Elsallab Magdi, Bourgeois Florence, Maus Marcela V
Harvard-MIT Center for Regulatory Science, Harvard Medical School, Boston, Massachusetts; Cellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
Harvard-MIT Center for Regulatory Science, Harvard Medical School, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Computational Health Informatics Program, Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
Transplant Cell Ther. 2024 Jun;30(6):626.e1-626.e11. doi: 10.1016/j.jtct.2024.03.016. Epub 2024 Mar 16.
The utilization of the human immune system as a therapeutic modality has materialized in the form of novel biologics known as immune effector cells (IECs). However, currently approved IECs rely on autologous cells for manufacturing that are funneled through costly centralized supply chains leading to long wait times and potentially increased mortality. Alternative models for manufacturing at or near the point-of-care in a distributed and local approach are being proposed to overcome such a bottleneck. Cell processing facilities for minimally manipulated products, as well as academic good manufacturing practice facilities, are being considered for such manufacturing tasks. However, the infrastructure and the practices of these facilities remains unstudied. Here, we surveyed the cell processing facilities accredited by the Foundation for Accreditation of Cellular Therapy (FACT) in the United States to better understand their preparedness for local manufacturing of IECs. A structured survey consisting of 40 items was distributed to the directors of 157 facilities. The survey evaluated 6 domains, including facility characteristics, quality practices, personnel, use of automation, experience with IECs, and the perception of the point-of-care model. Thirty-eight facilities completed the survey (24.2%). Most facilities were involved in handling IEC products (35/38, 92.1%), and the majority had infrastructure to support basic operations and quality control such as viability (36/36, 100%), identity (33/36, 91.7%), and sterility (33/36, 91.7%). The quality practices varied among the facilities depending on the types of products processed. A slight majority implemented automation in their workflows (22/38, 57.9%). Facilities expressed a general interest in adopting point-of-care models (23/38, 61%), with financial and human resources identified as the most significant constraints. In conclusion, FACT-accredited cell processing facilities may provide the infrastructure required for local manufacturing. However, there is a need for standardization and minimum quality requirements to effectively implement such models.
将人体免疫系统用作一种治疗方式已具体体现为一种名为免疫效应细胞（IECs）的新型生物制品。然而，目前获批的免疫效应细胞依赖自体细胞进行生产，这些细胞需通过成本高昂的集中供应链输送，导致等待时间漫长，且可能增加死亡率。为克服这一瓶颈，人们正提议采用分布式和本地化的方法在医疗现场或其附近进行生产。用于最低限度操作产品的细胞处理设施以及学术性良好生产规范设施正被考虑用于此类生产任务。然而，这些设施的基础设施和操作规范仍未得到研究。在此，我们对美国细胞治疗认证基金会（FACT）认可的细胞处理设施进行了调查，以更好地了解它们对免疫效应细胞本地化生产的准备情况。一项包含40个项目的结构化调查问卷被分发给157个设施的主管。该调查评估了6个领域，包括设施特征、质量规范、人员、自动化使用情况、免疫效应细胞相关经验以及对医疗现场模式的看法。38个设施完成了调查（24.2%）。大多数设施参与处理免疫效应细胞产品（35/38，92.1%），并且大多数具备支持基本操作和质量控制的基础设施，如活力检测（36/36，100%）、身份鉴定（33/36，91.7%）和无菌检测（33/36，91.7%）。质量规范因所处理产品的类型不同而在各设施间有所差异。略超过半数的设施在其工作流程中采用了自动化（22/38，57.9%）。各设施普遍表示有兴趣采用医疗现场模式（23/
38，61%），并认为资金和人力资源是最主要的制约因素。总之，获得FACT认可的细胞处理设施可能提供本地化生产所需的基础设施。然而，需要进行标准化并制定最低质量要求，以有效实施此类模式。
