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

Piotr Witkowski; Jon Odorico; Jordan Pyda; Roi Anteby; Robert J Stratta; Beth A Schrope; Mark A Hardy; John Buse; Joseph R Leventhal; Wanxing Cui; Shakir Hussein; Silke Niederhaus; Jason Gaglia; Chirag S Desai; Martin Wijkstrom; Fouad Kandeel; Piotr J Bachul; Yolanda Tai Becker; Ling-Jia Wang; R Paul Robertson; Oyedolamu K Olaitan; Tomasz Kozlowski; Peter L Abrams; Michelle A Josephson; Kenneth A Andreoni; Robert C Harland; Raja Kandaswamy; Andrew M Posselt; Gregory L Szot; Camillo Ricordi; On Behalf Of The Islets For Us Collaborative

doi:10.3390/jcm10132878

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

J Clin Med. 2021 Jun 29;10(13):2878. doi: 10.3390/jcm10132878.

Authors

Piotr Witkowski¹, Jon Odorico², Jordan Pyda³, Roi Anteby^{4

5}, Robert J Stratta⁶, Beth A Schrope⁷, Mark A Hardy⁷, John Buse⁸, Joseph R Leventhal⁹, Wanxing Cui¹⁰, Shakir Hussein¹¹, Silke Niederhaus¹², Jason Gaglia¹³, Chirag S Desai¹⁴, Martin Wijkstrom¹⁵, Fouad Kandeel¹⁶, Piotr J Bachul¹, Yolanda Tai Becker¹, Ling-Jia Wang¹, R Paul Robertson¹⁷, Oyedolamu K Olaitan¹⁸, Tomasz Kozlowski¹⁹, Peter L Abrams²⁰, Michelle A Josephson²¹, Kenneth A Andreoni^{22

23}, Robert C Harland²⁴, Raja Kandaswamy²⁵, Andrew M Posselt²⁶, Gregory L Szot²⁶, Camillo Ricordi²⁷, On Behalf Of The Islets For Us Collaborative

Affiliations

¹ Transplantation Institute, Department of Surgery, University of Chicago, Chicago, IL 60637, USA.
² Division of Transplantation, Department of Surgery, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53792, USA.
³ Beth Israel Deaconess Medical Center, Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
⁴ Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
⁵ Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
⁶ Section of Transplantation, Department of Surgery, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.
⁷ Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
⁸ Division of Endocrinology, Department of Medicine, University of NC, Chapel Hill, NC 27516, USA.
⁹ Department of Surgery, Northwestern University School of Medicine, Chicago, IL 60611, USA.
¹⁰ Cell Therapy Manufacturing Facility, Georgetown University Hospital, Washington, DC 20007, USA.
¹¹ Detroit Medical Center, Department of Surgery, Wayne State School of Medicine, Detroit, MI 48201, USA.
¹² Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
¹³ Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
¹⁴ Department of Surgery, Section of Transplantation, University of NC, Chapel Hill, NC 27516, USA.
¹⁵ Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15260, USA.
¹⁶ Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
¹⁷ Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Washington, Seattle, WA 98133, USA.
¹⁸ Department of Surgery, Rush University Medical Center, Chicago, IL 60612, USA.
¹⁹ Division of Transplantation, Department of Surgery, The University of Oklahoma College of Medicine, Oklahoma City, OK 73104, USA.
²⁰ MedStar Georgetown Transplant Institute, Washington, DC 20007, USA.
²¹ Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
²² Department of Surgery, University of Florida, College of Medicine, Gainesville, FL 32610-0118, USA.
²³ Case Western Reserve University, Cleveland, OH 44106-5047, USA.
²⁴ Department of Surgery, University of Arizona, Tucson, AZ 85711, USA.
²⁵ Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
²⁶ Division of Transplantation, Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA.
²⁷ Diabetes Research Institute and Cell Transplant Center, University of Miami, Miami, FL 33136, USA.

Abstract

The Food and Drug Administration (FDA) has been regulating human islets for allotransplantation as a biologic drug in the US. Consequently, the requirement of a biological license application (BLA) approval before clinical use of islet transplantation as a standard of care procedure has stalled the development of the field for the last 20 years. Herein, we provide our commentary to the multiple FDA's position papers and guidance for industry arguing that BLA requirement has been inappropriately applied to allogeneic islets, which was delivered to the FDA Cellular, Tissue and Gene Therapies Advisory Committee on 15 April 2021. We provided evidence that BLA requirement and drug related regulations are inadequate in reassuring islet product quality and potency as well as patient safety and clinical outcomes. As leaders in the field of transplantation and endocrinology under the "Islets for US Collaborative" designation, we examined the current regulatory status of islet transplantation in the US and identified several anticipated negative consequences of the BLA approval. In our commentary we also offer an alternative pathway for islet transplantation under the regulatory framework for organ transplantation, which would address deficiencies of in current system.

Keywords: Food and Drug Administration; allogenic islet cell transplantation; pancreas.

Grants and funding

P30 DK124723/DK/NIDDK NIH HHS/United States