National Institutes of Health–Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities

Abstract

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.

The impact of cell surface PEGylation and short-course immunotherapy on islet graft survival in an allogeneic murine model

“…Why these two grafts rejected, while the others did not, cannot be attributed to any known factors associated with the islet isolation or recipient group. This is not unlike clinical islet transplantation, where no correlation, to date, has been found between a pre-transplant islet assay(s) or the recipient’s profile and the overall transplant outcome or graft duration [76]. Thus, identification of such factors is the focus of numerous research studies.…”

Strategies in Preventing Diabetes after Pancreatectomy Using Islet Auto- and Allo-Transplantation

“…This concern on pancreatic study, aimed at developing a common standard to follow across different islet isolation centers. Islets isolated under this study were successfully implanted in 48 patients with no adverse effects, thus illustrating the importance of a national standard on islet isolation to ensure good clinical outcome [52].…”

Recent progress in the use and tracking of transplanted islets as a personalized treatment for type 1 diabetes

“…The process was performed in eight different manufacturing facilities with a common master production batch record, islet product specifications, certificate of analysis, and test methods, all of them compliant with current good manufacturing practices. The report proved that it is feasible to implement a standardized process at multiple facilities for obtaining a complex cellular product with the desired characteristics and function after transplantation [32]. …”