Life Science, Process Solutions, Merck Ltd. (An Affiliate of Merck KGaA, Darmstadt, Germany), Tokyo, Japan.
Independent Consultant, Sudbury, Massachusetts, USA.
Biotechnol Prog. 2024 Jul-Aug;40(4):e3448. doi: 10.1002/btpr.3448. Epub 2024 Mar 13.
Host cell proteins (HCPs) are process-related impurities in a therapeutic protein expressed using cell culture technology. This review presents biopharmaceutical industry trends in terms of both HCPs in the bioprocessing of monoclonal antibodies (mAbs) and the capabilities for HCP clearance by downstream unit operations. A comprehensive assessment of currently implemented and emerging technologies in the manufacturing processes with extensive references was performed. Meta-analyses of published downstream data were conducted to identify trends. Improved analytical methods and understanding of "high-risk" HCPs lead to more robust manufacturing processes and higher-quality therapeutics. The trend of higher cell density cultures leads to both higher mAb expression and higher HCP levels. However, HCP levels can be significantly reduced with improvements in operations, resulting in similar concentrations of approx. 10 ppm HCPs. There are no differences in the performance of HCP clearance between recent enhanced downstream operations and traditional batch processing. This review includes best practices for developing improved processes.
宿主细胞蛋白（HCP）是使用细胞培养技术表达的治疗性蛋白中的工艺相关杂质。本综述介绍了单克隆抗体（mAb）生物工艺中 HCP 的生物制药行业趋势，以及下游单元操作对 HCP 清除的能力。对制造工艺中目前实施和新兴技术进行了广泛参考的全面评估。对已发表的下游数据进行了荟萃分析，以确定趋势。改进的分析方法和对“高风险”HCP 的理解导致了更稳健的制造工艺和更高质量的治疗药物。更高的细胞密度培养的趋势导致更高的 mAb 表达和更高的 HCP 水平。然而，通过改进操作，HCP 水平可以显著降低，导致约 10ppm HCP 的浓度相似。最近增强的下游操作与传统的批量处理之间在 HCP 清除性能上没有差异。本综述包括开发改进工艺的最佳实践。
