National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities.
Ricordi C., Goldstein JS., Balamurugan AN., Szot GL., Kin T., Liu C., Czarniecki CW., Barbaro B., Bridges ND., Cano J., Clarke WR., Eggerman TL., Hunsicker LG., Kaufman DB., Khan A., Lafontant D-E., Linetsky E., Luo X., Markmann JF., Naji A., Korsgren O., Oberholzer J., Turgeon NA., Brandhorst D., Chen X., Friberg AS., Lei J., Wang L-J., Wilhelm JJ., Willits J., Zhang X., Hering BJ., Posselt AM., Stock PG., Shapiro AMJ., Chen X.
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.