Yao Yifan, Wen Xuemei, Pan Hongjuan, Chen Ziwei
National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry, Shanghai, China.
China State Institute of Pharmaceutical Industry, Shanghai, China.
Front Microbiol. 2025 Aug 18;16:1658366. doi: 10.3389/fmicb.2025.1658366. eCollection 2025.
Host cell proteins (HCPs) are process-related impurities derived from host organisms used for recombinant protein production in biopharmaceutical manufacturing. The generation of HCPs may lead to potential safety risks, such as immunogenicity, reduced drug efficacy and long-term side effects. Therefore, in the biopharmaceutical process, even trace amounts of HCPs need to be strictly regulated and controlled. The main bottlenecks associated with the detection of HCPs include a wide dynamic range of detection and instability of HCPs. Due to its high sensitivity and high resolution, mass spectrometry has attracted more and more attention in HCP detection, but it still cannot completely replace enzyme-linked immunosorbent assay (ELISA). The research in the future includes the development of more efficient sample pretreatment methods and data processing techniques to improve the sensitivity and accuracy of detection. At the same time, combined with risk assessment and process optimization, it is expected to further reduce the residual risk of HCP. This review discusses the sources, properties, pretreatment and detection of residual HCPs in therapeutic products, along with current regulatory considerations and future advancements.
宿主细胞蛋白（HCPs）是生物制药生产中用于重组蛋白生产的宿主生物体衍生的与工艺相关的杂质。HCPs的产生可能导致潜在的安全风险，如免疫原性、药物疗效降低和长期副作用。因此，在生物制药过程中，即使是痕量的HCPs也需要严格监管和控制。与HCPs检测相关的主要瓶颈包括检测的宽动态范围和HCPs的不稳定性。由于其高灵敏度和高分辨率，质谱在HCP检测中越来越受到关注，但它仍不能完全取代酶联免疫吸附测定（ELISA）。未来的研究包括开发更高效的样品预处理方法和数据处理技术，以提高检测的灵敏度和准确性。同时，结合风险评估和工艺优化，有望进一步降低HCP的残留风险。本综述讨论了治疗产品中残留HCPs的来源、性质、预处理和检测，以及当前的监管考虑和未来进展。
