This article describes the regulatory pathway that enabled the translation of academic research and clinical experience of an ex-vivo expanded autologous stem cell-based treatment for limbal stem cell deficiency (LSCD) into a pharmaceutical product compliant with the European Union regulations of Advanced Therapy Medicinal Products (ATMP). Holoclar® was originally developed in Italy as a surgical procedure and used in more than 200 patients. Following the establishment of the EU ATMP Regulation EC 1394/2007, Holoclar development required that manufacturing was as per current Good Manufacturing Practice requirements and collection of retrospective clinical data was ICH-E6 and E3 compliant. Holoclar is an ex-vivo expanded autologous human corneal epithelial cells containing stem cells and is classified as “tissue engineered product”. Based on the evidence of quality and control of the manufacturing process, safety, efficacy and on a positive benefit–risk balance in 104 patients (72.1%) of 148 patients treated, Holoclar received conditional Marketing Approval in the EU. Holoclar is the first medicine approved in the EU for this rare eye condition that can result in blindness.
Holoclar: first of its kind in more ways than one / Milazzo, G; Ardigò, D; Toschi, M; Matuska, S; Rama, P; DE LUCA, Michele; Pellegrini, Graziella. - In: CELL & GENE THERAPY INSIGHTS. - ISSN 2059-7800. - 2(2):(2016), pp. 183-197. [10.18609/cgti.2016.023]