Advanced Therapy Medicinal Products for the Eye: Definitions and Regulatory Framework
Abstract
:1. Introduction
2. ATMP Regulatory Framework
2.1. ATMP Regulatory Framework in the EU
2.2. Regulatory Framework for Cell- and Gene-Based Therapies in Other Jurisdictions
3. Definitions and ATMP Classification Criteria
3.1. Cell-Based Medicinal Products: Somatic Cell Therapy and Tissue-Engineered Medicinal Products
Somatic Cell Therapy and Tissue Engineered Medicinal Products for the Eye
3.2. Gene Therapy Medicinal Products
Gene Therapy Medicinal Products for the Eye
3.3. Combined ATMPs
Combined ATMPs for the Eye
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Jurisdiction | European Union | United States | Japan |
---|---|---|---|
Agency | European Medicines Agency (EMA) | Food and Drug Administration (FDA) | Pharmaceuticals and Medical Devices Agency (PMDA) Ministry of Health, Labour and Welfare (MHLW) |
Regulatory framework | Directive 2001/83/EC (related to medical products for human use) European Commission 2007_Regulation EC No. 1394/2007 (related to advanced therapy medicinal products) | Federal Food, Drug, and Cosmetic Act (FDCA) and the Public Health Services Act (PHSA) Regenerative Medicine Advanced Therapy (RMAT) designation: section 3033 of the 21st Century Cures Act. | Act on the Safety of Regenerative Medicine (RM Act) and Pharmaceuticals and Medical Devices Act (PMD Act) 1960 Act No. 145 revised by 2013 Act No. 84 |
Therapy classification | Somatic cell therapy medicinal products (sCTMPs), tissue engineered products (TEPs), gene therapy medicinal products (GTMPs), and combined ATMPs (cATMPs) | Cell therapy and gene therapy products | Gene-, cell-, and tissue-based therapies |
Product (Commercial Name or Number Designated by EMA 1) | sCTMP 2 or TEP 3 | Manufacturer | Active Substance | Administration Route | Indication | Regulatory Status |
---|---|---|---|---|---|---|
EU/3/11/874 | sCTMP, as implanted cells are expected to help retinal function | Astellas Pharma Europe B.V.(Leiden, The Netherlands) | Human embryonic stem-cell-derived retinal pigment epithelial cells | Intravitreal injection | Stargardt’s disease | Orphan medicinal product designation by the EMA in 2011 Orphan medicinal product designation by the FDA 4 for the treatment of Stargardt’s macular dystrophy |
EU/3/13/1168 | TEP, as implanted cells expected to help corneal regeneration | University of Newcastle. (Newcastle upon Tyne, United Kingdom) | Ex Vivo expanded autologous human corneal epithelium containing stem cells | Transplantation of a cell sheet | Limbal stem cell deficiency | Orphan medicinal product designation by the EMA in 2013 |
EU/3/14/1340 | TEP, as implanted cells, expected to help corneal regeneration | NHS National Services Scotland, trading as Scottish National Blood Transfusion Service. (Edinburgh, United Kingdom) | Culture allogeneic corneal limbal stem cells | Transplantation of a cell sheet | Limbal stem cell deficiency | Orphan medicinal product designation by the EMA in 2014 |
OraNera (EMEA/H/C/002443) | TEP, as OraNera, expected to replace damaged corneal cells | CellSeed Europe Ltd.. (London, United Kingdom) | Autologous oral mucosal epithelial cells | Transplantation of a cell sheet | Limbal stem cell deficiency | Application for a marketing authorization withdrawn from the EMA in 2013 |
Holoclar (EU/3/08/579) | TEP (EMA classification) | Holostem Terapie Avanzate S.R.L.(Modena, Italy) | Ex vivo expan ded autologous human corneal epithelium containing stem cells | Transplantation of a cell sheet | Moderate-severe limbal stem cell deficiency, unilateral or bilateral, due to chemical or physical burns | Orphan medicinal product designation by the EMA in 2008 Conditional marketing authorization by the EMA in 2015. The orphan medicinal product designation was maintained |
Nepic | Human somatic stem cell-processed products (Japanese PMDA 5 classification) | Japan Tissue Engineering Co., Ltd. (Gamagori, Japan) | Human autologous corneal limbus-derived corneal epithelial cell sheet | Transplantation of a cell sheet | Limbal stem cell deficiency | Orphan regenerative medical product designation by the Japanese PMDA in 2020 |
Product (Commercial Name or Number Designated by EMA 1) | Manufacturer | Active Substance | Administration Route | Indication | REGULATORY STATUS |
---|---|---|---|---|---|
Vitravene EMA/H/C/000244 | Novartis (Basel, Switzerland) | Fomivirsen (antisense PODN 2) | Intravitreal injection | CMV 3 retinitis in HIV 4 infection | Marketing authorization by the FDA 5 1998 and by the EMA 1999. Withdrawn in 2002 in the EU 6 and in 2006 in the US 7 Currently authorized in Switzerland |
Macugen EMA/671614/2010 | Pfizer (New York, USA) | Pegaptanib (RNA aptamer) | Intravitreal injection | Wet form of AMD 8/Diabetic macular edema | Marketing authorization by the EMA and by the FDA in 2006/ Withdrawn in 2011 to include a new application (diabetic macular edema) |
Luxturna EU/3/15/1518; EU/3/12/981 | Novartis | Voretigene neparvovec (AAV 9-RPE65) | Subretinal injection | Retinitis pigmentosa/Leber´s congenital amaurosis | Marketing authorization by the EMA in 2018 and by the FDA in 2017 |
Product (Commercial Name or Number Designated by EMA 1) | Manufacturer | Active Substance | Administration Route | Indication | Regulatory Status |
---|---|---|---|---|---|
NT-501 (EMA/COMP/808529/2012) (EMA/COMP/682942/2012) | Neurotech Pharmaceuticals Inc. (Cumberland, RI, USA) / Enpharma Ltd. (Oxford, United Kingdom) | Encapsulated human retinal pigment epithelial cell line transfected with plasmid vector expressing human CNTF 3 | Intravitreal implant | Retinitis pigmentosa/Macular telangiectasia type 2 | Orphan designation by the FDA 2 in 2004 and by the EMA in 2013/Orphan designation by the EMA and the FDA in 2012 |
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López-Paniagua, M.; de la Mata, A.; Galindo, S.; Blázquez, F.; Calonge, M.; Nieto-Miguel, T. Advanced Therapy Medicinal Products for the Eye: Definitions and Regulatory Framework. Pharmaceutics 2021, 13, 347. https://doi.org/10.3390/pharmaceutics13030347
López-Paniagua M, de la Mata A, Galindo S, Blázquez F, Calonge M, Nieto-Miguel T. Advanced Therapy Medicinal Products for the Eye: Definitions and Regulatory Framework. Pharmaceutics. 2021; 13(3):347. https://doi.org/10.3390/pharmaceutics13030347
Chicago/Turabian StyleLópez-Paniagua, Marina, Ana de la Mata, Sara Galindo, Francisco Blázquez, Margarita Calonge, and Teresa Nieto-Miguel. 2021. "Advanced Therapy Medicinal Products for the Eye: Definitions and Regulatory Framework" Pharmaceutics 13, no. 3: 347. https://doi.org/10.3390/pharmaceutics13030347
APA StyleLópez-Paniagua, M., de la Mata, A., Galindo, S., Blázquez, F., Calonge, M., & Nieto-Miguel, T. (2021). Advanced Therapy Medicinal Products for the Eye: Definitions and Regulatory Framework. Pharmaceutics, 13(3), 347. https://doi.org/10.3390/pharmaceutics13030347