|Authors||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 DE, Linetsky E, Luo X, Markmann JF, Naji A, Korsgren O, Oberholzer J, Turgeon NA, Brandhorst D, Friberg AS, Lei J, Wang LJ, Wilhelm JJ, Willits J, Zhang X, Hering BJ, Posselt AM, Shapiro AM|
|Publish Date||2016 Jul 27|
Eight manufacturing facilities participating in the NIH-sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for manufacture of the 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 (MPBR), standard operating procedures including acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis (CoA) and test methods. The process was compliant with current Good Manufacturing Practices (cGMP) and Good Tissue Practices (cGTP).This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results of the manufacturing process including lot release. The results demonstrated the feasibility of implementing a harmonized process at multiple facilities for manufacture of a complex cellular product. The quality systems, regulatory and operational strategies developed by the CIT consortium yielded product lots that met the pre-specified characteristics of safety, purity, potency and identity, and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no case of primary non-function were observed.