Terapias avanzadas

• Incluye un principio activo que contiene un ácido nucleico recombinante, o está constituido por él, utilizado en seres humanos, o administrado a los mismos, con objeto de regular, reparar, sustituir, añadir o eliminar una secuencia génica.
• El efecto terapéutico, profiláctico o diagnóstico depende directamente de la secuencia del ácido nucleico recombinante que contenga, o del producto de la expresión genética de dicha secuencia.

• Contiene células o tejidos, o está constituido por ellos, que han sido objeto de manipulación sustancial de modo que se hayan alterado sus características biológicas, funciones fisiológicas o propiedades estructurales pertinentes para el uso clínico previsto, o por células o tejidos que no se pretende destinar a la misma función esencial en el receptor y en el donante.
• Se presenta con propiedades para ser usado por seres humanos, o administrado a los mismos, con objeto de tratar, prevenir o diagnosticar una enfermedad mediante la acción farmacológica, inmunológica o metabólica de sus células o tejidos.

Por “producto de ingeniería tisular” se entenderá aquel que contiene o está formado por células o tejidos manipulados por ingeniería y del que se alega que tiene propiedades, se emplea o se administra a las personas para regenerar, restaurar o reemplazar un tejido humano.

Las células o tejidos se considerarán “manipulados por ingeniería” si cumplen al menos una de las condiciones siguientes:

• Las células o tejidos han sido sometidos a manipulación sustancial, de modo que se logren las características biológicas, funciones fisiológicas o propiedades estructurales pertinentes para la regeneración, reparación o sustitución pretendidas.
• Las células o tejidos no están destinados a emplearse para la misma función o funciones esenciales en el receptor y en el donante.

• Tiene que incorporar, como parte integrante del mismo, uno o más productos sanitarios en el sentido del artículo 1, apartado 2, letra a), de la Directiva 93/42/CEE, o uno o más productos sanitarios implantables activos en el sentido del artículo 1, apartado 2, letra c), de la Directiva 90/385/CEE.
• La parte celular o tisular tiene que contener células o tejidos viables.
• La parte celular o tisular que contenga células o tejidos no viables tiene que poder ejercer en el organismo humano una acción que pueda considerarse fundamental respecto de la de los productos sanitarios mencionados.

2025

• Hidalgo-Simon, A., Pothet, C., Cooke, E., & Thirstrup, S. (2025). Academic development of advanced therapies-How to foster their future in the clinic. British journal of clinical pharmacology, 91(4), 1080–1083. https://doi.org/10.1002/bcp.70024

• Olaghere, J., Williams, D. A., Farrar, J., Büning, H., Calhoun, C., Ho, T., Inamdar, M. S., Liu, D., Makani, J., Nyarko, K., Ruiz, S., Tisdale, J., McCune, J. M., Boadi, E., & Reagan-Udall Foundation For The FDA (2025). Scientific Advancements in Gene Therapies: Opportunities for Global Regulatory Convergence. Biomedicines, 13(3), 758. https://doi.org/10.3390/biomedicines13030758

• Palomo, G. M., Pose-Boirazian, T., Naumann-Winter, F., Costa, E., Duarte, D. M., Kalland, M. E., Malikova, E., Matusevicius, D., Vitezic, D., Larsson, K., Magrelli, A., Stoyanova-Beninska, V., & Mariz, S. (2025). Navigating the orphan medicinal product designation: Evidence requirements for gene therapies in Europe. Molecular therapy: the journal of the American Society of Gene Therapy, 33(6), 2834–2841. https://doi.org/10.1016/j.ymthe.2024.10.015

• Rodríguez, L., de Felipe, P., Martín, R., Martínez, J., Ordóñez, D., Rojo, S., Martínez, J. F., Rincón, E., Cejalvo, T., Izquierdo, I., Montanuy, I., & Timón, M. (2025). The Coming of Age of Gene Therapy for the Treatment of Human Diseases: A Regulatory Perspective. Human gene therapy, 36(17-18), 1103–1117. https://doi.org/10.1177/10430342251372047

2024

• Celis, P., Farinelli, G., Hidalgo-Simon, A., Meij, P., Tihaya, M., Schüssler-Lenz, M., & Timón, M. (2024). EMA commentary on the guideline on quality, nonclinical and clinical aspects of medicinal products containing genetically modified cells. British journal of clinical pharmacology, 90(5), 1203–1212. https://doi.org/10.1111/bcp.16047

• Kalland, M. E., Pose-Boirazian, T., Palomo, G. M., Naumann-Winter, F., Costa, E., Matusevicius, D., Duarte, D. M., Malikova, E., Vitezic, D., Larsson, K., Magrelli, A., Stoyanova-Beninska, V., & Mariz, S. (2024). Advancing rare disease treatment: EMA’s decade-long insights into engineered adoptive cell therapy for rare cancers and orphan designation. Gene therapy, 31(7-8), 366–377. https://doi.org/10.1038/s41434-024-00446-0

• Olesti, E., Nuevo, Y., Bachiller, M., Guillen, E., Bascuas, J., Varea, S., Saez-Peñataro, J., & Calvo, G. (2024). Academic challenges on advanced therapy medicinal products’ development: a regulatory perspective. Cytotherapy, 26(3), 221–230. https://doi.org/10.1016/j.jcyt.2023.12.005

• Tavridou, A., Rogers, D., Farinelli, G., Gravanis, I., & Jekerle, V. (2024). Genome-editing medicinal products: the EMA perspective. Nature reviews. Drug discovery, 23(4), 242–243. https://doi.org/10.1038/d41573-024-00050-2

2023

• Estévez Álamo, J., Timón, M., Sánchez Afán de Rivera, I., Iriarte Torres, B., & Serrano Castro, M. A. (2023). Clinical Trials on Advanced Therapy Investigational Medicinal Products in Spain (2004-2022): Experience and Challenges for the Future. Advances in experimental medicine and biology, 1430, 23–39. https://doi.org/10.1007/978-3-031-34567-8_2

• Palomo, G. M., Pose-Boirazian, T., Naumann-Winter, F., Costa, E., Duarte, D. M., Kalland, M. E., Malikova, E., Matusevicius, D., Vitezic, D., Larsson, K., Magrelli, A., Stoyanova-Beninska, V., & Mariz, S. (2023). The European landscape for gene therapies in orphan diseases: 6-year experience with the EMA Committee for Orphan Medicinal Products. Molecular therapy : the journal of the American Society of Gene Therapy, 31(12), 3414–3423. https://doi.org/10.1016/j.ymthe.2023.09.020

• Salmikangas, P., Carlsson, B., Klumb, C., Reimer, T., & Thirstrup, S. (2023). Potency testing of cell and gene therapy products. Frontiers in medicine, 10, 1190016. https://doi.org/10.3389/fmed.2023.1190016

• Schuessler-Lenz, M., Herberts, C., Reischl, I., Ruiz, S., Celis, P., Beuneu, C., Kjeken, R., & Timón, M. (2023). Marketing Regulatory Oversight of Advanced Therapy Medicinal Products in Europe. Advances in experimental medicine and biology, 1430, 1–21. https://doi.org/10.1007/978-3-031-34567-8_1

2022

• Hines, P. A., Agricola, E., Llinares Garcia, J., O’Dwyer, L., & Herold, R. (2022). Therapeutic genome editing: regulatory horizons. Nature reviews. Drug discovery, 21(1), 1–2. https://doi.org/10.1038/d41573-021-00130-7

• Pearson, A. D., Rossig, C., Mackall, C., Shah, N. N., Baruchel, A., Reaman, G., Ricafort, R., Heenen, D., Bassan, A., Berntgen, M., Bird, N., Bleickardt, E., Bouchkouj, N., Bross, P., Brownstein, C., Cohen, S. B., de Rojas, T., Ehrlich, L., Fox, E., Gottschalk, S., … Vassal, G. (2022). Paediatric Strategy Forum for medicinal product development of chimeric antigen receptor T-cells in children and adolescents with cancer: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration. European journal of cancer (Oxford, England: 1990), 160, 112–133. https://doi.org/10.1016/j.ejca.2021.10.016

2021

• Aledo-Serrano, A., Gil-Nagel, A., Isla, J., Mingorance, A., Mendez-Hermida, F., & Hernandez-Alcoceba, R. (2021). Gene therapies and COVID-19 vaccines: a necessary discussion in relation with viral vector-based approaches. Orphanet journal of rare diseases, 16(1), 316. https://doi.org/10.1186/s13023-021-01958-3

• Tavridou, A., Rogers, D., Bonelli, M., Schiel, A., & Hidalgo-Simon, A. (2021). Towards a better use of scientific advice for developers of advanced therapies. British journal of clinical pharmacology, 87(6), 2459–2464. https://doi.org/10.1111/bcp.14672

2020

• Lamas-Díaz, M. J., & Hernández-García, C. (2020). Advanced therapies. Terapias avanzadas. Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria, 44(1), 1–2. https://doi.org/10.7399/fh.11373

2019

• Barkholt, L., Voltz-Girolt, C., Raine, J., Salmonson, T., & Schüssler-Lenz, M. (2019). Regulatory watch: European regulatory experience with advanced therapy medicinal products. Nature reviews. Drug discovery, 18(1), 8–9. https://doi.org/10.1038/nrd.2018.200

• Whomsley, R., Brendler-Schwaab, S., Griffin, E., Jensen, J., Moermond, C., Scholz, B., Nilssen, L. S., Stemplewski, H., & Roennefahrt, I. (2019). Commentary on the draft revised guideline on the environmental risk assessment of medicinal products for human use. Environmental Sciences Europe, 31(1). https://doi.org/10.1186/s12302-019-0198-9

2017

• Boráň, T., Menezes-Ferreira, M., Reischl, I., Celis, P., Ferry, N., Gänsbacher, B., Krafft, H., Lipucci di Paola, M., Sladowski, D., & Salmikangas, P. (2017). Clinical Development and Commercialization of Advanced Therapy Medicinal Products in the European Union: How Are the Product Pipeline and Regulatory Framework Evolving? Human gene therapy. Clinical development, 28(3), 126–135. https://doi.org/10.1089/humc.2016.193

2016

• Ziogas C. (2016). A regulator’s insights for SMEs in the biologics and advanced therapies sectors. Regulatory Rapporteur, 13(2), 23–25.

2015

• Celis, P., Ferry, N., Hystad, M., Schüßler-Lenz, M., Doevendans, P. A., Flory, E., Beuneu, C., Reischl, I., & Salmikangas, P. (2015). Advanced Therapy Medicinal Products: How to Bring Cell-Based Medicinal Products Successfully to the Market – Report from the CAT-DGTI-GSCN Workshop at the DGTI Annual Meeting 2014. Transfusion medicine and hemotherapy: offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie, 42(3), 194–199. https://doi.org/10.1159/000382107

• Flory, E., Gasparini, P., Jekerle, V., Palomäki, T., Celis, P., Boráň, T., Mcblane, J. W., Borg, J. J., Kyselovic, J., Lipnik-stangelj, M., Maimets, T., Menezes-Ferreira, M., Pante, G., Prilla, S., Riekstina, U., Schneider, C. K., Tsiftsoglou, A., & Salmikangas, P. (2015). Regulatory viewpoints on the development of advanced stem cell–based medicinal products in light of the first EU-approved stem cell product. Cell and Gene Therapy Insights, 1(1), 109–127. https://doi.org/10.18609/cgti.2015.010

• Salmikangas, P., Menezes-Ferreira, M., Reischl, I., Tsiftsoglou, A., Kyselovic, J., Borg, J. J., Ruiz, S., Flory, E., Trouvin, J. H., Celis, P., Ancans, J., Timon, M., Pante, G., Sladowski, D., Lipnik-Stangelj, M., & Schneider, C. K. (2015). Manufacturing, characterization and control of cell-based medicinal products: challenging paradigms toward commercial use. Regenerative medicine, 10(1), 65–78. https://doi.org/10.2217/rme.14.65

• Salmikangas, P., Schuessler-Lenz, M., Ruiz, S., Celis, P., Reischl, I., Menezes-Ferreira, M., Flory, E., Renner, M., & Ferry, N. (2015). Marketing Regulatory Oversight of Advanced Therapy Medicinal Products (ATMPs) in Europe: The EMA/CAT Perspective. Advances in experimental medicine and biology, 871, 103–130. https://doi.org/10.1007/978-3-319-18618-4_6

2014

• Caneva, L., Bonelli, M., Papaluca-Amati, M., & Vidal, J. M. (2014). Critical review on the Environmental Risk Assessment of medicinal products for human use in the centralised procedure. Regulatory toxicology and pharmacology: RTP, 68(3), 312–316. https://doi.org/10.1016/j.yrtph.2014.01.002

• Narayanan, G., Cossu, G., Galli, M. C., Flory, E., Ovelgonne, H., Salmikangas, P., Schneider, C. K., & Trouvin, J. H. (2014). Clinical development of gene therapy needs a tailored approach: a regulatory perspective from the European Union. Human gene therapy. Clinical development, 25(1), 1–6. https://doi.org/10.1089/humc.2013.230

2013

• Aiuti, A., Cossu, G., de Felipe, P., Galli, M. C., Narayanan, G., Renner, M., Stahlbom, A., Schneider, C. K., & Voltz-Girolt, C. (2013). The committee for advanced therapies’ of the European Medicines Agency reflection paper on management of clinical risks deriving from insertional mutagenesis. Human gene therapy. Clinical development, 24(2), 47–54. https://doi.org/10.1089/humc.2013.119

• Barkholt, L., Flory, E., Jekerle, V., Lucas-Samuel, S., Ahnert, P., Bisset, L., Büscher, D., Fibbe, W., Foussat, A., Kwa, M., Lantz, O., Mačiulaitis, R., Palomäki, T., Schneider, C. K., Sensebé, L., Tachdjian, G., Tarte, K., Tosca, L., & Salmikangas, P. (2013). Risk of tumorigenicity in mesenchymal stromal cell-based therapies–bridging scientific observations and regulatory viewpoints. Cytotherapy, 15(7), 753–759. https://doi.org/10.1016/j.jcyt.2013.03.005

• Melchiorri, D., Pani, L., Gasparini, P., Cossu, G., Ancans, J., Borg, J. J., Drai, C., Fiedor, P., Flory, E., Hudson, I., Leufkens, H. G., Müller-Berghaus, J., Narayanan, G., Neugebauer, B., Pokrotnieks, J., Robert, J. L., Salmonson, T., & Schneider, C. K. (2013). Regulatory evaluation of Glybera in Europe – two committees, one mission. Nature reviews. Drug discovery, 12(9), 719. https://doi.org/10.1038/nrd3835-c1

• Vestergaard, H. T., D’Apote, L., Schneider, C. K., & Herberts, C. (2013). The evolution of nonclinical regulatory science: advanced therapy medicinal products as a paradigm. Molecular therapy : the journal of the American Society of Gene Therapy, 21(9), 1644–1648. https://doi.org/10.1038/mt.2013.175

2012

• Galli M. C. (2012). Long-term follow-up of cancer patients treated with gene therapy medicinal products. The journal of gene medicine, 14(6), 440–442. https://doi.org/10.1002/jgm.2638

• Klug, B., Celis, P., Carr, M., & Reinhardt, J. (2012). Regulatory structures for gene therapy medicinal products in the European Union. Methods in enzymology, 507, 337–354. https://doi.org/10.1016/B978-0-12-386509-0.00017-X

• Maciulaitis, R., D’Apote, L., Buchanan, A., Pioppo, L., & Schneider, C. K. (2012). Clinical development of advanced therapy medicinal products in Europe: evidence that regulators must be proactive. Molecular therapy: the journal of the American Society of Gene Therapy, 20(3), 479–482. https://doi.org/10.1038/mt.2012.13

2011

• Salmikangas, P., & Celis, P. (2011). Current challenges in the development of novel cell-based medicinal products. Regulatory Rapporteur, 8(7-8), 4–7. Vamvakas S., Martinalbo J., Pita R. & Isaac M. (2011). On the edge of new technologies (advanced therapies, nanomedicines). Drug discovery today. Technologies, 8(1), e1–e42. https://doi.org/10.1016/j.ddtec.2011.04.001

• Voltz-Girolt, C., Celis, P., Boucaumont, M., D’Apote, L., Pinheiro, M. H., & Papaluca-Amati, M. (2011). The advanced therapy classification procedure. Overview of experience gained so far. Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz, 54(7), 811–815. https://doi.org/10.1007/s00103-011-1309-y

2010

• Committee for Advanced Therapies (CAT), CAT Scientific Secretariat, Schneider, C. K., Salmikangas, P., Jilma, B., Flamion, B., Todorova, L. R., Paphitou, A., Haunerova, I., Maimets, T., Trouvin, J. H., Flory, E., Tsiftsoglou, A., Sarkadi, B., Gudmundsson, K., O’Donovan, M., Migliaccio, G., Ancāns, J., Maciulaitis, R., Robert, J. L., … Celis, P. (2010). Challenges with advanced therapy medicinal products and how to meet them. Nature reviews. Drug discovery, 9(3), 195–201. https://doi.org/10.1038/nrd3052

• Committee for Advanced Therapies and CAT Scientific Secretariat (2010). Use of unregulated stem-cell based medicinal products. Lancet (London, England), 376(9740), 514. https://doi.org/10.1016/S0140-6736(10)61249-4

• Jekerle, V., Schröder, C., & Pedone, E. (2010). Legal basis of the Advanced Therapies Regulation. Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz, 53(1), 4–8. https://doi.org/10.1007/s00103-009-0990-6

2009

• Celis, P., Miglicacio, G., Pedone, E., Petracek, J., Pinheiro, M. H., Salmikangas, P., & Schneider, C. K. (2009). Advanced therapies: Regulatory principles and practice. Regulatory Rapporteur, 6, 12–16.

• Celis, P., & Pedone, E. (2009). The Committee for Advanced Therapies at the European Medicines Agency and the advanced therapies certification procedure. Drug Development, 4, 64–67.