scholarly journals Biodistribution of Mesenchymal Stem/Stromal Cells in a Preclinical Setting

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Luc Sensebé ◽  
Sandrine Fleury-Cappellesso
Keyword(s):  
Stromal Cells ◽  
Tissue Repair ◽  
The United States ◽  
Immune Disorders ◽  
Medicinal Products ◽  
Safety Testing ◽  
Advanced Therapy ◽  
Good Manufacturing Practices ◽  
Cell Source ◽  
Somatic Cell Therapy

Due to their multi/pluripotency and immunosuppressive properties, mesenchymal stem/stromal cells (MSCs) are important tools for treatment of immune disorders and tissue repair. The increasing uses of MSCs lead to the development of production processes that need to be in accordance with good manufacturing practices (GMP). In Europe, MSCs are somatic cell-therapy products, referred to as advanced-therapy medicinal products (ATMPs), and in the United States MSCs must comply with current good tissue practice requirements. The safety and efficacy of MSCs must be ensured, whatever the cell source, and studies of dose and biodistribution are important aspects of safety testing. Preclinical data on biodistribution and pharmacodynamics are mandatory for approval. It is important to demonstrate that MSCs do not have unwanted homing that could drive to inappropriate differentiation in some organ or to support cancer development as suggested in some experiments. All these aspects should be addressed in a risk-based approach according to recently published guidelines by EMA. In the present article, we summarize the main approaches for labeling and tracking of infused MSCs, report on current animal models, and give an overview of available results on biodistribution.

THE PROBLEMATIC ASPECTS OF THE HOSPITAL EXEMPTION REGULATION FOR ADVANCED THERAPY MEDICINAL PRODUCTS

2014 ◽  
Vol 21 (1) ◽  
pp. 93-99
Author(s):  
Tatjana Ivaškienė
Keyword(s):  
Industrial Process ◽  
Medical Practitioner ◽  
Pharmaceutical Products ◽  
Medicinal Products ◽  
Member States ◽  
Advanced Therapy Medicinal Products ◽  
Advanced Therapy ◽  
Somatic Cell Therapy ◽  
Special Rules ◽  
Set Up

Advanced therapy medicinal products – new category of biological pharmaceutical products, which covers somatic cell therapy, gene therapy, tissue-engineered products and combined advanced therapy medicinal products. Regulation (EC) No 1394/2007 defined advanced therapy medicinal products and set up special rules for advanced therapy medicinal products intended to be placed on the market in Member States and prepared industrially or manufactured by a method involving an industrial process. The scope of Regulation (EC) No 1394/2007 is not applicable for advanced therapy medicinal products which are prescribed under the exclusive professional responsibility of a medical practitioner, prepared on a non-routine basis according to specific quality standards and used within the same Member State in a hospital, but at the same time it is stressed that Comunity rules related to quality and safety should not be breaked for these products. For this purpose Member States should provide

PP61 Advanced Therapy Medicinal Products Germany: Drugs Or Methods Review?

2019 ◽  
Vol 35 (S1) ◽  
pp. 48-49
Author(s):  
Elvira Müller ◽  
Kurt Neeser ◽  
Ilse-Barbara Oelze
Keyword(s):  
Treatment Method ◽  
Point Of View ◽  
Benefit Assessment ◽  
Grey Zone ◽  
Medicinal Products ◽  
Advanced Therapy Medicinal Products ◽  
Social Law ◽  
Ambiguous Situation ◽  
Advanced Therapy ◽  
Somatic Cell Therapy

IntroductionAdvanced Therapy Medicinal Products (ATMPs) comprise medicines for human use based on gene therapy, somatic cell therapy or bioprocessed tissue products. ATMPs are pharmaceutically manufactured drugs and mostly subject to central authorization requirements. In terms of social law, it is an ambiguous situation and more heterogeneously dealt with. ATMPs are assigned to method evaluation as well as to the Arzneimittelmarkt-Neuordnungsgesetz (AMNOG) procedure designated for drugs.MethodsGuidelines from Gemeinsame Bundesausschuss (G-BA), Institute for Quality and Efficiency in Health Care (IQWiG) and respective legislation, consultation results and methods/medical devices (MDs) evaluations according to §137h and for drugs according to AMNOG were reviewed and analyzed. Decision criteria and reasoning, assessment outcomes and potential impact on price negotiations were the main aspects for comparison.ResultsATMPs are subject to benefit assessment, with a decision at first on whether to be evaluated as a drug (e.g., Alofisel) or a method/device (e.g., Holoclar). By definition, an ATMP is classified as a treatment method, if the correct administration has at least the same significance for a successful therapy outcome as its mode of action. Depending on the respective decision, an evaluation as method follows or it must undergo the AMNOG process. According to G-BA's and IQWiG's point of view, randomized controlled trials (RCTs) are the “gold standard” for a benefit assessment of new therapies, including ATMPs. However, conduction of RCTs is not always possible for ATMPs which creates a disadvantage in the assessment right from the beginning. Otherwise no distinction is made between drugs and ATMPs in terms of reimbursement modalities. Outcomes based agreements could help overcoming inequalities and lead to quality-oriented reimbursement.ConclusionsATMPs represent a grey zone causing difficulties in classifying them either as method or drug. For individualized therapies evidence beyond RCTs and new reimbursement possibilities should be considered. Until new regulations are in place it is advisable to enter early into respective discussions with authorities.

scholarly journals Advanced Therapy Medicinal Products for the Eye: Definitions and Regulatory Framework

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 347
Author(s):  
Marina López-Paniagua ◽  
Ana de la Mata ◽  
Sara Galindo ◽  
Francisco Blázquez ◽  
Margarita Calonge ◽  
...  
Keyword(s):  
Legal Framework ◽  
Eye Diseases ◽  
The European Union ◽  
Medicinal Products ◽  
Therapeutic Approaches ◽  
Advanced Therapy Medicinal Products ◽  
Advanced Therapy ◽  
Innovative Products ◽  
Somatic Cell Therapy ◽  
Human Use

Advanced therapy medicinal products (ATMPs) are a group of innovative and complex biological products for human use that comprises somatic cell therapy medicinal products, tissue engineered products, gene therapy medicinal products, and the so-called combined ATMPs that consist of one of the previous three categories combined with one or more medical devices. During the last few years, the development of ATMPs for the treatment of eye diseases has become a fast-growing field as it offers the potential to find novel therapeutic approaches for treating pathologies that today have no cure or are just subjected to symptomatic treatments. Therefore, it is important for all professionals working in this field to be familiar with the regulatory principles associated with these types of innovative products. In this review, we outline the legal framework that regulates the development of ATMPs in the European Union and other international jurisdictions, and the criteria that each type of ATMP must meet to be classified as such. To illustrate each legal definition, ATMPs that have already completed the research and development stages and that are currently used for the treatment of eye diseases are presented as examples.

scholarly journals Human umbilical cord-derived mesenchymal stem/stromal cells: a promising candidate for the development of advanced therapy medicinal products

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Miryam Mebarki ◽  
Camille Abadie ◽  
Jérôme Larghero ◽  
Audrey Cras
Keyword(s):  
Umbilical Cord ◽  
Stromal Cells ◽  
Inflammatory Diseases ◽  
Late Phase ◽  
Human Umbilical Cord ◽  
Medicinal Products ◽  
Advanced Therapy Medicinal Products ◽  
Safety Issues ◽  
Advanced Therapy ◽  
Cell Banks

AbstractUmbilical cord-derived mesenchymal stem/stromal cells (UC-MSCs) emerge as a perspective for therapeutic use in immune and inflammatory diseases. Indeed, immunomodulatory and anti-inflammatory properties, associated to fewer ethical, availability, and safety issues, position UC-MSCs as a promising active substance to develop medicinal products. Since 2007, UC-MSC-based products are classified as advanced therapy medicinal products (ATMP) according to the European Regulation 1394/2007/EC. This new regulatory status required a total adaptation of stakeholders wishing to develop UC-MSC-based ATMPs. Cell production in tissue and cell banks has been replaced by the manufacturing of a medicine, in authorized establishments, according to the good manufacturing practices (GMP) specific to ATMPs. After a brief description of UC-MSCs, we described in this review their recent use in a large panel of immune and inflammatory pathologies, including early and late phase clinical trials. Despite the use of the same product, we noticed an important heterogeneity in terms of indication, posology and study design. Then, we discussed regulatory and manufacturing challenges for stakeholders, especially in terms of process harmonization and cells characterization. Our aim was to point that despite MSCs use for several decades, the development of an UC-MSC-based ATMP remains at this day a real challenge for both academic institutions and pharmaceutical companies.

Good Manufacturing Practices (GMP) manufacturing of advanced therapy medicinal products: a novel tailored model for optimizing performance and estimating costs

Cytotherapy ◽  
2013 ◽  
Vol 15 (3) ◽  
pp. 362-383 ◽  
Author(s):  
Mohamed Abou-El-Enein ◽  
Andy Römhild ◽  
Daniel Kaiser ◽  
Carola Beier ◽  
Gerhard Bauer ◽  
...  
Keyword(s):  
Medicinal Products ◽  
Advanced Therapy Medicinal Products ◽  
Advanced Therapy ◽  
Good Manufacturing Practices

scholarly journals Frontiers in non-union research

2020 ◽  
Vol 5 (10) ◽  
pp. 574-583
Author(s):  
Enrique Gómez-Barrena ◽  
Norma G. Padilla-Eguiluz ◽  
Philippe Rosset
Keyword(s):  
Bone Marrow ◽  
Bone Healing ◽  
Stromal Cells ◽  
Preclinical Studies ◽  
Medicinal Products ◽  
Non Union ◽  
Advanced Therapy ◽  
New Treatments ◽  
Product Definition ◽  
Science And Research

Multifactorial aetiology defines non-unions, with a biological and a mechanical distortion of the timeline of bone healing. Research on new advances to increase osteogenesis and promote non-union healing is strongly directed towards new forms of cell products. Basic science and research on non-union treatments is needed to compile preclinical data on new treatments. Bone marrow concentration and expanded mesenchymal stromal cells still require extensive clinical research to confirm efficacy in non-union treatment. Solid preclinical studies, precise cell product definition and preparation, and appropriate ethical and regulatory approvals are needed to assess new advanced therapy medicinal products. Cite this article: EFORT Open Rev 2020;5:574-583. DOI: 10.1302/2058-5241.5.190062

scholarly journals Systematic Review: Allogenic Use of Stromal Vascular Fraction (SVF) and Decellularized Extracellular Matrices (ECM) as Advanced Therapy Medicinal Products (ATMP) in Tissue Regeneration

2020 ◽  
Vol 21 (14) ◽  
pp. 4982 ◽  
Author(s):  
Pietro Gentile ◽  
Aris Sterodimas ◽  
Jacopo Pizzicannella ◽  
Laura Dionisi ◽  
Domenico De Fazio ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Stromal Vascular Fraction ◽  
Lateral Epicondylitis ◽  
Medicinal Products ◽  
Advanced Therapy Medicinal Products ◽  
Advanced Therapy ◽  
Meta Analyses ◽  
Clinical Experiments

Stromal vascular fraction (SVF) containing adipose stem cells (ASCs) has been used for many years in regenerative plastic surgery for autologous applications, without any focus on their potential allogenic role. Allogenic SVF transplants could be based on the possibility to use decellularized extracellular matrix (ECM) as a scaffold from a donor then re-cellularized by ASCs of the recipient, in order to develop the advanced therapy medicinal products (ATMP) in fully personalized clinical approaches. A systematic review of this field has been realized in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. Multistep research of the PubMed, Embase, MEDLINE, Pre-MEDLINE, PsycINFO, CINAHL, Clinicaltrials.gov, Scopus database, and Cochrane databases has been conducted to identify articles and investigations on human allogenic ASCs transplant for clinical use. Of the 341 articles identified, 313 were initially assessed for eligibility on the basis of the abstract. Of these, only 29 met all the predetermined criteria for inclusion according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach, and 19 have been included in quantitative synthesis (meta-analysis). Ninety-one percent of the studies previously screened (284 papers) were focused on the in vitro results and pre-clinical experiments. The allogenic use regarded the treatment of perianal fistulas, diabetic foot ulcers, knee osteoarthritis, acute respiratory distress syndrome, refractory rheumatoid arthritis, pediatrics disease, fecal incontinence, ischemic heart disease, autoimmune encephalomyelitis, lateral epicondylitis, and soft tissue defects. The information analyzed suggested the safety and efficacy of allogenic ASCs and ECM transplants without major side effects.

scholarly journals Price and reimbursement of advanced therapeutic medicinal products in Europe: are assessment and appraisal diverging from expert recommendations?

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Virginia Ronco ◽  
Myriam Dilecce ◽  
Elena Lanati ◽  
Pier Luigi Canonico ◽  
Claudio Jommi
Keyword(s):  
Selection Process ◽  
Grey Literature ◽  
Primary Objective ◽  
Medicinal Products ◽  
Health Authorities ◽  
Advanced Therapy ◽  
Additional Funding ◽  
Managed Entry Agreements ◽  
R Process ◽  
Expert Recommendations

Abstract Background Advanced therapy medicinal products (ATMPs) represent an important cornerstone for innovation in healthcare. However, uncertainty on the value, the high average cost per patient and their one-shot nature has raised a debate on their assessment and appraisal process for pricing and reimbursement (P&R) purposes. This debate led experts providing for recommendations on this topic. Our primary objective is to investigate the ATMPs P&R process in the main five European countries and to understand if this process is consistent with published P&R expert recommendations. We also investigated the current ATMP pipelines to understand if future ATMPs will create challenges for their P&R process. Methods P&R framework for ATMPs in the European Major five (EU5) countries was investigated through a literature search on PubMed, institutional websites of National Health Authorities and grey literature. The ATMPs pipeline database was populated from a clinical trial database (clinicaltrials.gov), relying on inclusion and exclusion criteria retrieved from the literature. Results Reimbursement status of ATMPs is different across the EU5 countries, with the exception of CAR-Ts which are reimbursed in all countries. Standard P&R process in place for other medicinal products is extended to ATMPs, with the exception of some cases in Germany. List prices, where available, are high and, tend to be aligned across countries. Outcome-based Managed Entry Agreements (MEAs) have been extensively used for ATMPs. Extra-funds for hospitals managing ATMPs were provided only in Germany and, as additional fund per episode, in France. The accreditation process of hospitals for ATMPs management was in most countries managed by the national authorities. As far as ATMPs pipeline is concerned, ATMPs in development are mostly targeting non-rare diseases. Conclusions Expert recommendations for ATMPs P&R were partially applied: the role of outcome-based MEAs has increased and the selection process of the centres authorized to use these treatments has been enhanced; additional funding for ATMPs management to accredited centres has not been completely considered and annuity payment and broader perspective in cost considerations are far from being put in place. These recommendations should be considered for future P&R negotiations to pursue rational resource allocation and deal with budget constraints.

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