Development of a cell-based medicinal product: regulatory structures in the European Union

Gálvez, Patrícia; Clares, Beatriz; Hmadcha, Abdelkrim; Ruiz, Adolfina; Soria, Bernat

doi:10.1093/bmb/lds036

Cited by 44 publications

(32 citation statements)

References 29 publications

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“…In the definition of MSC-based therapies cell production and application have been the object of extensive clinical and pre-clinical research 2 , with particular attention to specific international regulation for the safety and efficacy of cell based medicinal product (CBMP) treatments 3 . Human MSCs are extensively cultured in media containing supplements and reagents of animal origin, such as fetal bovine serum (FBS) and bovine trypsin.…”

Section: Introductionmentioning

confidence: 99%

Isolating Mesangiogenic Progenitor Cells (MPCs) from Human Bone Marrow

Montali

Barachini

Pacini

et al. 2016

JoVE

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In a research study aimed to isolate human bone marrow (hBM)-derived Mesenchymal Stromal Cells (MSCs) for clinical applications, we identified a novel cell population specifically selected for growth in human serum supplemented medium. These cells are characterized by morphological, phenotypic, and molecular features distinct from MSCs and we named them Mesodermal Progenitor Cells (MPCs). MPCs are round, with a thick highly refringent core region; they show strong, trypsin resistant adherence to plastic. Failure to expand MPCs directly revealed that they are slow in cycling. This is as also suggested by Ki-67 negativity. On the other hand, culturing MPCs in standard medium designed for MSC expansion, gave rise to a population of exponentially growing MSC-like cells. Besides showing mesenchymal differentiation capacity MPCs retained angiogenic potential, confirming their multiple lineage progenitor nature. Here we describe an optimized highly reproducible protocol to isolate and characterize hBM-MPCs by flow cytometry (CD73, CD90, CD31, and CD45), nestin expression, and F-actin organization. Protocols for mesengenic and angiogenic differentiation of MPCs are also provided. Here we also suggest a more appropriate nomenclature for these cells, which has been re-named as "Mesangiogenic Progenitor Cells".

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Section: Introductionmentioning

confidence: 99%

Isolating Mesangiogenic Progenitor Cells (MPCs) from Human Bone Marrow

Montali

Barachini

Pacini

et al. 2016

JoVE

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“…It should be noted that the clinical use of living cells in advanced therapy and regenerative medicine has to be carried out under the GMP standards, which imply that for any development of a skin substitute with living cells, a manufacturing protocol and programme of quality control have to be previously defined and validated. 86 The quality controls include the following: (i) the biological characterization of the cellular component (identity, viability, dose, purity, potency, karyotype and tumourigenicity); (ii) the microbiological quality of the product (sterility, mycoplasma detection, pyrogen and endotoxins testing and adventitious viruses); and (iii) the environment quality control where the substitute is manufactured (surfaces, air, personnel and facilities). 87 Despite the substantial progress made in clinical assays, it remains a great challenge to produce a precise and complex new tissue that mimics the native skin by including several cell types arranged in a specific 3D pattern.…”

Section: Current and Future Clinical Applicationsmentioning

confidence: 99%

Therapeutic strategies for skin regeneration based on biomedical substitutes

Chocarro‐Wrona

López‐Ruiz

Perán

et al. 2019

Acad Dermatol Venereol

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Regenerative medicine and tissue engineering (TE) have experienced significant advances in the development of in vitro engineered skin substitutes, either for replacement of lost tissue in skin injuries or for the generation of in vitro human skin models to research. However, currently available skin substitutes present different limitations such as expensive costs, abnormal skin microstructure and engraftment failure. Given these limitations, new technologies, based on advanced therapies and regenerative medicine, have been applied to develop skin substitutes with several pharmaceutical applications that include injectable cell suspensions, cell‐spray devices, sheets or 3Dscaffolds for skin tissue regeneration and others. Clinical practice for skin injuries has evolved to incorporate these innovative applications to facilitate wound healing, improve the barrier function of the skin, prevent infections, manage pain and even to ameliorate long‐term aesthetic results. In this article, we review current commercially available skin substitutes for clinical use, as well as the latest advances in biomedical and pharmaceutical applications used to design advanced therapies and medical products for wound healing and skin regeneration. We highlight the current progress in clinical trials for wound healing as well as the new technologies that are being developed and hold the potential to generate skin substitutes such as 3D bioprinting‐based strategies.

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“…This is a paradigm change in regulation, posing new riddles around Good Manufacturing Practice (GMP), requiring new standards for quality, potency and safety, as well as process design and assurance strategies (5). With individual batches essentially corresponding to a different product, ATMPs also face unique challenges in product standardization, including inspection and release testing (6).…”

Section: Uncharted Waters: Canvassing Unique and Persisting Bottlenecksmentioning

confidence: 99%

Adaptation through Collaboration: Developing Novel Platforms to Advance the Delivery of Advanced Therapies to Patients

Papadaki

2017

Front. Med.

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For the nascent field of advanced therapies, collaboration will be a game-changer, turning scientific progress that was once unimaginable into transformative medical practice. Despite promise for lifelong management and even cure of disease, skepticism remains about the feasibility of their delivery to patients, fueling investment risks. With the potential for long-term effectiveness in need of frequent reassessment, current approaches to predict real-life drug performance bear little relevance, necessitating novel and iterative schemes to monitoring the benefit–risk profiles throughout the life span of advanced therapies. This work explains that reinventing an adoption route for Advanced Therapy Medicinal Products is as much about the scientific and clinical components, as it is about the organizational structures, requiring an unprecedented level of interactions between stakeholders not traditionally connected; from developers and regulators, to payers, patients, and funders. By reflecting on the successes and lessons learned from the growing space of global precompetitive consortia and public–private partnerships, as well as a number of emerging accelerated development pathways, this work aims to inform the foundations for a future roadmap that can smooth the path to approval, reimbursement, and access, while delivering value to all stakeholders. Echoing the growing demands to bring these transformative products to patients, it provides critical insights to enhance our capacity in three fundamental domains: deploying the operational flexibilities offered by the growing space of collaborations, utilizing emerging flexible and accelerated pathways to tackle challenges in quantifying long-term effectiveness, and building the necessary digital and clinical infrastructure for knowledge development.

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Development of a cell-based medicinal product: regulatory structures in the European Union

Abstract: The development of cell therapy medicinal products constitutes an alternative therapeutic strategy to conventional clinical therapy, for which no effective cure was previously available.

Cited by 44 publications

References 29 publications

Isolating Mesangiogenic Progenitor Cells (MPCs) from Human Bone Marrow

Isolating Mesangiogenic Progenitor Cells (MPCs) from Human Bone Marrow

Therapeutic strategies for skin regeneration based on biomedical substitutes

Adaptation through Collaboration: Developing Novel Platforms to Advance the Delivery of Advanced Therapies to Patients

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