Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
Blood Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
Transfusion. 2019 Aug;59(8):2506-2518. doi: 10.1111/trf.15349. Epub 2019 May 28.
As cell and gene therapies (CGT) assume center stage in early-phase clinical trials for several acute and chronic diseases, there is heightened interest in the standardization and automation of manufacturing processes in preparation for commercialization. Toward this goal, a hybrid and oftentimes geographically separated model comprising regional cell procurement and infusion facilities and a centralized cell manufacturing unit is gaining traction in the field. Although CGT processing facilities in academic institutions are not involved directly in the manufacturing of these therapies, they must be prepared to collaborate with commercial or contract manufacturing organizations (CMOs) and be ready to address several supply-chain challenges that have emerged for autologous and allogeneic CGT. Academic center cell-processing facilities must handle many events up- and downstream of manufacturing such as donor screening, cell collection, product labeling, cryopreservation, transportation, and thaw infusion. These events merit closer evaluation in the context of multifacility manufacturing since standard procedures have yet to be established. Based on our institutional experience, we summarize logistical challenges encountered in the handling and distribution of CGT products in early phase studies, specifically those involving CMO (outsourced) manufacturing. We also make recommendations to standardize processes unique to the CGT supply chain, emphasizing the need to maintain needle-to-needle traceability from product collection to infusion. These guidelines will inform the development of more complex supply-chain models for larger-scale cell and gene therapeutics.
随着细胞和基因疗法 (CGT) 在几种急性和慢性疾病的早期临床试验中占据中心地位，人们对制造工艺的标准化和自动化越来越感兴趣，以便为商业化做好准备。为此，一种混合的、通常是地域上分离的模型正在该领域得到关注，该模型由区域细胞采购和输注设施以及集中的细胞制造单元组成。虽然学术机构的 CGT 处理设施不直接参与这些疗法的制造，但它们必须准备好与商业或合同制造组织 (CMO) 合作，并准备好应对异体和同种异体 CGT 出现的几个供应链挑战。学术中心的细胞处理设施必须处理制造过程上下游的许多事件，如供体筛选、细胞采集、产品标记、冷冻保存、运输和解冻输注。由于尚未建立标准程序，这些事件在多设施制造的背景下值得更仔细的评估。基于我们机构的经验，我们总结了在早期研究中处理和分发 CGT 产品时遇到的物流挑战，特别是涉及 CMO（外包）制造的情况。我们还提出了标准化 CGT 供应链独特流程的建议，强调需要从产品采集到输注保持针到针的可追溯性。这些准则将为更大规模的细胞和基因治疗提供更复杂的供应链模型的开发提供信息。
