Translational and Regulatory Challenges of Corneal Endothelial Cell Therapy: A Global Perspective

Cell therapies are emerging as a unique class of clinical therapeutics in medicine. In 2015, Holoclar (ex vivo expanded autologous human corneal epithelial cells containing stem cells) gained the regulatory approval for treating limbal stem cell deficiency after chemical eye burn. This has set a precedent in ophthalmology and in medicine, reinforcing the therapeutic promise of cell therapy. However, to generalize and commercialize cell therapies on a global scale, stringent translational and regulatory requirements need to be fulfilled at both local and international levels. Over the past decade, the Singapore group has taken significant steps in developing human corneal endothelial cell (HCEnC) therapy for treating corneal endothelial diseases, which are currently the leading indication for corneal transplantation in many countries. Successful development of HCEnC therapy may serve as a novel solution to the current global shortage of donor corneas. Based on the experience in Singapore, this review aims to provide a global perspective on the translational and regulatory challenges for bench-to-bedside translation of cell therapy. Specifically, we discussed about the characterization of the critical quality attributes (CQA), the challenges that can affect the CQA, and the variations in the regulatory framework embedded within different regions, including Singapore, Europe, and the United States. Impact statement Functional corneal endothelium is critical to normal vision. Corneal endothelial disease-secondary to trauma, surgery, or pathology-represents an important cause of visual impairment and blindness in both developed and developing countries. Currently, corneal transplantation serves as the current gold standard for treating visually significant corneal endothelial diseases, although limited by the shortage of donor corneas. Over the past decade, human corneal endothelial cell therapy has emerged as a promising treatment option for treating corneal endothelial diseases. To allow widespread application of this therapy, significant regulatory challenges will need to be systematically overcome.