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

Journal Article (Clinical Trial, Phase III;Journal Article)

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.

Full Text

Duke Authors

Cited 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, 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

Published Date

  • November 2016

Published In

Volume / Issue

  • 65 / 11

Start / End Page

  • 3418 - 3428

PubMed ID

  • 27465220

Pubmed Central ID

  • PMC5079635

Electronic International Standard Serial Number (EISSN)

  • 1939-327X

Digital Object Identifier (DOI)

  • 10.2337/db16-0234


  • eng

Conference Location

  • United States