Ricordi Camillo, Goldstein Julia S, Balamurugan A N, Szot Gregory L, Kin Tatsuya, Liu Chengyang, Czarniecki Christine W, Barbaro Barbara, Bridges Nancy D, Cano Jose, Clarke William R, Eggerman Thomas L, Hunsicker Lawrence G, Kaufman Dixon B, Khan Aisha, Lafontant David-Erick, Linetsky Elina, Luo Xunrong, Markmann James F, Naji Ali, Korsgren Olle, Oberholzer Jose, Turgeon Nicole A, Brandhorst Daniel, Chen Xiaojuan, Friberg Andrew S, Lei Ji, Wang Ling-Jia, Wilhelm Joshua J, Willits Jamie, Zhang Xiaomin, Hering Bernhard J, Posselt Andrew M, Stock Peter G, Shapiro A M James, Chen Xiaojuan
Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Diabetes. 2016 Nov;65(11):3418-3428. doi: 10.2337/db16-0234. Epub 2016 Jul 27.
Eight manufacturing facilities participating in the National Institutes of Health-sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed.
八家参与美国国立卫生研究院资助的临床胰岛移植（CIT）联盟的生产设施，共同开发并实施了一套统一流程，用于生产在1型糖尿病受试者的3期试验中评估的同种异体纯化人胰岛（PHPI）产品。生产过程由一份通用的主生产批次记录、标准操作规程控制，这些规程包括对已故供体器官胰腺和关键原材料的验收标准、PHPI产品规格、分析证书和测试方法。该流程符合现行良好生产规范和现行良好组织规范。本报告描述了75个PHPI临床批次的生产过程，并总结了结果，包括批次放行。结果证明了在多个设施中实施统一流程生产复杂细胞产品的可行性。CIT联盟开发的质量体系以及监管和运营策略，生产出的产品批次符合预先规定的安全性、纯度、效力和同一性特征，并成功移植到48名受试者体内。未观察到与产品相关的不良事件，也未出现原发性无功能病例。
