National institutes of health-sponsored clinical islet transplantation consortium phase 3 trial: Manufacture of a complex cellular product at eight processing facilities

Camillo Ricordi, Julia S. Goldstein, A. N. Balamurugan, Gregory L. Szot, Tatsuya Kin, Chengyang Liu, Christine W. Czarniecki, Barbara Barbaro, Nancy D. Bridges, Jose Cano, William R. Clarke, Thomas L. Eggerman, Lawrence G. Hunsicker, Dixon B. Kaufman, Aisha Khan, David Erick Lafontant, Elina Linetsky, Xunrong Luo, James F. Markmann, Ali NajiOlle Korsgren, Jose Oberholzer, Nicole A. Turgeon, Daniel Brandhorst, Andrew S. Friberg, Ji Lei, Ling Jia Wang, Joshua J. Wilhelm, Jamie Willits, Xiaomin Zhang, Bernhard J. Hering, Andrew M. Posselt, Peter G. Stock, A. M James Shapiro

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3418-3428
Number of pages11
JournalDiabetes
Volume65
Issue number11
DOIs
StatePublished - Nov 1 2016

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Islets of Langerhans Transplantation
National Institutes of Health (U.S.)
Islets of Langerhans
Type 1 Diabetes Mellitus
Pancreas
Tissue Donors
Safety

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

National institutes of health-sponsored clinical islet transplantation consortium phase 3 trial : Manufacture of a complex cellular product at eight processing facilities. / Ricordi, Camillo; Goldstein, Julia S.; Balamurugan, A. N.; Szot, Gregory L.; Kin, Tatsuya; Liu, Chengyang; Czarniecki, Christine W.; Barbaro, Barbara; Bridges, Nancy D.; Cano, Jose; Clarke, William R.; Eggerman, Thomas L.; Hunsicker, Lawrence G.; Kaufman, Dixon B.; Khan, Aisha; Lafontant, David Erick; Linetsky, Elina; Luo, Xunrong; Markmann, James F.; Naji, Ali; Korsgren, Olle; Oberholzer, Jose; Turgeon, Nicole A.; Brandhorst, Daniel; Friberg, Andrew S.; Lei, Ji; Wang, Ling Jia; Wilhelm, Joshua J.; Willits, Jamie; Zhang, Xiaomin; Hering, Bernhard J.; Posselt, Andrew M.; Stock, Peter G.; Shapiro, A. M James.

In: Diabetes, Vol. 65, No. 11, 01.11.2016, p. 3418-3428.

Research output: Contribution to journalArticle

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, Stock, PG & Shapiro, AMJ 2016, 'National institutes of health-sponsored clinical islet transplantation consortium phase 3 trial: Manufacture of a complex cellular product at eight processing facilities', Diabetes, vol. 65, no. 11, pp. 3418-3428. https://doi.org/10.2337/db16-0234
Ricordi, Camillo ; Goldstein, Julia S. ; Balamurugan, A. N. ; Szot, Gregory L. ; Kin, Tatsuya ; Liu, Chengyang ; Czarniecki, Christine W. ; Barbaro, Barbara ; Bridges, Nancy D. ; Cano, Jose ; Clarke, William R. ; Eggerman, Thomas L. ; Hunsicker, Lawrence G. ; Kaufman, Dixon B. ; Khan, Aisha ; Lafontant, David Erick ; Linetsky, Elina ; Luo, Xunrong ; Markmann, James F. ; Naji, Ali ; Korsgren, Olle ; Oberholzer, Jose ; Turgeon, Nicole A. ; Brandhorst, Daniel ; Friberg, Andrew S. ; Lei, Ji ; Wang, Ling Jia ; Wilhelm, Joshua J. ; Willits, Jamie ; Zhang, Xiaomin ; Hering, Bernhard J. ; Posselt, Andrew M. ; Stock, Peter G. ; Shapiro, A. M James. / National institutes of health-sponsored clinical islet transplantation consortium phase 3 trial : Manufacture of a complex cellular product at eight processing facilities. In: Diabetes. 2016 ; Vol. 65, No. 11. pp. 3418-3428.
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AU - Ricordi, Camillo

AU - Goldstein, Julia S.

AU - Balamurugan, A. N.

AU - Szot, Gregory L.

AU - Kin, Tatsuya

AU - Liu, Chengyang

AU - Czarniecki, Christine W.

AU - Barbaro, Barbara

AU - Bridges, Nancy D.

AU - Cano, Jose

AU - Clarke, William R.

AU - Eggerman, Thomas L.

AU - Hunsicker, Lawrence G.

AU - Kaufman, Dixon B.

AU - Khan, Aisha

AU - Lafontant, David Erick

AU - Linetsky, Elina

AU - Luo, Xunrong

AU - Markmann, James F.

AU - Naji, Ali

AU - Korsgren, Olle

AU - Oberholzer, Jose

AU - Turgeon, Nicole A.

AU - Brandhorst, Daniel

AU - Friberg, Andrew S.

AU - Lei, Ji

AU - Wang, Ling Jia

AU - Wilhelm, Joshua J.

AU - Willits, Jamie

AU - Zhang, Xiaomin

AU - Hering, Bernhard J.

AU - Posselt, Andrew M.

AU - Stock, Peter G.

AU - Shapiro, A. M James

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