; Waerner Thomas;

  • 作者单位

    Protagen Protein Services GmbHBiotherapeutical AnalyticsDortmund Germany;

    Protagen Protein Services GmbHBiotherapeutical AnalyticsDortmund Germany;

    ConsultantAnalytical ChemistrySan Francisco California;

    Department of Analytical Development BiologicalsBoehringer Ingelheim Pharma GmbH &

    Co. KG Analytical Development BiologicalsBiberach Germany;

    Department of European AffairsEuropean Association for Predictive Preventive and Personalised MedicineVienna Austria;

    Department of Bioprocess Development BiologicalsBoehringer Ingelheim Pharma GmbH &

    Co. KG Bioprocess Development BiologicalsBiberach Germany;

    Protagen Protein Services GmbHBiotherapeutical AnalyticsDortmund Germany;

    Department of Analytical Development BiologicalsBoehringer Ingelheim Pharma GmbH &

    Co. KG Analytical Development BiologicalsBiberach Germany;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物科学;
  • 关键词

    biopharmaceuticals; ELISA; host cell protein; mass spectrometry; proteomics;

    机译：生物制药;ELISA;宿主细胞蛋白;质谱;蛋白质组学;

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