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Palomo GM, Pose-Boirazian T, Naumann-Winter F, Costa E, Duarte DM, Kalland ME, Malikova E, Matusevicius D, Vitezic D, Larsson K, Magrelli A, Stoyanova-Beninska V, Mariz S. Navigating the orphan medicinal product designation: Evidence requirements for gene therapies in Europe. Mol Ther 2024:S1525-0016(24)00675-0. [PMID: 39489919 DOI: 10.1016/j.ymthe.2024.10.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 09/25/2024] [Accepted: 10/23/2024] [Indexed: 11/05/2024] Open
Abstract
To provide insight into regulatory decision-making at the time of granting initial orphan designation by the Committee for Orphan Medicinal Products, we have conducted a retrospective analysis for viral vector-mediated gene therapies in rare non-oncological conditions with respect to the data provided to support the criteria to be met in successful applications. We found that a high proportion of non-clinical in vivo data was used for gene therapies, indicating earlier submissions of products that are at the stage of preclinical research and not in clinical development. Clinical data were submitted in only 13% of the applications, containing preliminary results derived from early-stage clinical trials in few patients. Mouse models were used in the majority of the submissions to generate meaningful non-clinical in vivo data highlighting their utility for proof-of-concept studies, and half of the applications containing non-clinical data generated results based solely on surrogate endpoints. The criterion of significant benefit was applicable in 54% of the submissions, which indicates that sponsors are focusing gene therapy development in areas of high unmet medical need, particularly where there are no authorized medicines available.
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Affiliation(s)
- Gloria M Palomo
- Agencia Española de Medicamentos y Productos Sanitarios, Calle Campezo 1 Edificio 8, 28022 Madrid, Spain; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS, Amsterdam, the Netherlands.
| | - Tomas Pose-Boirazian
- Orphan Medicines Office, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands
| | - Frauke Naumann-Winter
- Bundesinstitut für Arzneimittel und Medizinprodukte, Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS, Amsterdam, the Netherlands
| | - Enrico Costa
- Agenzia Italiana del Farmaco, Via del Tritone 181, 00187 Rome, Italy; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS, Amsterdam, the Netherlands
| | - Dinah M Duarte
- INFARMED - National Authority of Medicines and Health Products, I.P., 1749-004 Lisbon, Portugal; Universidade de Lisboa, Faculdade de Farmácia, 1649-003 Lisbon, Portugal; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS, Amsterdam, the Netherlands
| | - Maria E Kalland
- Norwegian Medical Products Agency, Grensesvingen 26, 0663 Oslo, Norway; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS, Amsterdam, the Netherlands
| | - Eva Malikova
- Department of Pharmacology and Toxicology, Comenius University, 832 32 Bratislava, Slovakia; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS, Amsterdam, the Netherlands
| | - Darius Matusevicius
- Läkemedelsverket, Dag Hammarskjölds väg 42, 75237 Uppsala, Sweden; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS, Amsterdam, the Netherlands
| | - Dinko Vitezic
- Rijeka University School of Medicine and University Hospital Centre Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS, Amsterdam, the Netherlands
| | - Kristina Larsson
- Orphan Medicines Office, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands
| | - Armando Magrelli
- National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS, Amsterdam, the Netherlands
| | - Violeta Stoyanova-Beninska
- Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS, Amsterdam, the Netherlands
| | - Segundo Mariz
- Orphan Medicines Office, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands.
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Fürst-Ladani S, Bührer A, Fürst W, Schober-Ladani N. Regulatory Aspects for Approval of Advanced Therapy Medicinal Products in the EU. Handb Exp Pharmacol 2024; 284:367-387. [PMID: 37017789 DOI: 10.1007/164_2023_648] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2023]
Abstract
In the European Union (EU), advanced therapy medicinal products (ATMPs) undergo evaluation by the European Medicines Agency's (EMA) Committee for Advanced Therapies (CAT) to obtain marketing authorization under the centralized procedure. Because of the diversity and complexity of ATMPs, a tailored approach to the regulatory process is required that needs to ensure the safety and efficacy of each product. Since ATMPs often target serious diseases with unmet medical need, the industry and authorities are interested in providing treatment to patients in a timely manner through optimized and expedited regulatory pathways. EU legislators and regulators have implemented various instruments to support the development and authorization of innovative medicines by offering scientific guidance at early stages, incentives for small developers and products for rare diseases, accelerated evaluation of marketing authorization applications, different types of marketing authorizations, and tailored programs for medicinal products with the orphan drug designation (ODD) and the Priority Medicines (PRIME) scheme. Since the regulatory framework for ATMPs was established, 20 products have been licenced, 15 with orphan drug designation, and 7 supported by PRIME. This chapter discusses the specific regulatory framework for ATMPs in the EU and highlights previous successes and remaining challenges.
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Affiliation(s)
| | - Anja Bührer
- SFL Regulatory Affairs and Scientific Communication GmbH, Basel, Switzerland
| | - Walter Fürst
- SFL Regulatory Affairs and Scientific Communication GmbH, Basel, Switzerland
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3
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Palomo GM, Pose-Boirazian T, Naumann-Winter F, Costa E, Duarte DM, Kalland ME, Malikova E, Matusevicius D, Vitezic D, Larsson K, Magrelli A, Stoyanova-Beninska V, Mariz S. The European landscape for gene therapies in orphan diseases: 6-year experience with the EMA Committee for Orphan Medicinal Products. Mol Ther 2023; 31:3414-3423. [PMID: 37794679 PMCID: PMC10727954 DOI: 10.1016/j.ymthe.2023.09.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 08/04/2023] [Accepted: 09/29/2023] [Indexed: 10/06/2023] Open
Abstract
In 2000, the European Union (EU) introduced the orphan pharmaceutical legislation to incentivize the development of medicinal products for rare diseases. The Committee for Orphan Medicinal Products (COMP), the European Medicines Agency committee responsible for evaluation of applications for orphan designation (OD), received an increasing flow of applications in the field of gene therapies over the last years. Here, the COMP has conducted a descriptive analysis of applications regarding gene therapies in non-oncological rare diseases, with respect to (a) targeted conditions and their rarity, (b) characteristics of the gene therapy products proposed for OD, with a focus on the type of vector used, and (c) regulatory aspects pertaining to the type of sponsor and development, by examining the use of available frameworks offered in the EU such as protocol assistance and PRIME. It was noted that gene therapies are being developed by sponsors from different backgrounds. Most conditions being targeted are monogenic, the most common being lysosomal disorders, and with a very low prevalence. Generally, adeno-associated viral vectors were being used to deliver the transgene. Finally, sponsors are not frequently using the incentives that may support the development and the reasons for this are unclear.
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Affiliation(s)
- Gloria M Palomo
- Agencia Española de Medicamentos y Productos Sanitarios, Calle Campezo 1 Edificio 8, 28022 Madrid, Spain; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands.
| | - Tomas Pose-Boirazian
- Orphan Medicines Office, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands
| | - Frauke Naumann-Winter
- Bundesinstitut für Arzneimittel und Medizinprodukte, Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands
| | - Enrico Costa
- Agenzia Italiana del Farmaco, Via del Tritone 181, 00187 Rome, Italy; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands
| | - Dinah M Duarte
- INFARMED - National Authority of Medicines and Health Products, I.P., Avenida do Brasil 53, 1749-004 Lisbon, Portugal; Universidade de Lisboa, Faculdade de Farmácia, Avenida Professor Gama Pinto, 1649-003 Lisbon, Portugal; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands
| | - Maria E Kalland
- Statens Legemiddelverk/The Norwegian Medicines Agency, Grensesvingen 26, 0663 Oslo, Norway; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands
| | - Eva Malikova
- State Institute for Drug Control, Kvetná 11, 825 08 Bratislava, Slovakia; Department of Pharmacology and Toxicology, Comenius University, Odbojárov 10, 832 32 Bratislava, Slovakia; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands
| | - Darius Matusevicius
- Läkemedelsverket, Dag Hammarskjölds väg 42, 75237 Uppsala, Sweden; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands
| | - Dinko Vitezic
- Rijeka University School of Medicine and University Hospital Centre Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands
| | - Kristina Larsson
- Orphan Medicines Office, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands
| | - Armando Magrelli
- National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands
| | - Violeta Stoyanova-Beninska
- College ter Beoordeling van Geneesmiddelen, Graadt van Roggenweg 500, 3531 AH Utrecht, the Netherlands; Committee for Orphan Medicinal Products, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands
| | - Segundo Mariz
- Orphan Medicines Office, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, the Netherlands.
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Piemonti L, Scholz H, de Jongh D, Kerr-Conte J, van Apeldoorn A, Shaw JAM, Engelse MA, Bunnik E, Mühlemann M, Pal-Kutas K, Scott WE, Magalon J, Kugelmeier P, Berishvili E. The Relevance of Advanced Therapy Medicinal Products in the Field of Transplantation and the Need for Academic Research Access: Overcoming Bottlenecks and Claiming a New Time. Transpl Int 2023; 36:11633. [PMID: 37822447 PMCID: PMC10563816 DOI: 10.3389/ti.2023.11633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 09/12/2023] [Indexed: 10/13/2023]
Abstract
The field of transplantation has witnessed the emergence of Advanced Therapy Medicinal Products (ATMPs) as highly promising solutions to address the challenges associated with organ and tissue transplantation. ATMPs encompass gene therapy, cell therapy, and tissue-engineered products, hold immense potential for breakthroughs in overcoming the obstacles of rejection and the limited availability of donor organs. However, the development and academic research access to ATMPs face significant bottlenecks that hinder progress. This opinion paper emphasizes the importance of addressing bottlenecks in the development and academic research access to ATMPs by implementing several key strategies. These include the establishment of streamlined regulatory processes, securing increased funding for ATMP research, fostering collaborations and partnerships, setting up centralized ATMP facilities, and actively engaging with patient groups. Advocacy at the policy level is essential to provide support for the development and accessibility of ATMPs, thereby driving advancements in transplantation and enhancing patient outcomes. By adopting these strategies, the field of transplantation can pave the way for the introduction of innovative and efficacious ATMP therapies, while simultaneously fostering a nurturing environment for academic research.
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Affiliation(s)
- Lorenzo Piemonti
- Diabetes Research Institute, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Hanne Scholz
- Department of Transplant Medicine and Institute for Surgical Research, Oslo University Hospital, Oslo, Norway
| | - Dide de Jongh
- Department of Medical Ethics, Philosophy and History of Medicine, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands
- Department of Nephrology and Transplantation, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands
| | - Julie Kerr-Conte
- Université de Lille, INSERM, Campus Hospitalo-Universitaire de Lille, Institut Pasteur de Lille, U1190-EGID, Lille, France
| | - Aart van Apeldoorn
- Department CBITE, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands
| | - James A. M. Shaw
- Translational and Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom
| | | | - Eline Bunnik
- Department of Medical Ethics, Philosophy and History of Medicine, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands
| | | | | | - William E. Scott
- Translational and Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Jérémy Magalon
- Laboratoire de Culture et Thérapie Cellulaire, Assistance Publique des Hôpitaux de Marseille, Marseille, France
- Vascular Research Center Marseille, INSERM UMRS 1076, Faculté de Pharmacie, Marseille, France
| | | | - Ekaterine Berishvili
- Laboratory of Tissue Engineering and Organ Regeneration, Department of Surgery, University of Geneva, Geneva, Switzerland
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Burns JS. The Evolving Landscape of Potency Assays. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1420:165-189. [PMID: 37258790 DOI: 10.1007/978-3-031-30040-0_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
There is a "goldilocks" aspect to potency assays. On the one hand, a comprehensive evaluation of the cell product with detailed quantitative measurement of the critical quality attribute/s of the desired biological activity is required. On the other hand, the potency assay benefits from simplification and lean approaches that avoid unnecessary complication and enhance robustness, to provide a reproducible and scalable product. There is a need to balance insightful knowledge of complex biological healing processes with straightforward manufacture of an advanced therapeutic medicinal product (ATMP) that can be administered in a trustworthy cost-effective manner. While earlier chapters within this book have highlighted numerous challenges facing the potency assay conundrum, this chapter offers a forward-looking perspective regarding the many recent advances concerning acellular products, cryopreservation, induced MSC, cell priming, nanotechnology, 3D culture, regulatory guidelines and evolving institutional roles, that are likely to facilitate potency assay development in the future.
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Affiliation(s)
- Jorge S Burns
- Department of Environmental and Prevention Sciences, University of Ferrara, Ferrara, Italy.
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Arabi F, Mansouri V, Ahmadbeigi N. Gene therapy clinical trials, where do we go? An overview. Biomed Pharmacother 2022; 153:113324. [PMID: 35779421 DOI: 10.1016/j.biopha.2022.113324] [Citation(s) in RCA: 93] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 06/14/2022] [Accepted: 06/20/2022] [Indexed: 12/18/2022] Open
Abstract
There have been many ups and downs since the introduction of gene therapy as a therapeutic modality for diseases. However, the journey of gene therapy has reached a fundamental milestone, as evidenced by the increasing number of gene therapy products on the market. Looking at the currently approved and under-approval products, as well as the numerous clinical trials in this field, gene therapy has a promising future. Trend of changes in gene therapy strategies, vectors, and targets could be insightful for pharmaceutical companies, policymakers, and researchers. In this paper, following a brief history of gene therapy, we reviewed current gene therapy products as well as gene therapies that may be approved in the near future. We also looked at ten-year changes in gene therapy clinical trials strategies, such as the use of vectors, target cells, transferred genes, and ex-vivo/in-vivo methods, as well as the major fields that gene therapy has entered. Although gene therapy was initially used to treat genetic diseases, cancer now has the greatest number of gene therapy clinical trials. Changes in gene therapy strategies, particularly in pioneering countries in this field, may point to the direction of future clinical products.
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Affiliation(s)
- Fatemeh Arabi
- Gene Therapy Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 1411713135, Iran
| | - Vahid Mansouri
- Gene Therapy Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 1411713135, Iran
| | - Naser Ahmadbeigi
- Gene Therapy Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 1411713135, Iran.
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Ziegler A. [Precision medicine in pediatric neurology exemplified by the new treatment forms]. DER NERVENARZT 2022; 93:122-134. [PMID: 35037966 PMCID: PMC8825642 DOI: 10.1007/s00115-021-01251-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 11/26/2021] [Indexed: 11/03/2022]
Abstract
BACKGROUND In recent years the possibilities for molecular diagnostics and treatment of rare childhood diseases have greatly improved. The first gene-modifying drugs have now been approved, leading to a new era of precision treatment in pediatric neurology. OBJECTIVE This article describes the dynamic developments of precision medicine in pediatric neurology in the areas of prevention, diagnostics and targeted treatment. DISCUSSION The paradigm shift as a result of precision medicine is based on a treatment approach focused more strongly on the individual and the corresponding unique characteristics. Modern methods of genetic and molecular diagnostics are used to accurately describe and characterize affected children, complemented by a precise description of the clinical phenotype. Nevertheless, the success of the best individual treatment strategy derived from this information is often dependent on the time of diagnosis. Therefore, methods for disease prevention, particularly newborn screening programs, become increasingly more important to achieve the best possible success of novel therapies even before the onset of disease symptoms. In addition to a precise stratification of therapies, special attention should be paid in the future to the consideration of the individual perspective of patients and parents/guardians. Furthermore, a normative framework for a quality-ensured application of gene-modifying therapies in the German healthcare system must be created.
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Affiliation(s)
- Andreas Ziegler
- Zentrum für Kinder- und Jugendmedizin, Sektion für Neuropädiatrie und Stoffwechselmedizin, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Deutschland.
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Damerval M, Fagnoni-Legat C, Louvrier A, Fischer S, Limat S, Clairet AL, Nerich V, Madelaine I, Kroemer M. ATMP Environmental Exposure Assessment in European Healthcare Settings: A Systematic Review of the Literature. Front Med (Lausanne) 2021; 8:713047. [PMID: 34926483 PMCID: PMC8671638 DOI: 10.3389/fmed.2021.713047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 10/18/2021] [Indexed: 12/19/2022] Open
Abstract
Since 2007, a new class of biologic products for human use called "advanced therapy medicinal products (ATMP)" have been legally integrated in the European Medical Agency. They consist of recombinant nucleic acid, engineered cells, cells, or tissues. In the United States, ATMP fall under the regulatory framework of biological products and the term "cell and gene therapy product" is used in the legislative and regulatory documents. Potential clinical applications are broad, particularly, in the field of cancer, inherited genetic disease, and regenerative medicine. Indeed, the benefit conferred by CD19 chimeric antigen receptor T cells led to the first engineered cell therapy products to be approved by the Food and Drug Administration (FDA) in 2017. Gene therapy products to treat orphan diseases are also extensively developed with many clinical trials ongoing in the world. Nevertheless, the use of these therapeutic products is complex and requires careful considerations in the terms of regulatory and hospital setting requirements, such as storage, handling, administration, and disposal which justify the implementation of a secured medication circuit. Through this systematic review of the literature, the authors wanted to compile data on the assessment of environmental exposure related to the use of ATMP in healthcare setting to secure their medication circuit. A literature search was conducted on PubMed and Web of Science, and 32 publications dealing with environmental exposure assessment and ATMP were selected. In addition, marketed ATMPs were identified and data regarding the environmental concerns were extracted from product information sections from European Public Assessment Reports (EPAR). The environmental contamination assessments were mainly addressed in the reviews rather than in original articles related to the use of ATMP. Most of the product information sections from EPAR suggested precautions rather than requirements when dealing with environmental consideration following ATMP handling. Nevertheless, these precautions usually remain elusive especially concerning waste disposal and the detection of biological material on the work surfaces, and mainly relate to the genetically modified organisms (GMO) over non-GMO cellular products. Pharmaceutical oversight and adherence to the good preparation practices and good clinical practices are essential to ensure the safe use in term of environmental concern of these new therapeutic products in healthcare setting.
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Affiliation(s)
- Margaux Damerval
- Department of Pharmacy, University Hospital of Besançon, Besançon, France
| | | | - Aurélien Louvrier
- Host-Graft Interactions Lab – Tumor - Cell and Tissue engineering (UMR 1098 INSERM/UFC/EFS), University of Franche-Comté, Besançon, France
- Department of Oral and Maxillofacial Surgery, University Hospital of Besançon, Besançon, France
| | - Sarah Fischer
- Department of Pharmacy, University Hospital of Besançon, Besançon, France
| | - Samuel Limat
- Department of Pharmacy, University Hospital of Besançon, Besançon, France
- Department of Oral and Maxillofacial Surgery, University Hospital of Besançon, Besançon, France
| | - Anne-Laure Clairet
- Department of Pharmacy, University Hospital of Besançon, Besançon, France
| | - Virginie Nerich
- Department of Pharmacy, University Hospital of Besançon, Besançon, France
- Department of Oral and Maxillofacial Surgery, University Hospital of Besançon, Besançon, France
| | | | - Marie Kroemer
- Department of Pharmacy, University Hospital of Besançon, Besançon, France
- Department of Oral and Maxillofacial Surgery, University Hospital of Besançon, Besançon, France
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9
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Behl T, Kaur I, Kumar A, Mehta V, Zengin G, Arora S. Gene Therapy in the Management of Parkinson's Disease: Potential of GDNF as a Promising Therapeutic Strategy. Curr Gene Ther 2021; 20:207-222. [PMID: 32811394 DOI: 10.2174/1566523220999200817164051] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 06/14/2020] [Accepted: 07/15/2020] [Indexed: 12/13/2022]
Abstract
The limitations of conventional treatment therapies in Parkinson's disorder, a common neurodegenerative disorder, lead to the development of an alternative gene therapy approach. Multiple treatment options targeting dopaminergic neuronal regeneration, production of enzymes linked with dopamine synthesis, subthalamic nucleus neurons, regulation of astrocytes and microglial cells and potentiating neurotrophic factors, were established. Viral vector-based dopamine delivery, prodrug approaches, fetal ventral mesencephalon tissue transplantation and dopamine synthesizing enzyme encoding gene delivery are significant therapies evidently supported by numerous trials. The review primarily elaborates on the significant role of glial cell-line derived neurotrophic factor in alleviating motor symptoms and the loss of dopaminergic neurons in Parkinson's disease. Neuroprotective and neuroregenerative effects of GDNF were established via preclinical and clinical study outcomes. The binding of GDNF family ligands with associated receptors leads to the formation of a receptor-ligand complex activating Ret receptor of tyrosine kinase family, which is only expressed in dopaminergic neurons, playing an important role in Parkinson's disease, via its association with the essential protein encoded genes. Furthermore, the review establishes delivery aspects, like ventricular delivery of recombinant GDNF, intraparenchymal and intraputaminal delivery using infusion catheters. The review highlights problems and challenges of GDNF delivery, and essential measures to overcome them, like gene therapy combinations, optimization of delivery vectors, newer targeting devices, motor symptoms curbing focused ultrasound techniques, modifications in patient selection criteria and development of novel delivery strategies based on liposomes and encapsulated cells, to promote safe and effective delivery of neurotrophic factor and establishment of routine treatment therapy for patients.
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Affiliation(s)
- Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Ishnoor Kaur
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Arun Kumar
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | | | - Gokhan Zengin
- Department of Biology, Faculty of Science, Selcuk University Campus, Konya, Turkey
| | - Sandeep Arora
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
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10
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García-González J, Marhuenda-Castillo S, Romero-Carretero S, Beltrán-García J. New era of personalized medicine: Advanced therapy medicinal products in Europe. World J Immunol 2021; 11:1-10. [DOI: 10.5411/wji.v11.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/24/2021] [Accepted: 06/07/2021] [Indexed: 02/06/2023] Open
Abstract
Advanced therapy medicinal products are human medical therapies based on genes, cells, or tissues, and due to their characteristics, they offer new innovative opportunities for the treatment of diseases and injuries, especially for diseases beyond the reach of traditional approaches. These therapies are at the forefront of innovation and have historically been very controversial, although in the last decade they have gained prominence while the number of new advanced therapies has increased every year. In this regard, despite the controversy they may generate, they are expected to dominate the market in the coming decades. Technologies based on advanced therapies are the present and future of medicine and bring us closer to the long-awaited precision medicine. Here we review the field as it stands today, with a focus on the molecular mechanisms that guided the different advanced therapies approved by the European Medicines Agency, their current status, and their legal approval.
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Affiliation(s)
| | | | | | - Jesús Beltrán-García
- Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia, Valencia 46010, Spain
- Center for Biomedical Research in Rare Diseases Network (CIBERER), Carlos III Health Institute, Valencia 46010, Spain
- INCLIVA Institute of Sanitary Research, Valencia 46010, Spain
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11
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Mansouri V, Beheshtizadeh N, Gharibshahian M, Sabouri L, Varzandeh M, Rezaei N. Recent advances in regenerative medicine strategies for cancer treatment. Biomed Pharmacother 2021; 141:111875. [PMID: 34229250 DOI: 10.1016/j.biopha.2021.111875] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 06/23/2021] [Accepted: 06/28/2021] [Indexed: 02/07/2023] Open
Abstract
Cancer stands as one of the most leading causes of death worldwide, while one of the most significant challenges in treating it is revealing novel alternatives to predict, diagnose, and eradicate tumor cell growth. Although various methods, such as surgery, chemotherapy, and radiation therapy, are used today to treat cancer, its mortality rate is still high due to the numerous shortcomings of each approach. Regenerative medicine field, including tissue engineering, cell therapy, gene therapy, participate in cancer treatment and development of cancer models to improve the understanding of cancer biology. The final intention is to convey fundamental and laboratory research to effective clinical treatments, from the bench to the bedside. Proper interpretation of research attempts helps to lessen the burden of treatment and illness for patients. The purpose of this review is to investigate the role of regenerative medicine in accelerating and improving cancer treatment. This study examines the capabilities of regenerative medicine in providing novel cancer treatments and the effectiveness of these treatments to clarify this path as much as possible and promote advanced future research in this field.
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Affiliation(s)
- Vahid Mansouri
- Gene Therapy Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Regenerative Medicine group (REMED), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Nima Beheshtizadeh
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Iran; School of Engineering, Faculty of Science and Engineering, Macquarie University, Sydney, NSW 2109, Australia; Regenerative Medicine group (REMED), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
| | - Maliheh Gharibshahian
- Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran; Regenerative Medicine group (REMED), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Leila Sabouri
- Regenerative Medicine group (REMED), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mohammad Varzandeh
- Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran; Regenerative Medicine group (REMED), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
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12
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Tomeo F, Mariz S, Brunetta AL, Stoyanova-Beninska V, Penttila K, Magrelli A. Haemophilia, state of the art and new therapeutic opportunities, a regulatory perspective. Br J Clin Pharmacol 2021; 87:4183-4196. [PMID: 33772837 PMCID: PMC8596702 DOI: 10.1111/bcp.14838] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 03/04/2021] [Accepted: 03/16/2021] [Indexed: 12/13/2022] Open
Abstract
Haemophilia A and B are rare bleeding disorders. Over the past decades, they have been transformed from debilitating diseases to manageable conditions in the Western world. However, optimizing haemophilia care remains challenging in developing countries. Several challenges and unmet needs remain in the treatment of the haemophilia limiting the QoL of patients. These challenges are now being addressed by extended half‐life recombinant factors, rebalancing and substitution therapies. Gene therapy and genome editing show promise for a definite clinical cure. Here, we provide an overview of new therapeutic opportunities for haemophilia and their advances and limitations from a regulatory perspective. The database on human medicines from the European Medicines Agency (EMA) was used and data from rare disease (orphan) designations and EPARs were retrieved for the analysis. Clinical trial databases were used to query all active studies on haemophilia. Gene therapy medicinal products based on AAV and lentiviral vectors are in development and clinical trials have reported substantial success in ameliorating bleeding tendency in haemophilia patients. The prospect of gene editing for correction of the underlying mutation is on the horizon and has considerable potential. With regard to the benefit of the gene therapy medicinal products, more long‐term efficacy and safety data are awaited. We are entering an era of innovation and abundance in treatment options for those affected by bleeding disorders, but issues remain about the affordability and accessibility to patients.
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Affiliation(s)
| | - Segundo Mariz
- Orphan Office, European Medicines Agency, Amsterdam, The Netherlands
| | - Angelo Loris Brunetta
- Italian Foundation 'L.Giambrone' for the cure of Thalassemia, Castel Volturno, Italy
| | | | | | - Armando Magrelli
- National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy
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13
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Qiu T, Wang Y, Dabbous M, Hanna E, Han R, Liang S, Toumi M. Current state of developing advanced therapies for rare diseases in the European Union. Expert Opin Orphan Drugs 2020. [DOI: 10.1080/21678707.2020.1835640] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Tingting Qiu
- Department of Public Health, Aix-Marseille University, Marseille, France
| | - Yitong Wang
- Department of Public Health, Aix-Marseille University, Marseille, France
| | - Monique Dabbous
- Department of Public Health, Aix-Marseille University, Marseille, France
| | - Eve Hanna
- Department of Price, Reimbursement and Market Access, Creativ-ceutical, Paris, France
| | - Ru Han
- Department of Public Health, Aix-Marseille University, Marseille, France
| | - Shuyao Liang
- Department of Public Health, Aix-Marseille University, Marseille, France
| | - Mondher Toumi
- Department of Public Health, Aix-Marseille University, Marseille, France
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Childs PG, Reid S, Salmeron-Sanchez M, Dalby MJ. Hurdles to uptake of mesenchymal stem cells and their progenitors in therapeutic products. Biochem J 2020; 477:3349-3366. [PMID: 32941644 PMCID: PMC7505558 DOI: 10.1042/bcj20190382] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 08/15/2020] [Accepted: 08/24/2020] [Indexed: 12/11/2022]
Abstract
Twenty-five years have passed since the first clinical trial utilising mesenchymal stomal/stem cells (MSCs) in 1995. In this time academic research has grown our understanding of MSC biochemistry and our ability to manipulate these cells in vitro using chemical, biomaterial, and mechanical methods. Research has been emboldened by the promise that MSCs can treat illness and repair damaged tissues through their capacity for immunomodulation and differentiation. Since 1995, 31 therapeutic products containing MSCs and/or progenitors have reached the market with the level of in vitro manipulation varying significantly. In this review, we summarise existing therapeutic products containing MSCs or mesenchymal progenitor cells and examine the challenges faced when developing new therapeutic products. Successful progression to clinical trial, and ultimately market, requires a thorough understanding of these hurdles at the earliest stages of in vitro pre-clinical development. It is beneficial to understand the health economic benefit for a new product and the reimbursement potential within various healthcare systems. Pre-clinical studies should be selected to demonstrate efficacy and safety for the specific clinical indication in humans, to avoid duplication of effort and minimise animal usage. Early consideration should also be given to manufacturing: how cell manipulation methods will integrate into highly controlled workflows and how they will be scaled up to produce clinically relevant quantities of cells. Finally, we summarise the main regulatory pathways for these clinical products, which can help shape early therapeutic design and testing.
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Affiliation(s)
- Peter G. Childs
- Centre for the Cellular Microenvironment, Division of Biomedical Engineering, School of Engineering, College of Science and Engineering, University of Glasgow, Glasgow G12 8QQ, U.K
- Centre for the Cellular Microenvironment, SUPA Department of Biomedical Engineering, University of Strathclyde, Glasgow G1 1QE, U.K
| | - Stuart Reid
- Centre for the Cellular Microenvironment, SUPA Department of Biomedical Engineering, University of Strathclyde, Glasgow G1 1QE, U.K
| | - Manuel Salmeron-Sanchez
- Centre for the Cellular Microenvironment, Division of Biomedical Engineering, School of Engineering, College of Science and Engineering, University of Glasgow, Glasgow G12 8QQ, U.K
| | - Matthew J. Dalby
- Centre for the Cellular Microenvironment, Institute for Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, U.K
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15
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Tang R, Xu Z. Gene therapy: a double-edged sword with great powers. Mol Cell Biochem 2020; 474:73-81. [DOI: 10.1007/s11010-020-03834-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 07/11/2020] [Indexed: 12/17/2022]
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16
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The approved gene therapy drugs worldwide: from 1998 to 2019. Biotechnol Adv 2020; 40:107502. [PMID: 31887345 DOI: 10.1016/j.biotechadv.2019.107502] [Citation(s) in RCA: 224] [Impact Index Per Article: 44.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 12/26/2019] [Accepted: 12/27/2019] [Indexed: 02/06/2023]
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17
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Oberweis CV, Marchal JA, López-Ruiz E, Gálvez-Martín P. A Worldwide Overview of Regulatory Frameworks for Tissue-Based Products. TISSUE ENGINEERING PART B-REVIEWS 2020; 26:181-196. [DOI: 10.1089/ten.teb.2019.0315] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Caroline Veronique Oberweis
- Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospitals of Granada—University of Granada, Granada, Spain
| | - Juan Antonio Marchal
- Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospitals of Granada—University of Granada, Granada, Spain
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain
- Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain
- Excellence Research Unit “Modeling Nature” (MNat), University of Granada, Granada, Spain
| | - Elena López-Ruiz
- Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospitals of Granada—University of Granada, Granada, Spain
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain
- Excellence Research Unit “Modeling Nature” (MNat), University of Granada, Granada, Spain
- Department of Health Sciences, University of Jaén, Jaén, Spain
| | - Patricia Gálvez-Martín
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Granada, Spain
- R&D Human Health, Bioibérica S.A.U., Barcelona, Spain
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18
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Comparative analysis of correlations of research and development indicators for rare diseases among Japan, the US, and Europe. Scientometrics 2019. [DOI: 10.1007/s11192-019-03129-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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19
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Hurdles in gene therapy regulatory approval: a retrospective analysis of European Marketing Authorization Applications. Drug Discov Today 2019; 24:823-828. [DOI: 10.1016/j.drudis.2018.12.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 12/02/2018] [Accepted: 12/18/2018] [Indexed: 02/06/2023]
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20
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Vella Bonanno P, Bucsics A, Simoens S, Martin AP, Oortwijn W, Gulbinovič J, Rothe C, Timoney A, Ferrario A, Gad M, Salem A, Hoxha I, Sauermann R, Kamusheva M, Dimitrova M, Petrova G, Laius O, Selke G, Kourafalos V, Yfantopoulos J, Magnusson E, Joppi R, Jakupi A, Bochenek T, Wladysiuk M, Furtado C, Marković-Peković V, Mardare I, Meshkov D, Fürst J, Tomek D, Cortadellas MO, Zara C, Haycox A, Campbell S, Godman B. Proposal for a regulation on health technology assessment in Europe - opinions of policy makers, payers and academics from the field of HTA. Expert Rev Pharmacoecon Outcomes Res 2019; 19:251-261. [PMID: 30696372 DOI: 10.1080/14737167.2019.1575730] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION In January 2018 the European Commission published a Proposal for a Regulation on Health Technology Assessment (HTA): 'Proposal for a Regulation on health technology assessment and amending Directive 2011/24/EU'. A number of stakeholders, including some Member States, welcomed this initiative as it was considered to improve collaboration, reduce duplication and improve efficiency. There were however a number of concerns including its legal basis, the establishment of a single managing authority, the preservation of national jurisdiction over HTA decision-making and the voluntary/mandatory uptake of joint assessments by Member States. Areas covered: This paper presents the consolidated views and considerations on the original Proposal as set by the European Commission of a number of policy makers, payers, experts from pricing and reimbursement authorities and academics from across Europe. Expert commentary: The Proposal has since been extensively discussed at Council and while good progress has been achieved, there are still divergent positions. The European Parliament gave a number of recommendations for amendments. If the Proposal is approved, it is important that a balanced, improved outcome is achieved for all stakeholders. If not approved, the extensive contribution and progress attained should be sustained and preserved, and the best alternative solutions found.
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Affiliation(s)
- Patricia Vella Bonanno
- a Strathclyde Institute of Pharmacy and Biomedical Sciences , University of Strathclyde , Glasgow , UK
| | - Anna Bucsics
- b Mechanism of Coordinated Access to Orphan Medicinal Products (MoCA) , Brussels , Belgium
| | - Steven Simoens
- c KU Leuven Department of Pharmaceutical and Pharmacological Sciences , Leuven , Belgium
| | - Antony P Martin
- d Health Economics Centre , University of Liverpool Management School , Liverpool , UK
| | - Wija Oortwijn
- e Department for Health Evidence , Radboud University Medical Center , Nijmegen , The Netherlands
| | - Jolanta Gulbinovič
- f Department of Pathology, Forensic Medicine and Pharmacology , Institute of Biomedical Sciences, Faculty of Medicine, VilniusUniversity , Vilnius , Lithuania
| | - Celia Rothe
- g Department of Drug Management, Faculty of Health Sciences , Jagiellonian University Medical College , Krakow , Poland
| | - Angela Timoney
- a Strathclyde Institute of Pharmacy and Biomedical Sciences , University of Strathclyde , Glasgow , UK.,h NHS Lothian , Edinburgh , UK
| | - Alessandra Ferrario
- i Division of Health Policy and Insurance Research, Department of Population Medicine , Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston , MA , USA
| | - Mohamed Gad
- j Global Health and Development Group , Imperial College , London , UK
| | | | - Iris Hoxha
- l Department of Pharmacy, Faculty of Medicine , University of Medicine , Tirana , Albania
| | - Robert Sauermann
- m Hauptverband der ÖsterreichischenSozialversicherungsträger , Vienna , Austria
| | - Maria Kamusheva
- n Department of Organization and Economics of Pharmacy, Faculty of Pharmacy , Medical University-Sofia , Bulgaria
| | - Maria Dimitrova
- n Department of Organization and Economics of Pharmacy, Faculty of Pharmacy , Medical University-Sofia , Bulgaria
| | - Guenka Petrova
- n Department of Organization and Economics of Pharmacy, Faculty of Pharmacy , Medical University-Sofia , Bulgaria
| | - Ott Laius
- o State Agency of Medicines , Tartu , Estonia
| | - Gisbert Selke
- p Wissenschaftliches Institut der AOK (WidO) , Berlin , Germany
| | - Vasilios Kourafalos
- q EOPYY-National Organization for the Provision of Healthcare Services , Athens , Greece
| | - John Yfantopoulos
- r School of Economics and Political Science , University of Athens , Athens , Greece
| | - Einar Magnusson
- s Department of Health Services , Ministry of Health , Reykjavík , Iceland
| | - Roberta Joppi
- t Pharmaceutical Drug Department , Azienda Sanitaria Locale of Verona , Verona , Italy
| | | | - Tomasz Bochenek
- g Department of Drug Management, Faculty of Health Sciences , Jagiellonian University Medical College , Krakow , Poland
| | | | | | - Vanda Marković-Peković
- x Ministry of Health and Social Welfare , Banja Luka , Republic of Srpska, Bosnia and Herzegovina.,y Department of Social Pharmacy , University of Banja Luka, Faculty of Medicine , Banja Luka , Republic of Srpska, Bosnia and Herzegovina
| | - Ileana Mardare
- z Faculty of Medicine, Public Health and Management Department , "Carol Davila" University of Medicine and Pharmacy Bucharest , Bucharest , Romania
| | - Dmitry Meshkov
- aa National Research Institution for Public Health , Moscow , Russia
| | - Jurij Fürst
- ab Health Insurance Institute , Ljubljana , Slovenia
| | - Dominik Tomek
- ac Faculty of Medicine, Slovak Medical University , Bratislava , Slovakia
| | | | - Corrine Zara
- ad Drug Territorial Action Unit , Catalan Health Service , Barcelona , Spain
| | - Alan Haycox
- d Health Economics Centre , University of Liverpool Management School , Liverpool , UK
| | - Stephen Campbell
- ae Centre for Primary Care, Division of Population Health, Health Services Research and Primary Care , University of Manchester , Manchester , UK.,af NIHR Greater Manchester Patient Safety Translational Research Centre, School of Health Sciences , University of Manchester , Manchester , UK
| | - Brian Godman
- a Strathclyde Institute of Pharmacy and Biomedical Sciences , University of Strathclyde , Glasgow , UK.,d Health Economics Centre , University of Liverpool Management School , Liverpool , UK.,ag Division of Clinical Pharmacology , Karolinska, Karolinska Institutet , Stockholm , Sweden.,ah Department of Public Health Pharmacy and Management, School of Pharmacy , Sefako Makgatho Health Sciences University , Garankuwa , South Africa
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Del Pozo-Rodríguez A, Rodríguez-Gascón A, Rodríguez-Castejón J, Vicente-Pascual M, Gómez-Aguado I, Battaglia LS, Solinís MÁ. Gene Therapy. ADVANCES IN BIOCHEMICAL ENGINEERING/BIOTECHNOLOGY 2019; 171:321-368. [PMID: 31492963 DOI: 10.1007/10_2019_109] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gene therapy medicinal products (GTMPs) are one of the most promising biopharmaceuticals, which are beginning to show encouraging results. The broad clinical research activity has been addressed mainly to cancer, primarily to those cancers that do not respond well to conventional treatment. GTMPs to treat rare disorders caused by single-gene mutations have also made important advancements toward market availability, with eye and hematopoietic system diseases as the main applications.Nucleic acid-marketed products are based on both in vivo and ex vivo strategies. Apart from DNA-based therapies, antisense oligonucleotides, small interfering RNA, and, recently, T-cell-based therapies have been also marketed. Moreover, the gene-editing tool CRISPR is boosting the development of new gene therapy-based medicines, and it is expected to have a substantial impact on the gene therapy biopharmaceutical market in the near future.However, despite the important advancements of gene therapy, many challenges have still to be overcome, which are discussed in this book chapter. Issues such as efficacy and safety of the gene delivery systems and manufacturing capacity of biotechnological companies to produce viral vectors are usually considered, but problems related to cost and patient affordability must be also faced to ensure the success of this emerging therapy. Graphical Abstract.
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Affiliation(s)
- Ana Del Pozo-Rodríguez
- Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
| | - Alicia Rodríguez-Gascón
- Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
| | - Julen Rodríguez-Castejón
- Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
| | - Mónica Vicente-Pascual
- Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
| | - Itziar Gómez-Aguado
- Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
| | - Luigi S Battaglia
- Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Turin, Italy
| | - María Ángeles Solinís
- Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain.
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de Wilde S, Coppens DG, Hoekman J, de Bruin ML, Leufkens HG, Guchelaar HJ, Meij P. EU decision-making for marketing authorization of advanced therapy medicinal products: a case study. Drug Discov Today 2018; 23:1328-1333. [DOI: 10.1016/j.drudis.2018.03.008] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Revised: 01/31/2018] [Accepted: 03/15/2018] [Indexed: 12/28/2022]
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Van Pham P, Nguyen HT, Vu NB. Evolution of Stem Cell Products in Medicine: Future of Off-the-Shelf Products. STEM CELL DRUGS - A NEW GENERATION OF BIOPHARMACEUTICALS 2018. [DOI: 10.1007/978-3-319-99328-7_6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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