Standardization of Good Manufacturing Practice–compliant production of bone marrow–derived human mesenchymal stromal cells for immunotherapeutic applications

Wuchter, Patrick; Bieback, Karen; Schrezenmeier, Hubert; Bornhäuser, Martin; Müller, Lutz; Bönig, Halvard; Wagner, Wolfgang; Meisel, Roland; Pavel, Petra; Tonn, Torsten; Lang, Peter; Müller, Ingo; Renner, Matthias; Malcherek, Georg; Saffrich, Rainer; Buss, Eike C.; Horn, Patrick; Rojewski, Markus; Schmitt, Anita; Ho, Anthony D.; Sanzenbacher, Ralf; Schmitt, Michael

doi:10.1016/j.jcyt.2014.04.002

Cited by 131 publications

(119 citation statements)

References 110 publications

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“…As the recent work of a group of German researchers pointed out the manufacturing and quality control issues [13], we hope that our work could be a significant first step forward the awareness of the Regulatory Authority that a wider agreement on this matter is the needing. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction.…”

Section: Resultsmentioning

confidence: 84%

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Ex Vivo Expanded Mesenchymal Stromal Cell Minimal Quality Requirements for Clinical Application

Torre

Lucarelli

GuidiSimona³

et al. 2015

Stem Cells and Development

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Mesenchymal Stromal Cells (MSC), as advanced therapy products, must satisfy all the requirements for human use of medicinal products, aiming to maintain the quality and safety of the cells. The MSC manufacturing process for clinical use should comply with the principles of Good Manufacturing Practice (GMP). This ensures that cell preparations are produced and controlled, from the collection and manipulation of raw materials, through the processing of intermediate products, to the quality controls, storage, labelling and packaging, and release.The objective of this document is to provide the minimal quality requirements for the MSC production and its delivery for clinical use, so the safety of the final cell therapy product will not be compromised. For this purpose, the document evaluates the most important steps of GMP-compliant MSC production: the isolation and expansion process; the validation phase of the process, including all quality controls for the characterization, functionality, potency and safety of MSCs; the quality control at the batch release to guarantee the safety of patient infusion. This opinion paper reflects the consensus viewpoint of the authors and scientists participating the GISM Working Group*.

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Section: Resultsmentioning

confidence: 84%

“…Manufacturing and quality control issues are frequently under discussion during the regulatory authorization processes. The recent paper of Wuchter summarizes a consensus meeting between researchers, clinicians and regulatory experts on standard quality requirements for MSC production [13].…”

Section: Patientmentioning

confidence: 99%

Ex Vivo Expanded Mesenchymal Stromal Cell Minimal Quality Requirements for Clinical Application

Torre

Lucarelli

GuidiSimona³

et al. 2015

Stem Cells and Development

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show abstract

“…New technologies for epigenetic analyses of cells could provide important information regarding the classification of types [46] based on their tissue of origin even after extensive culture, and about bioprocessing during differentiation of MSCs and its impact on epigenetic patterns [47]. The generation of specific epigenetic signatures reflects functional properties of MSCs such as their hematopoiesis supportive function [48]. Epigenetic signatures could be also developed in order to evaluate the therapeutic potential of MSCs after validation with suitable datasets.…”

Section: On Quality Control and Product Comparabilitymentioning

confidence: 99%

Bioprocess engineering strategies for autologous human MSC-based therapies: one size does not fit all

Papantoniou¹,

Lambrechts²,

Aerts³

2017

Cell Gene Therapy Insights

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“…Also included in the ISCT definition is the adherence to plastic surfaces and the differentiation capacity in vitro into osteoblasts, adipocytes and chondroblasts. These characteristics must be defined and extended specifically for each cell line depending on its source [19].…”

Section: Cells As a Productmentioning

confidence: 99%

The Challenge of Human Mesenchymal Stromal Cell Expansion: Current and Prospective Answers

Elseberg¹,

Leber²,

Weidner³

et al. 2017

New Insights Into Cell Culture Technology

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In the field of cell therapy, allogenic human mesenchymal stromal cells (hMSCs) are often used in clinical trials, creating a demand for cell mass production using efficient dynamic bioreactor systems. As an advanced therapy medicinal product (ATMP), such cells should meet certain special requirements, including product specifications requiring a production process compatible with good manufacturing practice (GMP). The development of processes in which the cells are the product therefore remains a significant challenge. This chapter describes the requirements at different steps in the upstream and downstream phases of such dynamic processes. Potential solutions are presented and future prospects are discussed, including the selection of media and carriers for the strictly adherent growing cells, allowing efficient cell adhesion and detachment. Strategies for dynamic cultivation in bioreactors are described in detail for fixed-bed and stirred-tank reactors based on GMP requirements and the integration of process analytical technology (PAT). Following cell harvest, separation and purification, the formulation and storage of the product are also described. Finally, the chapter covers important cell quality characteristics necessary for the approval of ATMPs.

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Standardization of Good Manufacturing Practice–compliant production of bone marrow–derived human mesenchymal stromal cells for immunotherapeutic applications

Cited by 131 publications

References 110 publications

Ex Vivo Expanded Mesenchymal Stromal Cell Minimal Quality Requirements for Clinical Application

Ex Vivo Expanded Mesenchymal Stromal Cell Minimal Quality Requirements for Clinical Application

Bioprocess engineering strategies for autologous human MSC-based therapies: one size does not fit all

The Challenge of Human Mesenchymal Stromal Cell Expansion: Current and Prospective Answers

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