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

TLDR

The manufacturing process complied with Current Good Manufacturing Practices and Current Good Tissue Practices. This report details the manufacturing of 75 allogeneic purified human pancreatic islet lots and summarizes their release results. Eight NIH‑sponsored CIT Consortium facilities jointly developed a harmonized process, governed by a common master production batch record and SOPs that set acceptance criteria for donor pancreata, raw materials, product specifications, certificates of analysis, and test methods. The harmonized process proved feasible, yielding 75 PHPI lots that met safety, purity, potency, and identity criteria and were successfully transplanted into 48 subjects with no product‑attributable adverse events or primary nonfunction.

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.