title: 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.
authors.affiliation: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL ricordi@miami.edu goldsteinj@niaid.nih.gov.
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD ricordi@miami.edu goldsteinj@niaid.nih.gov.
authors.forename: Julia S
authors.initials: JS
authors.lastname: Goldstein
authors.affiliation: Schulze Diabetes Institute and Department of Surgery, University of Minnesota, Minneapolis, MN.
authors.forename: A N
authors.initials: AN
authors.lastname: Balamurugan
authors.affiliation: Department of Surgery, University of California, San Francisco, San Francisco, CA.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Szot
authors.affiliation: Clinical Islet Transplant Program and Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kin
authors.affiliation: Institute for Diabetes, Obesity and Metabolism and Departments of Surgery and Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Chengyang
authors.initials: C
authors.lastname: Liu
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
authors.forename: Christine W
authors.initials: CW
authors.lastname: Czarniecki
authors.affiliation: Division of Transplantation, University of Illinois Hospital and Health Sciences System, Chicago, IL.
authors.forename: Barbara
authors.initials: B
authors.lastname: Barbaro
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Bridges
authors.affiliation: Division of Transplantation, Department of Surgery, Emory Transplant Center, Emory University, Atlanta, GA.
authors.forename: Jose
authors.initials: J
authors.lastname: Cano
authors.forename: William R
authors.initials: WR
authors.lastname: Clarke
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Eggerman
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Hunsicker
authors.affiliation: Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Dixon B
authors.initials: DB
authors.lastname: Kaufman
authors.affiliation: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL.
authors.forename: Aisha
authors.initials: A
authors.lastname: Khan
authors.forename: David-Erick
authors.initials: DE
authors.lastname: Lafontant
authors.affiliation: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL.
authors.forename: Elina
authors.initials: E
authors.lastname: Linetsky
authors.affiliation: Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Xunrong
authors.initials: X
authors.lastname: Luo
authors.affiliation: Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: James F
authors.initials: JF
authors.lastname: Markmann
authors.affiliation: Institute for Diabetes, Obesity and Metabolism and Departments of Surgery and Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Ali
authors.initials: A
authors.lastname: Naji
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.affiliation: Division of Transplantation, University of Illinois Hospital and Health Sciences System, Chicago, IL.
authors.forename: Jose
authors.initials: J
authors.lastname: Oberholzer
authors.affiliation: Division of Transplantation, Department of Surgery, Emory Transplant Center, Emory University, Atlanta, GA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Turgeon
authors.affiliation: Department of Clinical Immunology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brandhorst
authors.affiliation: Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Friberg
authors.affiliation: Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Ji
authors.initials: J
authors.lastname: Lei
authors.affiliation: Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Ling-Jia
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Schulze Diabetes Institute and Department of Surgery, University of Minnesota, Minneapolis, MN.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Wilhelm
authors.forename: Jamie
authors.initials: J
authors.lastname: Willits
authors.affiliation: Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Schulze Diabetes Institute and Department of Surgery, University of Minnesota, Minneapolis, MN.
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Hering
authors.affiliation: Department of Surgery, University of California, San Francisco, San Francisco, CA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Posselt
authors.affiliation: Department of Surgery, University of California, San Francisco, San Francisco, CA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Stock
authors.affiliation: Clinical Islet Transplant Program and Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: A M James
authors.initials: AM
authors.lastname: Shapiro
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007515:Islets of Langerhans; D016381:Islets of Langerhans Transplantation / Q000191:economics / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009316:National Institutes of Health (U.S.); D014481:United States; D055815:Young Adult