BACKGROUND AIMS At the frontier of transfusion medicine and transplantation, the field of cellular therapy is emerging. Most novel cellular therapy products are produced under investigational protocols with no clear standardization across cell processing centers. Thus, the purpose of this study was to uncover any variations in manufacturing practices for similar cellular therapy products across different cell processing laboratories worldwide. METHODS An exploratory survey that was designed to identify variations in manufacturing practices in novel cellular therapy products was sent to cell processing laboratory directors worldwide. The questionnaire focused on the manufacturing life cycle of different cell therapies (i.e., collection, purification, in vitro expansion, freezing and storage, and thawing and washing), as well as the level of regulations followed to process each product type. RESULTS The majority of the centers processed hematopoietic progenitor cells (HPCs) from peripheral blood (n = 18), bone marrow (n = 16) or cord blood (n = 19), making HPCs the most commonly processed cells. The next most commonly produced cellular therapies were lymphocytes (n = 19) followed by mesenchymal stromal cells (n = 14), dendritic cells (n = 9) and natural killer (NK) cells (n = 9). A minority of centers (<5) processed pancreatic islet cells (n = 4), neural cells (n = 3) and induced-pluripotent stem cells (n = 3). Thirty-two laboratories processed products under an investigational status, for either phase I/II (n = 27) or phase III (n = 17) clinical trials. If purification methods were used, these varied for the type of product processed and by institution. Environmental monitoring methods also varied by product type and institution. CONCLUSION This exploratory survey shows a wide variation in cellular therapy manufacturing practices across different cell processing laboratories. A better understanding of the effect of these variations on the quality of these cell-based therapies will be important to assess for further process evaluation and development.

中文翻译：

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新型细胞治疗产品制造的变化

背景目标在输血医学和移植的前沿，细胞治疗领域正在兴起。大多数新型细胞治疗产品是根据研究协议生产的，没有跨细胞处理中心的明确标准化。因此，本研究的目的是揭示全球不同细胞处理实验室中类似细胞治疗产品的制造实践中的任何差异。方法 一项旨在确定新型细胞治疗产品制造实践变化的探索性调查已发送给全球细胞处理实验室主任。问卷重点关注不同细胞疗法的制造生命周期（即收集、纯化、体外扩增、冷冻和储存以及解冻和洗涤），以及处理每种产品类型所遵循的法规水平。结果 大多数中心处理来自外周血 (n = 18)、骨髓 (n = 16) 或脐带血 (n = 19) 的造血祖细胞 (HPC)，使 HPC 成为最常处理的细胞。其次最常见的细胞疗法是淋巴细胞（n = 19），其次是间充质基质细胞（n = 14）、树突细胞（n = 9）和自然杀伤（NK）细胞（n = 9）。少数中心 (<5) 处理胰岛细胞 (n = 4)、神经细胞 (n = 3) 和诱导多能干细胞 (n = 3)。32 个实验室处理处于研究状态的产品，用于 I/II 期（n = 27）或 III 期（n = 17）临床试验。如果使用纯化方法，这些方法因加工产品的类型和机构而异。环境监测方法也因产品类型和机构而异。结论 这项探索性调查显示，不同细胞处理实验室的细胞疗法制造实践存在很大差异。更好地了解这些变化对这些基于细胞的疗法质量的影响对于评估进一步的工艺评估和开发非常重要。