Navigating Market Authorization: The Path Holoclar Took to Become the First Stem Cell Product Approved in the European Union

• Published in: Stem cells translational medicine 2018-01, Vol.7 (1), p.146-154
• Main Authors: Pellegrini, Graziella, Ardigò, Diego, Milazzo, Giovanni, Iotti, Giorgio, Guatelli, Paolo, Pelosi, Danilo, De Luca, Michele
• Format: Article
• Language: English
• Subjects: Adult Stem Cells; Autografts; Autologous stem cell transplantation; Cell Culture Advances; Cell Delivery Strategies; Cellular therapy; Clinical Application / Translation; Cornea; Epithelial cells; Gene therapy; Good Manufacturing Practice; Growth factors; Limbal Epithelial /Corneal Stem Cells; Manufacturing; Marketing; Patients; Product quality; Regulation; Regulatory approval; Stem cells; Stem/progenitor cell; Technological Advancements; Tissue engineering; Tissue Engineering and Regenerative Medicine; Tissue regeneration; Tissue‐specific stem cells; Translational s and Reviews; Transplants & implants
• ISSN: 2157-6564; 2157-6580
• DOI: 10.1002/sctm.17-0003

Gene therapy, cell therapy, and tissue engineering have the potential to revolutionize the treatment of disease and injury. Attaining marketing authorization for such advanced therapy medicinal products (ATMPs) requires a rigorous scientific evaluation by the European Medicines Agency—authorization is only granted if the product can fulfil stringent requirements for quality, safety, and efficacy. However, many ATMPs are being provided to patients under alternative means, such as “hospital exemption” schemes. Holoclar (ex vivo expanded autologous human corneal epithelial cells containing stem cells), a novel treatment for eye burns, is one of the few ATMPs to have been granted marketing authorization and is the first containing stem cells. This review highlights the differences in standards between an authorized and unauthorized medicinal product, and specifically discusses how the manufacture of Holoclar had to be updated to achieve authorization. The result is that patients will have access to a therapy that is manufactured to high commercial standards, and is supported by robust clinical safety and efficacy data. Stem Cells Translational Medicine 2018;7:146–154 The role of clonogenic keratinocytes in generation and renewal of the corneal epithelium. The holoclone differentiation process from highly proliferative self‐renewing holoclones to transiently amplifying cells (meroclones and paraclones). A confocal microscopy image of holoclone stem cells is on the left showing high expression of ΔNp63α, an isoform of the p63 transcription factor.