scholarly journals Full GMP-Compliant Validation of Bone Marrow-Derived Human CD133+Cells as Advanced Therapy Medicinal Product for Refractory Ischemic Cardiomyopathy

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Daniela Belotti ◽  
Giuseppe Gaipa ◽  
Beatrice Bassetti ◽  
Benedetta Cabiati ◽  
Gabriella Spaltro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ischemic Cardiomyopathy ◽  
Quality And Safety ◽  
Ischemic Heart Failure ◽  
Medicinal Products ◽  
Controlled Clinical Trials ◽  
Advanced Therapy Medicinal Product ◽  
Safety Standards ◽  
Regulatory Frameworks ◽  
Advanced Therapy

According to the European Medicine Agency (EMA) regulatory frameworks, Advanced Therapy Medicinal Products (ATMP) represent a new category of drugs in which the active ingredient consists of cells, genes, or tissues. ATMP-CD133 has been widely investigated in controlled clinical trials for cardiovascular diseases, making CD133+cells one of the most well characterized cell-derived drugs in this field. To ensure high quality and safety standards for clinical use, the manufacturing process must be accomplished in certified facilities following standard operative procedures (SOPs). In the present work, we report the fully compliant GMP-grade production of ATMP-CD133 which aims to address the treatment of chronic refractory ischemic heart failure. Starting from bone marrow (BM), ATMP-CD133 manufacturing output yielded a median of 6.66 × 106of CD133+cells (range 2.85 × 106–30.84 × 106), with a viability ranged between 96,03% and 99,97% (median 99,87%) and a median purity of CD133+cells of 90,60% (range 81,40%–96,20%). Based on these results we defined our final release criteria for ATMP-CD133: purity ≥ 70%, viability ≥ 80%, cellularity between 1 and 12 × 106cells, sterile, and endotoxin-free. The abovementioned criteria are currently applied in our Phase I clinical trial (RECARDIO Trial).

scholarly journals Phage Therapy Regulation: From Night to Dawn

Viruses ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 352 ◽  
Author(s):  
Alan Fauconnier
Keyword(s):  
Large Scale ◽  
Phage Therapy ◽  
Resistance To Change ◽  
Regulatory Framework ◽  
Global Perspective ◽  
Western World ◽  
Medicinal Products ◽  
Advanced Therapy Medicinal Product ◽  
Advanced Therapy ◽  
And Personalized Medicine

After decades of disregard in the Western world, phage therapy is witnessing a return of interest. However, the pharmaceutical legislation that has since been implemented is basically designed for regulating industrially-made pharmaceuticals, devoid of any patient customization and intended for large-scale distribution. Accordingly, the resulting regulatory framework is hardly reconcilable with the concept of sustainable phage therapy, involving tailor-made medicinal products in the global perspective of both evolutionary and personalized medicine. The repeated appeal for a dedicated regulatory framework has not been heard by the European legislature, which, in this matter, features a strong resistance to change despite the precedent of the unhindered implementation of advanced therapy medicinal product (ATMPs) regulation. It is acknowledged that in many aspects, phage therapy medicinal products are quite unconventional pharmaceuticals and likely this lack of conformity to the canonical model hampered the development of a suitable regulatory pathway. However, the regulatory approaches of countries where phage therapy traditions and practice have never been abandoned are now being revisited by some Western countries, opening new avenues for phage therapy regulation. As a next step, supranational and international organizations are urged to take over the initiatives originally launched by national regulatory authorities.

scholarly journals Measures to minimize cross-contamination risks in Advanced Therapy Medicinal Product manufacturing

2014 ◽  
Author(s):  
Livia Roseti ◽  
Marta Serra ◽  
Brunella Grigolo
Keyword(s):  
Medicinal Product ◽  
Main Product ◽  
Good Manufacturing Practice ◽  
Cross Contamination ◽  
Medicinal Products ◽  
Advanced Therapy Medicinal Product ◽  
Advanced Therapy ◽  
European Regulations ◽  
Product Manufacturing

Current European regulations define in vitro expanded cells for clinical purposes as substantially manipulated and include them in the class of Advanced Therapy Medicinal Products to be manufactured in compliance with current Good Manufacturing Practice. These quality requirements are generally thought to be elaborate and costly. However they ensure three main product characteristics: safety, consistency and absence of cross-contamination. The term cross-contamination is used to indicate misidentification of one cell line or culture by another. The Good Manufacturing Practice Guidelines suggest some recommendations in order to prevent cross-contaminations and require a demonstration that the implemented actions are effective. Here we report some practical examples useful both to minimize cross-contamination risks in an Advanced Therapy Medicinal Product production process and to evaluate the efficacy of the adopted measures.

scholarly journals Towards an advanced therapy medicinal product based on mesenchymal stromal cells isolated from the umbilical cord tissue: quality and safety data

2014 ◽  
Vol 5 (1) ◽  
pp. 9 ◽  
Author(s):  
José Paulo Martins ◽  
Jorge Miguel Santos ◽  
Joana Marto de Almeida ◽  
Mariana Alves Filipe ◽  
Mariana Vargas Teixeira de Almeida ◽  
...  
Keyword(s):  
Medicinal Product ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Safety Data ◽  
Quality And Safety ◽  
Tissue Quality ◽  
Advanced Therapy Medicinal Product ◽  
Advanced Therapy ◽  
Umbilical Cord Tissue

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 Non-hematopoietic essential functions of bone marrow cells: a review of scientific and clinical literature and rationale for treating bone defects

2015 ◽  
Vol 7 (4) ◽  
Author(s):  
David B. Harrell ◽  
Eugenio Caradonna ◽  
Laura Mazzucco ◽  
Rosmarie Gudenus ◽  
Berthold Amann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Bone Defects ◽  
European Medicines Agency ◽  
Iliac Crest Bone Graft ◽  
Advanced Therapy Medicinal Product ◽  
Advanced Therapy ◽  
Advanced Therapies ◽  
Marrow Cells

Hematopoiesis as the only essential function of bone marrow cells has been challenged for several decades through basic science (<em>in</em> <em>vitro</em> and <em>in</em> <em>vivo</em>) and clinical data. Such work has shed light on two other essential functions of bone marrow cells: osteopoiesis and angiogenesis/vasculogenesis. Clinical utility of autologous concentrated bone marrow aspirate (CBMA) has demonstrated both safety and efficacy in treating bone defects. Moreover, CBMA has been shown to be comparable to the gold standard of iliac crest bone graft (ICBG), or autograft, with regard to being osteogenic and osteoinductive. ICBG is not considered an advanced therapy medicinal product (ATMP), but CBMA may become regulated as an ATMP. The European Medicines Agency Committee for Advanced Therapies (EMA:CAT) has issued a reflection paper (20 June 2014) in which reversal of the 2013 ruling that CBMA is a non-ATMP has been proposed. We review bone marrow cell involvement in osteopoiesis and angiogenesis/vasculogenesis to examine EMA:CAT 2013 decision to use CBMA for treatment of osteonecrosis (<em>e.g</em>, of the femoral head) should be considered a non-ATMP. This paper is intended to provide discussion on the 20 June 2014 reflection paper by reviewing two non-hematopoietic essential functions of bone marrow cells. Additionally, we provide clinical and scientific rationale for treating osteonecrosis with CBMA.

Advanced Therapy Medicinal Products for Unmet Clinical Needs: Bone Marrow-Derived Mesenchymal Stem Cell to Treat Airway Defects

Cytotherapy ◽  
2016 ◽  
Vol 18 (6) ◽  
pp. S81
Author(s):  
T. Montemurro ◽  
S. Budelli ◽  
M. Viganò ◽  
C. Lavazza ◽  
E. Montelatici ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Medicinal Products ◽  
Advanced Therapy Medicinal Products ◽  
Advanced Therapy

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.

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