The Interdisciplinary Stem Cell Institute's Use of Food and Drug Administration-Expanded Access Guidelines to Provide Experimental Cell Therapy to Patients With Rare Serious Diseases.

Darcy L Difede,Krystalenia Valasaki,Risset Silvera,Andrea J Santamaría ,Kimberly Anderson ,Ivonne H Schulman ,Aisha Khan,Barth A Green,Ming Sing ,Michael Bellio ,Dileep R Yavagal,Anil K Lalwani ,James D Guest ,Sunjay Kaushal,Marietsy V Pujol,S Shelby Burks ,Karen Bates ,W Dalton Dietrich,Allan D Levi,Joshua M Hare,Adriana E Brooks ,Bangon Longsomboon

doi:10.3389/fcell.2021.675738

Abstract

The U.S. Food and Drug Administration (FDA) provides guidance for expanded access to experimental therapies, which in turn plays an important role in the Twenty-first Century Cures Act mandate to advance cell-based therapy. In cases of incurable diseases where there is a lack of alternative treatment options, many patients seek access to cell-based therapies for the possibility of treatment responses demonstrated in clinical trials. Here, we describe the use of the FDA’s expanded access to investigational new drug (IND) to address rare and emergency conditions that include stiff-person syndrome, spinal cord injury, traumatic brain stem injury, complex congenital heart disease, ischemic stroke, and peripheral nerve injury. We have administered both allogeneic bone marrow-derived mesenchymal stem cell (MSC) and autologous Schwann cell (SC) therapy to patients upon emergency request using Single Patient Expanded Access (SPEA) INDs approved by the FDA. In this report, we present our experience with 10 completed SPEA protocols.

Highlights

There are many rare and serious pathological disorders that have no definitive or curative therapeutic modalities
Food and Drug Administration (FDA) investigational new drug (IND) # 16093 Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine ISCI Joshua Hare, MD Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine University of Miami Bone marrow derived human Mesenchymal stem cells (MSCs) Single patient expanded access IND to deliver allogeneic mesenchymal stem cells (Allo-hMSCs) to a woman with Stiff Person Syndrome Allo-hMSCs source manufactured by the CRCMP
In the Single Patient Expanded Access (SPEA) INDs reported here, MSCs and Schwann cell (SC) were applied to a range of life-threatening and traumatic injuries

Summary

INTRODUCTION

There are many rare and serious pathological disorders that have no definitive or curative therapeutic modalities. Autologous and allogenic cell-based therapy, with bone marrow-derived mesenchymal stem cells (BMSCs), holds promise as a therapeutic strategy with a pleotropic mechanism of action, an ability to home in sites of inflammation and injury, and a proven safety record (Bagno et al, 2018; Pittenger et al, 2019; Rieger et al, 2019). In these therapies, primary cells are isolated from donor tissue, expanded, analyzed in a current Good Manufacturing Practice (cGMP) laboratory environment, and delivered to patients. We have outlined the regulatory pathway required by the FDA to initiate a SPEA IND for the assessment of novel cell therapies

MATERIALS AND METHODS

RESULTS

Design and investigational plan

DISCUSSION

DATA AVAILABILITY STATEMENT

ETHICS STATEMENT