Coye Lisette, Jones Marisa A, Gaza-Bulseco Georgeen, Chitikila Carmelata, Clavier Severine, Fougeron Delphine, Grimaldi Christine, Hurkmans Karen, Hutchinson Richard, Kellogg Brenda, Liu Xinrong, Palackal Nisha, Tank Mahima, Valax Pascal, Waerner Thomas, Wang Fengqiang, Zhang Ying, Zhao Yiwei, Sloan Sapphire, de Zafra Christina Zuch
Pfizer Inc., Pharmaceutical Sciences, Bothell, Washington, USA.
GSK, Collegeville, Pennsylvania, USA.
Biotechnol Bioeng. 2025 Aug 4. doi: 10.1002/bit.70029.
Host cell proteins (HCP) are process-related impurities that can co-purify with therapeutic proteins. Some HCP impurities potentially can have an impact on patient safety (immunogenicity or toxicity), efficacy, and/or product quality. It is important to reduce the levels of HCP impurities with a well-controlled manufacturing process and to monitor levels with a suitable analytical assay. Biopharmaceutical companies are now routinely using mass spectrometry to identify HCPs which are present in process intermediates and potentially in bulk drug substances and using the data to make decisions to continuously improve their processes and mitigate the potential risk to patients. Some companies perform identification of HCPs starting from the nonclinical stage of development, while others perform HCP identification at later stages or as a part of root cause analysis for identified HCP ELISA-related issues, process, and product quality or safety concerns. No matter the approach, a comprehensive risk assessment framework for identified HCPs is needed to support decision-making during development and is expected by regulators to ensure a safe and efficacious drug product. In this paper the BioPhorum Development Group HCP Workstream has brought together a team of industry experts to build upon existing risk assessment frameworks (e.g., de Zafra et al., 2015) and developed recommendations for assessment of clinical safety risks upon identification of individual HCPs, incorporating regulatory considerations and industry experience and using a real-world case study to illustrate the use of the updated frameworks. Key recommendations include conducting clinical risk assessment alongside product quality risk assessment following individual HCP identification and quantitation; focusing on biological activity and immunogenicity for any HCPs of concern; and communicating and collaborating effectively across functions to enable a comprehensive risk assessment.
宿主细胞蛋白（HCP）是与生产过程相关的杂质，可与治疗性蛋白共同纯化。一些HCP杂质可能会对患者安全（免疫原性或毒性）、疗效和/或产品质量产生影响。通过良好控制的生产工艺降低HCP杂质水平，并使用合适的分析方法监测其水平非常重要。生物制药公司现在通常使用质谱法来识别存在于工艺中间体以及可能存在于原料药中的HCP，并利用这些数据来做出决策，以持续改进其工艺并降低对患者的潜在风险。一些公司从非临床研发阶段就开始进行HCP的识别，而其他公司则在后期阶段进行HCP识别，或将其作为已识别的HCP ELISA相关问题、工艺、产品质量或安全问题的根本原因分析的一部分。无论采用何种方法，都需要一个针对已识别HCP的全面风险评估框架，以支持研发过程中的决策制定，并且监管机构期望通过该框架确保药品的安全性和有效性。在本文中，生物制药发展集团HCP工作流汇集了一组行业专家，在现有风险评估框架（例如de Zafra等人，2015年）的基础上进行构建，并针对识别出单个HCP后评估临床安全风险制定了建议，纳入了监管考量和行业经验，并通过一个实际案例研究来说明更新框架的使用。关键建议包括在识别和定量单个HCP后，同时进行临床风险评估和产品质量风险评估；关注任何相关HCP的生物活性和免疫原性；以及跨职能部门进行有效沟通与协作，以实现全面的风险评估。
