Gene Therapy Medicinal Products Research Articles

Are genetically modified protozoa eligible for ATMP status? Concerning the legal categorization of an oncolytic protozoan drug candidate.

Neospora caninum is an obligate intracellular protozoan that affects several animal species. It is not pathogenic for humans, and its ability to infect and lyse a variety of cells and stimulate the immune system makes it an interesting drug candidate in oncology. The intrinsic oncolytic properties of N. caninum have been confirmed in several preclinical models. Moreover, it can be modified to improve its safety and/or efficacy against cancer cells. In this study, we propose the legal categorization of this new biological drug candidate and the impact of modifications, notably the integration of a suicide gene, the deletion of a gene allowing its multiplication in healthy cells, and/or the insertion of a gene coding for a therapeutic protein into its genome. When unmodified, N. caninum can be categorized as a biological medicinal product, whereas modifications aimed at increasing its safety classify it as a Somatic Cell Therapy Medicinal Product, and modifications aiming to increase its efficacy or both safety and efficacy make it as a Gene Therapy Medicinal Product. This categorization is fundamental because it determines the guidelines applicable for preclinical development. These guidelines being numerous and complex, we have focused on the key requirements necessary for the development of the future medicinal product.

Pharmacovigilance of gene therapy medicinal products

Pharmacovigilance of gene therapy medicinal products

Advances and Challenges in the Development of Gene Therapy Medicinal Products for Rare Diseases.

The development of viral vectors and recombinant DNA technology since the 1960s has enabled gene therapy to become a real therapeutic option for several inherited and acquired diseases. After several ups and downs in the gene therapy field, we are currently living a new era in the history of medicine in which several ex vivo and in vivo gene therapies have reached maturity. This is testified by the recent marketing authorization of several gene therapy medicinal products. In addition, many others are currently under evaluation after exhaustive investigation in human clinical trials. In this review, we summarize some of the most significant milestones in the development of gene therapy medicinal products that have already facilitated the treatment of a significant number of rare diseases. Despite progresses in the gene therapy field, the transfer of these innovative therapies to clinical practice is also finding important restrictions. Advances and also challenges in the progress of gene therapy for rare diseases are discussed in this opening review of a Human Gene Therapy issue dedicated to the 30th annual Congress of the European Society for Gene and Cell Therapy.

Selection of appropriate non-clinical animal models to ensure translatability of novel AAV-gene therapies to the clinic.

Gene Therapy Medicinal Products consist of a recombinant nucleic acid intended for the modulation or manipulation of a genetic sequence. A single administration of a novel gene therapy has the potential to be curative, with a durable long-term benefit to patients. Adeno-associated viral vectors have become the viral vector of choice for in vivo delivery of therapeutic transgenes as they are mildly immunogenic, can effectively transduce a variety of human tissues and cells, and have low levels of genomic integration. Central to the effective translation of data generated in discovery studies to the clinic is the selection of appropriate animal species for pivotal non-clinical studies. This review aims to support the selection of appropriate animal models for non-clinical studies to advance the development of novel adeno-associated virus gene therapies.

Advanced Therapy Medicinal Products for Age-Related Macular Degeneration; Scaffold Fabrication and Delivery Methods.

Retinal degenerative diseases such as age-related macular degeneration (AMD) represent a leading cause of blindness, resulting in permanent damage to retinal cells that are essential for maintaining normal vision. Around 12% of people over the age of 65 have some form of retinal degenerative disease. Whilst antibody-based drugs have revolutionised treatment of neovascular AMD, they are only effective at an early stage and cannot prevent eventual progression or allow recovery of previously lost vision. Hence, there is a clear unmet need to find innovative treatment strategies to develop a long-term cure. The replacement of damaged retinal cells is thought to be the best therapeutic strategy for the treatment of patients with retinal degeneration. Advanced therapy medicinal products (ATMPs) are a group of innovative and complex biological products including cell therapy medicinal products, gene therapy medicinal products, and tissue engineered products. Development of ATMPs for the treatment of retinal degeneration diseases has become a fast-growing field of research because it offers the potential to replace damaged retinal cells for long-term treatment of AMD. While gene therapy has shown encouraging results, its effectiveness for treatment of retinal disease may be hampered by the body's response and problems associated with inflammation in the eye. In this mini-review, we focus on describing ATMP approaches including cell- and gene-based therapies for treatment of AMD along with their applications. We also aim to provide a brief overview of biological substitutes, also known as scaffolds, that can be used for delivery of cells to the target tissue and describe biomechanical properties required for optimal delivery. We describe different fabrication methods for preparing cell-scaffolds and explain how the use of artificial intelligence (AI) can aid with the process. We predict that combining AI with 3D bioprinting for 3D cell-scaffold fabrication could potentially revolutionise retinal tissue engineering and open up new opportunities for developing innovative platforms to deliver therapeutic agents to the target tissues.

Unlocking the value of innovative medicines: Insights from the advanced therapy medicinal products (ATMP) innovation systems in Germany and Sweden

ObjectivesGenerally low uptake in the advanced therapy medicinal products (ATMP) market and difficult patient access has been observed across Europe. The objective is to analyze the key challenges of the ATMP innovation ecosystem around R&D, entrepreneurial activities, framework conditions and legitimacy and to highlight how national level activities can impact on patient access to ATMPs in Sweden and Germany. MethodsAn exploratory case studies approach was applied for analyzing ATMP development and uptake in Sweden and Germany between 2010 and 2021. A mixed methods and multi-level approach was used to collect data, including desktop research and 17 expert interviews. ResultsGermany is performing well and apart from better patients' engagement has lower barriers for ATMP development and diffusion compared to Sweden. The main hindrances in Sweden include a lack of collaboration between stakeholders in translational research, conservative HTA assessment and lack of innovative payment models. Both countries could benefit from better streamlined regulation on different aspects around clinical trials (i.e. ranging from legislation on genetically modified organisms for gene therapy medicinal products and master file approach for raw materials). ConclusionsDespite a number of hindrances around ATMP development and uptake, the evidence in terms of technological development on the one side and unmet patient needs on the other side, shows that ATMPs will play an important role in the future of modern healthcare systems. It is clear that further national level collaboration between academic, clinical and industrial players is necessary to overcome the existing hindrances and boost further development of ATMPs in Europe.

Gene Therapy Medicinal Products: Non-clinical Safety Studies

Currently, gene therapy medicinal products (GTMPs) are actively developed in many countries, including the Russian Federation. However, the use of GTMPs raises class-specific safety concerns.The aim of the study was to determine the main requirements for non-clinical safety testing of GTMPs, to identify risks associated with these medicinal products, to establish criteria for expert assessments, and to find optimisation opportunities for GTMP non-clinical safety programmes, using Russian and international experience in the assessment of submissions and the registration of medicinal products of this class.The Russian Federation, the Eurasian Economic Union, the European Union, and the United States have created regulatory frameworks governing the lifecycle of GTMPs and continue improving these frameworks. The properties of GTMPs may create unique safety issues, such as insertional mutagenesis, unregulated transgene expression, long-term persistence and off-target spread, vertical germline transmission, and environmental risks. To account for these issues, a comprehensive non-clinical safety programme for GTMPs may require additional special studies along with the standard ones. This review focuses on the main approaches to designing non-cellular GTMP safety studies and evaluating the obtained results. The authors identified improvement opportunities for and problematic aspects of study design, as well as conditions for and limitations of nonclinical data extrapolation and clinical safety profile prediction. The continuous improvement and updating of the regulatory frameworks governing non-clinical studies of GTMPs mean that developers of non-clinical safety programmes for GTMPs should use all their experience, as well as relevant national and international guidelines and recommendations.

Regulatory Trends in the Nonclinical Development of Viral Vector-Based Gene Therapies: A Benchmark Analysis of Approved Products

As it is often the case with innovative technologies, regulatory agencies are highly demanding in product safety demonstration from those pioneering breakthrough therapy products. Since the first historically approved gene therapy medicinal product (Gencidine in 2003) by the Chinese National Medicinal Products Administration, gene therapy medicinal products have slowly been emerging in other regions, as illustrated by the first European-approved gene therapy medicinal product (Glybera in 2012) and the first US-approved product (Imlygic in 2015). From then, with the rise of new molecular technologies (e.g., non-viral and viral vector systems), an exponential growth of gene therapies development could be gauged with, for example, the approval of more than thirty gene therapies between 2016-2022. Using a method based on Preferred Reporting Items for Systematic reviews and Meta-Analyses principle, throughout different literature databases, this review is restricted to the evaluation of viral vector-based gene therapy medicinal products (VV-GTMPs). It also considered relevant guidelines and public assessment reports issued by the EMA and / or the FDA on the products these agencies approved. Then, a benchmark was performed to help stakeholders to identify regulatory trends and to design appropriate nonclinical programs establishing the benefit / risk ratio for patients to be enrolled in clinical trials. The analysis was focused on the nonclinical activities (pharmacology, biodistribution / persistence / shedding, and toxicology) performed by Applicants / Sponsors. As of 30 March 2023, 18 VV-GTMPs have been authorized by the EMA and 14 by the FDA to treat either orphan diseases or limited number of oncology patients. The majority of these therapies are based on adeno-associated or retroviral viruses (often lentiviruses able to transfect hematopoietic CD34+ cells or T-cells). Based on an analysis of the ongoing clinical trials, there is now a trend for developing gene therapies for larger patient populations. In conclusion, given the VV-GTMPs diversity and targeted indications, a “one-size fits all” nonclinical development plan cannot be considered by default. Instead, individual, risk-based, tailored nonclinical development programs appear more appropriate to assess such products, taking into consideration the lessons learned from the past. In such fast-evolving environment, regulatory agencies need to adapt their evaluation process very rapidly.

European Pharmacopoeia's Approach to Cell and Gene Therapy: Focus on How Gene Therapy Texts Are Evolving.

The European Pharmacopoeia (Ph. Eur.) constitutes single recognised common standard for the quality control of medicines in Europe, which is also applied in many countries worldwide. In 2000, the European Pharmacopoeia Commission (EPC), the decision-making body of the Ph. Eur., set out to elaborate a text on gene therapy products. This resulted in the publication of the widely used and much appreciated general chapter Gene transfer medicinal products for human use (5.14) in 2006, at a time when no gene therapy medicinal products were yet approved on the European market. As a general chapter, it is not legally binding, but it reflects the consensus of the European authorities. Now, more than two decades after the first initiative in the gene therapy field and with several gene therapy medicinal products launched in Europe, the EPC proposes a modernised approach and the creation of a general monograph, i.e. a legally binding standard. In addition to general requirements for gene therapy medicinal products, it is also envisaged that this general monograph will outline specific criteria for the classes of products already on the market, i.e. genetically modified human autologous cells, adeno-associated virus vectors for human use and recombinant oncolytic herpes simplex viruses for human use. It is also proposed to create a new general chapter, Additional information on gene therapy medicinal products for human use (5.34), comprising the remaining sections of Chap. 5.14, as well as a newly elaborated section on genetically modified bacterial cells.

Marketing Regulatory Oversight of Advanced Therapy Medicinal Products in Europe.

Advanced therapy medicinal products (ATMP) in the European Union (EU) are regulated by Regulation 1394/2007 and comprise gene and cell therapy and tissue-engineered products. Under this framework, ATMP are authorised by the centralised procedure, coordinated by the European Medicines Agency (EMA), whereas clinical trial authorisations remain at the remit of each National Competent Authority. The Committee for Advanced Therapies is responsible for the scientific evaluation of the marketing authorisation applications and for generating a draft opinion that goes to the Committee for Human Medicinal Products for a final opinion. For every application, data and information relating to manufacturing processes and quality control of the active substance and final product have to be submitted for assessment together with data from non-clinical and clinical safety and efficacy studies. Technical requirements for ATMP are defined in the legislation, and guidance for different products is available through several EMA/CAT guidelines.Due to the diverse and complex nature of ATMP, a need for some regulatory flexibility was recognised. Thus, a risk-based approach was introduced in Regulation 1394/2007 allowing adapted regulatory requirements. This has led, for instance, to the development of good manufacturing practice (GMP) guidelines specific for ATMP. This, together with enhanced regulatory support, has allowed an increasing number of successful marketing authorisation applications resulting in 25 licensed ATMP in the EU, mainly gene therapy medicinal products. The promise of messenger RNA and genome editing technologies as therapeutic tools make the future for these innovative medicinal products look even brighter.This chapter reviews the regulatory landscape together with some of the support initiatives developed for ATMP in the EU.

Regulatory Frameworks for Advanced Therapy Medicinal Products in Thailand.

Advanced Therapy Medicinal Products (ATMPs) are a new class of medicinal products that fall under the Drug Act. B.E.2510. The Medicines Regulation Division, a regulatory unit under the Thai Food and Drug Administration, takes responsibility for the regulation of ATMPs. This includes importing or manufacturing of ATMPs for clinical trials, GMP inspection, and marketing authorization. In Thailand, ATMPs have been classified into four groups: cell therapy medicinal products, gene therapy medicinal products, tissue-engineered products, and combined ATMPs. At present, the guidelines for biological products are applied to ATMP in clinical trials and marketing authorization applications. At the same time, the specific guidelines for ATMPs are under development. This chapter provides an overview of the Thai FDA regulatory oversight of ATMPs, which covers investigational ATMPs, GMP certification, and marketing authorization.

Clinical Trials on Advanced Therapy Investigational Medicinal Products in Spain (2004-2022): Experience and Challenges for the Future.

Clinical investigation is the basis for establishing how useful advanced therapy investigational medicinal products (ATiMP) are for the treatment of serious diseases.In Spain, clinical trials (CT) on ATiMP need to follow the general European legislation on CT with medicinal products plus some specific legislation and guidance depending on the type of ATiMP.This chapter describes the characteristics of CT on ATiMP authorized in Spain in the period 2004-2022 and the legislation applicable along this period. There are clear differences in the clinical trials conducted by non commercial and commercial sponsors: the first have been more involved in CT on somatic cell therapy medicinal products (sCTMP) and tissue-engineered products (TEP), while the second drive more the CT on gene therapy medicinal products (GTMP) in the last years. Difficulties of budget and resources especially by non-commercial sponsors to meet the regulatory requirements are highlighted. The importance of complying with transparency rules with respect to CT on ATiMP is also discussed.

HTA23 Restrictions and Real-World Evidence Requirements in the Health Technology Assessment of Gene Therapy Medicinal Products in Europe, Canada, Australia, and the United States

The emergence of gene therapy medicinal products (GTMP) has provided novel treatment options for rare diseases. Health technology assessment (HTA) agencies evaluate GTMPs but their reimbursement recommendations can differ, particularly the additional restrictions and real-world evidence (RWE) requirements. Our objective was to review the restrictions and RWE requirements included in HTAs of GTMPs.

RNA-based drugs and regulation: Toward a necessary evolution of the definitions issued from the European union legislation.

Many RNA-based drugs, both vaccines and non-vaccines, are under development or even approved. They include coding mRNAs and non-coding (nc) RNAs among them antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), micro-RNAs (miRNAs), small activating RNAs (saRNAs), RNA aptamers and RNA guides. According to the European Union (EU) legislation, these products can be currently categorized into different regulatory statuses, depending, for vaccines, on their target (infectious disease or not) and, for other drugs, on how they are obtained (chemically or biologically). This classification is fundamental to the type of marketing authorization (MA), and therefore to the controls to be performed, from preclinical stages through clinical trials to pharmacovigilance, to meet the safety requirements for patients. However, the current rules raise several problems, in particular the risk, because technology is evolving, to have similar RNA drugs being covered by very different legal statuses and the lack of international harmonization. The objectives of this study are (i) to review how RNA medicinal products are currently legally categorized in the EU and especially whether they fall under the status of gene therapy medicinal products (GTMP), a regulatory status belonging to advanced therapy medicinal products (ATMP), (ii) to discuss the issues generated by this classification, with a focus on the heterogeneity of statuses of these products, the differences with the American and ICH definitions and the potential impact on the safety requirements.

Efficacy, safety and cost of gene therapy medicinal products in the U.S. and Europe.

Gene or advanced therapy medicinal products (ATMPs) are evolving innovative products that have recently been attracting medical and healthcare attention. ATMPs are offering advanced techniques in treating certain conditions, including rare diseases. Meanwhile, the short- and long-term safety and efficacy of these products raise concerns. In this study, a comparative analysis of gene therapy medicinal products in the U.S. and E.U. was carried out to provide an overview of their efficacy and safety. Data up until 2019 were collected from the Food and Drug Administration (FDA) and European Medicines Agency (EMA) regarding approved gene therapy products. The FDA and EMA websites and published clinical trials were searched to extract the required information. A total of eight gene therapies were identified that had been approved in the U.S. and/or E.U. These products are approved to treat various health conditions in different populations. Their efficacy and safety were evaluated on the basis of completed and ongoing pivotal clinical trials. ATMPs offer potential management for genetic disorders and rare health conditions that are untreatable. However, one of the main concerns associated with these therapies is the small sample size that is included in the pivotal clinical trials. The uncertain efficacy, incomplete trials and serious adverse events could be challenges that make some of these products a last-line therapy.

A Room with a View (and with a Gene Therapy Drug): Gene Therapy Medicinal Products and Genetic Tourism in Europe.

In contrast to the extreme caution that has been imposed on genetic medical procedures, in European law genetic drugs, or medications, have found a legal loophole that allows flexible (perhaps too flexible) access to these drugs. In Europe, Gene Therapy Medicinal Products are a form of Advanced Therapy Medicinal Products and as such submitted to the marketing authorization procedure. However, there are legal mechanisms in place - such as compassionate use, named patient use, and hospital exception - that allow for their provision to patients without proper approval. This is not, de per se, problematic; the problem arises, though, because such mechanisms are neither properly regulated nor monitored, and their application differs substantially according to the jurisdiction. This disparity and lack of control have given rise to situations of genetic tourism, where patients in desperate need travel to so-called genetic paradises, looking for a miraculous, and extremely expensive cure. The outcome is sometimes tragic, endangering patients' safety and undermining confidence in genetic products.

Hurdles to the Adoption of Gene Therapy as a Curative Option for Transfusion-Dependent Thalassemia.

Beta-thalassemia is one of the most common monogenic disorders. Standard treatment of the most severe forms, i.e., transfusion-dependent thalassemia (TDT) with long-term transfusion and iron chelation, represents a considerable medical, psychological, and economic burden. Allogeneic hematopoietic stem cell transplantation from an HLA-identical donor is a curative treatment with excellent results in children. Recently, several gene therapy approaches were evaluated in academia or industry-sponsored clinical trials as alternative curative options for children and young adults without an HLA-identical donor. Gene therapy by addition of a functional beta-globin gene using self-inactivating lentiviral vectors in autologous stem cells resulted in transfusion independence for a majority of TDT patients across different age groups and genotypes, with a current follow-up of multiple years. More recently, promising results were reported in TDT patients treated with autologous hematopoietic stem cells edited with the clustered regularly interspaced short palindromic repeats-Cas9 technology targeting erythroid BCL11A expression, a key regulator of the normal switch from fetal to adult globin production. Patients achieved high levels of fetal hemoglobin allowing for discontinuation of transfusions. Despite remarkable clinical efficacy, 2 major hurdles to gene therapy access for TDT patients materialized in 2021: (1) a risk of secondary hematological malignancies that is complex and multifactorial in origin and not limited to the risk of insertional mutagenesis, (2) the cost—even in high-income countries—is leading to the arrest of commercialization in Europe of the first gene therapy medicinal product indicated for TDT despite conditional approval by the European Medicines Agency.

COVID-19 vaccine approvals: key lessons for mRNA therapeutics

The development of mRNA therapeutics is not a new phenomenon, but the key role played by mRNA-based vaccines in battling the COVID-19 pandemic has resulted a rapid acceleration in the development timeframe of this technology field. In a recent expert roundtable discussion, we spoke to a panel of experts within the field to better understand what lessons the vaccine and therapeutic fields can learn from each other. Here, we sum up some of their key thoughts. <div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/544f55bceea342b7b14d37488e0dc915.jpg" data-image="1"></div><div class="author-det"><h3 class="author-name" style="color:#5D538A;">Venkata Indurthi</h3><h5 class="author-title" style="color:#5D538A;">Vice President Research and Development, Aldevron</h5><p class="focus-visible" data-focus-visible-added="">Venkata SK Indurthi, PhD is the Vice President of research and development at Aldevron (est. 1998, www.aldevron.com), a biologicals CDMO with sites in Fargo ND and Madison WI. He received his bachelor’s in engineering in biotechnology from SRM university (Chennai, India) and his Ph.D. in Pharmaceutical Sciences from North Dakota State University (Fargo, ND). After completing graduate school, he joined Aldevron as an assay development scientist and was focused developing assay for GMP release for biologics (DNA, RNA and protein). He then transitioned to a role of senior scientist, Product and Process Design (PPD) where he led the development of Aldervon’s mRNA process and platform and more recently as the Director of R&amp;D where he established all the R&amp;D efforts for Aldevron. Dr. Indurthi leads efforts that to develop new platforms and innovative manufacturing processes for the company including (not limiting to) the mRNA platform, plasmid DNA, gene synthesis and cell free synthetic DNA platform. His team also focuses on the development of new products for the company such as enzymes with improved attributes (increased yield, stability or activity). Dr. Indurthi’s research interests focus on the development of biologics. Particularly, new platform development from idea conception to commercialization. He has developed processes that are currently used for GMP manufacturing. Dr. Indurthi is also the operational head for the Aldevron RNA services. </div></div></div><div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/4d1901ea5f7e4906a920be4245fc9039.jpeg" data-image="1"></div><div class="author-det"><h3 class="author-name" style="color:#007589;">Joseph Barberio</h3><h5 class="author-title" style="color:#007589;">Director, Process Development, Strand Therapeutics Inc.</h5> Joseph Barberio is a biochemist and molecular biologist with a proven track record of solving complex problems with innovative solutions. He is the Director of mRNA Process Development at Strand Therapeutics and oversees Strand’s manufacturing strategy to support clinical development. With over fifteen years of industry experience, Joe specializes in process and analytical development and has extensive expertise in manufacturing of both viral and RNA based gene therapy medicinal products. The majority of Joseph’s career has been focused on building platforms for small biotech organizations. Most recently at bluebird bio, he constructed and led the mRNA process development team, a group designed to enable gene editing programs. Earlier in his career, Joe held process development roles at Moderna, Percivia, and Acceleron Pharma. In addition to his work at Strand, Joseph also serves on the Board of Directors of Sophie’s Hope Foundation, a non-profit charity supporting research for glycogen storage disease type 1b (GSD1b). </div></div></div><div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/276f2895701f4c2e939bb8cc42991fec.jpg" data-image="1"></div><div class="author-det"><h3 class="author-name" style="color:#00A795;">Scott Zobbi</h3><h5 class="author-title" style="color:#00A795;">Senior Business Development Manager, Custom POROS Chromatography Resins, Thermo Fisher Scientific</h5> Scott Zobbi is a Senior Manager of Business Development for Custom POROS Resins within the Bioproduction Division at Thermo Fisher Scientific. Scott has a B.S. in Biology from University of Connecticut and an MBA from the University of Massachusetts. Scott has worked on chromatography applications in the biotech industry for decades with 22 years spent at Thermo Fisher Scientific. His expertise is finding solutions to complex separation challenges draws on his experience in cGMP manufacturing, process development, customer training, sales and product management. In his current role, Scott is responsible for managing globally the Custom POROS Resin program, including working with customers to identify needs, in-house R&amp;D to develop solutions, and POROS manufacturing to commercialize bioprocess resins for GMP applications. </div></div></div><div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://cdn.insights.bio/uploads/7f8ed4c095f842d490465df72352b91a.jpg" data-image="1"></div><div class="author-det"><h3 class="author-name" style="color: rgb(255, 127, 63);">Dr Christoph Kröner</h3><h5 class="author-title" style="color: rgb(255, 127, 63);">Director, DNA Process Development &amp; Cap Technology, BioNTech SE</h5> Christoph Kröner works as Director DNA Process Development &amp; Cap Technology at BioNTech RNA Pharmaceuticals GmbH with strong focus on developmental work for BioNTech’s various clinical projects using mRNA as drug substance. He has more than 10 years of experience working with nucleic acids like mRNAs. His work focused on mRNA-based therapeutics when he joined BioNTech in 2014 as a scientist. Christoph Kröner holds a diploma and PhD in chemistry from the University of Stuttgart, Germany. </div></div></div>

Advanced therapy medicinal products: Regulatory framework, hospital and pharmaceutical circuits in Europe and France

Advanced therapy medicinal products (ATMPs) represent a new class of biological medicines. The European regulation has classified ATMPs into three categories: gene therapy medicinal products, somatic cell therapy medicinal products, and Tissue-Engineered products. If one of these categories incorporates a medical device, the medicine is defined as a Combined ATMP. The specificity and complexity of these innovative drugs have required a complete reorganization of hospital and pharmaceutical circuits, from patient eligibility to drug administration. Indeed, increased interaction and collaboration between different healthcare professionals are essential in order to guarantee quality and safety of these innovative medicines.

CAR-T cells : comment le registre de l’EBMT monitore les activités en Europe, identifie les contraintes et prépare l’évolution des régulations

CAR-T Cells are gene therapy medicinal products, a subcategory of Advanced Therapy Medicinal Products as defined in the EC Regulation 1394/2007. They may represent the first example of such medicinal products that are industry-manufactured and commercialized on a large scale. Their very nature, their manufacturing processes, pricing and conditions upon which they were approved by regulatory agencies, all lead the latter to require long-term follow-up after marketing approval with a view for a better definition of CAR-T Cells safety profile and efficacy profile in real world conditions. Collection and analysis of data over a 15-year period of time represents a technical and political challenge. So does the a priori definition of data to be collected for a wealth of forthcoming analyses that focus on the interests of a variety of stakeholders. EBMT has been collecting and analyzing data on hematopoietic cell transplants for decades. EBMT currently works with many interested parties to collect data on patients treated with CAR-T Cells.