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 MSC Manufacturing for Academic Clinical Trials: From a Clinical-Grade to a Full GMP-Compliant Process

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1320
Author(s):  
Chantal Lechanteur ◽  
Alexandra Briquet ◽  
Virginie Bettonville ◽  
Etienne Baudoux ◽  
Yves Beguin
Keyword(s):  
Large Scale ◽  
Raw Materials ◽  
Good Manufacturing Practice ◽  
Phase Iii ◽  
Scale Production ◽  
Clinical Grade ◽  
Advanced Therapy Medicinal Product ◽  
Long Term Storage ◽  
Advanced Therapy ◽  
New Variant

Following European regulation 1394/2007, mesenchymal stromal cell (MSCs) have become an advanced therapy medicinal product (ATMP) that must be produced following the good manufacturing practice (GMP) standards. We describe the upgrade of our existing clinical-grade MSC manufacturing process to obtain GMP certification. Staff organization, premises/equipment qualification and monitoring, raw materials management, starting materials, technical manufacturing processes, quality controls, and the release, thawing and infusion were substantially reorganized. Numerous studies have been carried out to validate cultures and demonstrate the short-term stability of fresh or thawed products, as well their stability during long-term storage. Detailed results of media simulation tests, validation runs and early MSC batches are presented. We also report the validation of a new variant of the process aiming to prepare fresh MSCs for the treatment of specific lesions of Crohn’s disease by local injection. In conclusion, we have successfully ensured the adaptation of our clinical-grade MSC production process to the GMP requirements. The GMP manufacturing of MSC products is feasible in the academic setting for a limited number of batches with a significant cost increase, but moving to large-scale production necessary for phase III trials would require the involvement of industrial partners.

Exploratory assessment of the current EU regulatory framework for development of advanced therapies

1969 ◽  
Vol 16 (4) ◽  
Author(s):  
Pawanbir Singh ◽  
Laure Brévignon-Dodin ◽  
Satya P Dash
Keyword(s):  
Regenerative Medicine ◽  
Research And Development ◽  
Regulatory Framework ◽  
Medicinal Products ◽  
Advanced Therapy Medicinal Products ◽  
Regulatory Strategy ◽  
Technology Changes ◽  
Advanced Therapy ◽  
Advanced Therapies ◽  
The Eu

The Advanced Therapy Medicinal Products (ATMP) Regulation provides a necessary regulatory framework for the commercialisation and use of regenerative medicine-based therapeutic products in the EU. However, concerns have been raised about the appropriateness of the regulatory strategy it has adopted to address different, complex and evolving categories of medicinal products. This article explores some of the potential shortfalls of the ATMP Regulation with regard to facilitating the research and development of advanced therapies in the present and in the future. It concludes that while providing a much needed harmonised regulatory framework for the companies operating in the sector, the new regulation has yet to demonstrate its capacity to keep up with radical technology changes.

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 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.

Sign in / Sign up

Export Citation Format

Share Document