The demise of islet allotransplantation in the United States: A call for an urgent regulatory update

Abstract

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state‐of‐the‐art in clinical or technical practices. In the US, islets are considered biologic drugs and “more than minimally manipulated” human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as “minimally manipulated tissue” and not regulated as a drug, which has led to islet allotransplantation (allo‐ITx) becoming a standard‐of‐care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo‐ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo‐ITx in the United States.

Arguments against the Requirement of a Biological License Application for Human Pancreatic Islets: The Position Statement of the Islets for US Collaborative Presented during the FDA Advisory Committee Meeting

“…Islets are human micro-organs and should be regulated consistent with the pancreas and other human organs, which are not regulated by the FDA in the US and for which BLAs are not required [4,5] (Figure 1).…”

“…Islets are not drugs, and they are not a form of cellular therapy. Islets, like any other organ for transplantation, encompass the following characteristics [4,5]:…”

“…As a group of experts and leaders in the field of transplantation and endocrinology (Islets for US Collaborative) we strongly advise against the BLA approval and have warned of the negative consequences this would have for patient safety, as well as the field of islet transplantation. We also propose a regulatory path for human islets similar to the one that already exists for other human organs in the US where oversight would be provided by the Health Resources and Services Administration (HRSA) along with the Organ Procurement and Transplantation Network (OPTN) and the United Network for Organ Sharing (UNOS) [5,6]. However, the FDA recently rejected this proposal, and the BLA approval is imminent [7,8].…”

Islet transplantation in the United States – Quo Vadis? An interview with Camilo Ricordi (CR), Ali Naji (AN), Peter Stock (PS), Piotr Witkowski (PW)

“…However, US patients with brittle type 1 diabetes are still unable to undergo this procedure, why is that? CR: Well, the field of allogeneic pancreatic islet cell transplantation is near extinction in the United States, with hardly any islet transplantation procedures currently performed [1]. It has been a heartbreaking situation for me and so frustrating.…”

“…Everywhere else except the United States, islets are regulated as any other organ/tissue for transplantation, which has allowed the field to advance and evolve to help patients worldwide! [1].…”