by Bob Benchley
The Diabetes Research Institute (DRI) at the University of Miami Miller School of Medicine, in a collaborative study with seven other institutions around the world, has demonstrated the feasibility of large-scale production of pancreatic islet cells by multiple manufacturing sites using a standardized process.
Their report, “NIH-sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities,” was published as the cover story in the November issue of Diabetes. DRI Director Camillo Ricordi, M.D. (pictured), was first author of the article. A high-definition photograph of purified human islets used for transplantation in subjects with the most severe forms of diabetes was selected as the cover image of the prestigious journal.
A commentary, “Human Pancreatic Islet Production: From Research Protocols to Standardized Multicenter Manufacturing,” was published in the same issue. Written by Federico Bertuzzi, M.D., who heads the Islet Transplant Program at Ospedale Niguarda Ca’ Granda, a public hospital in Milan, Italy, and his colleague, transplant surgeon Luciano Gregorio De Carlis, M.D., the commentary called the standards developed by Ricordi and his collaborators a “landmark and a new standard for future reference.”
“Previous clinical trials studying subjects with unstable type 1 diabetes have shown that pancreatic beta-cell function can be restored by islet transplantation for 10 years or more,” said Ricordi, who is also the Stacy Joy Goodman Professor of Surgery, Distinguished Professor of Medicine, Professor of Biomedical Engineering, Microbiology and Immunology, and Director of the UM Cell Transplant Program. “The difficulty with those prior trials has been the small number of subjects and the difficulty to compare results between transplant centers because of a lack of standardization of the process for manufacturing of insulin-producing cell products.”
The eight manufacturing facilities that participated in the Clinical Islet Transplantation Consortium jointly developed and implemented a harmonized process to manufacture 75 lots of an allogeneic purified human pancreatic islet product that was evaluated in a phase 3 trial through transplantation into 48 enrolled subjects with type 1 diabetes. The multicenter clinical trial was a success, with 88 percent of transplanted subjects achieving the primary endpoint at one year post-transplant and with significant improvement in all measures of glycemic control. Central to the manufacturing was the automated method for islet isolation developed by Ricordi in 1988. Although he patented the process, and the pancreas is processed in a digestion-filtration apparatus known as the Ricordi Chamber, Ricordi long ago renounced royalties and financial benefits, believing that open access would speed translational research and the path to an eventual cure.
“My philosophy has always been to share information and encourage scientific collaboration without borders,” said Ricordi. “Each small step improves our ability to treat some of the most severe cases of diabetes, and I am proud that South Florida has been central to making knowledge and technology available worldwide for many years. We will continue to refine the manufacturing process as we move toward FDA approval of what could become the first FDA approved biologically active, complex cellular product.”
Other Miller School researchers working on the manufacturing project with Ricordi included Elina Linetsky, Ph.D., Director of the cGMP Human Cell Processing Facility (HCPF) at the DRI, and the entire cGMP HCPF team, including Aisha Khan, M.B.A., now Executive Director of Laboratory Operations at the Interdisciplinary Stem Cell Institute.