Jayaraman Premkumar, Lim Ryan, Ng Jacqueline, Vemuri Mohan C
Thermo Fisher Scientific, Singapore, Singapore.
Thermo Fisher Scientific, Frederick, MD, United States.
Front Cell Dev Biol. 2021 Apr 13;9:648472. doi: 10.3389/fcell.2021.648472. eCollection 2021.
Human mesenchymal stromal cell (hMSC) therapy has been gaining immense interest in regenerative medicine and quite recently for its immunomodulatory properties in COVID-19 treatment. Currently, the use of hMSCs for various diseases is being investigated in >900 clinical trials. Despite the huge effort, setting up consistent and robust scalable manufacturing to meet regulatory compliance across various global regions remains a nagging challenge. This is in part due to a lack of definitive consensus for quality control checkpoint assays starting from cell isolation to expansion and final release criterion of clinical grade hMSCs. In this review, we highlight the bottlenecks associated with hMSC-based therapies and propose solutions for consistent GMP manufacturing of hMSCs starting from raw materials selection, closed and modular systems of manufacturing, characterization, functional testing, quality control, and safety testing for release criteria. We also discuss the standard regulatory compliances adopted by current clinical trials to broaden our view on the expectations across different jurisdictions worldwide.
人间充质基质细胞（hMSC）疗法在再生医学领域引起了极大关注，最近因其在治疗新冠肺炎中的免疫调节特性而备受瞩目。目前，超过900项临床试验正在研究hMSCs在各种疾病中的应用。尽管付出了巨大努力，但建立一致且强大的可扩展生产流程以满足全球不同地区的监管要求仍然是一个棘手的挑战。部分原因是从细胞分离到临床级hMSCs的扩增及最终放行标准，缺乏关于质量控制检查点检测的明确共识。在本综述中，我们强调了基于hMSC疗法相关的瓶颈，并从原材料选择、封闭和模块化生产系统、特性鉴定、功能测试、质量控制以及用于放行标准的安全性测试等方面，提出了实现hMSCs一致的药品生产质量管理规范（GMP）生产的解决方案。我们还讨论了当前临床试验所采用的标准监管要求，以拓宽我们对全球不同司法管辖区期望的认识。
