Patrick Wuchter1, Karen Bieback2, Hubert Schrezenmeier3, Martin Bornhäuser4, Lutz P Müller5, Halvard Bönig6, Wolfgang Wagner7, Roland Meisel8, Petra Pavel9, Torsten Tonn10, Peter Lang11, Ingo Müller12, Matthias Renner13, Georg Malcherek14, Rainer Saffrich14, Eike C Buss14, Patrick Horn14, Markus Rojewski3, Anita Schmitt14, Anthony D Ho14, Ralf Sanzenbacher13, Michael Schmitt14. 1. Department of Medicine V, Heidelberg University, Heidelberg, Germany. Electronic address: patrick.wuchter@med.uni-heidelberg.de. 2. Institute of Transfusion Medicine and Immunology Mannheim, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Donor Service Baden-Württemberg-Hessen, Mannheim, Germany. 3. Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University of Ulm, Ulm, Germany. 4. Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany. 5. Department of Medicine IV, University Hospital Halle (Saale), Halle (Saale), Germany. 6. Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt/Main and German Red Cross Blood Service Baden-Württemberg-Hessen, Frankfurt/Main, Germany. 7. Helmholtz Institute for Biomedical Technology, Stem Cell Biology and Cellular Engineering, University of Aachen Medical School, Aachen, Germany. 8. Division of Pediatric Stem Cell Therapy, Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany. 9. Stem Cell Laboratory, IKTZ Heidelberg GmbH, Heidelberg, Germany. 10. Institute of Transfusion Medicine, Red Cross Blood Transfusion Service Dresden, Dresden, Germany. 11. Department of Pediatrics, University Clinic Tübingen, Tübingen, Germany. 12. Clinic for Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 13. Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany. 14. Department of Medicine V, Heidelberg University, Heidelberg, Germany.
Abstract
BACKGROUND AIMS: Human mesenchymal stem or stromal cells (MSCs) represent a potential resource not only for regenerative medicine but also for immunomodulatory cell therapies. The application of different MSC culture protocols has significantly hampered the comparability of experimental and clinical data from different laboratories and has posed a major obstacle for multicenter clinical trials. Manufacturing of cell products for clinical application in the European Community must be conducted in compliance with Good Manufacturing Practice and requires a manufacturing license. In Germany, the Paul-Ehrlich-Institut as the Federal Authority for Vaccines and Biomedicines is critically involved in the approval process. METHODS: This report summarizes a consensus meeting between researchers, clinicians and regulatory experts on standard quality requirements for MSC production. RESULTS: The strategy for quality control testing depends on the product's cell composition, the manufacturing process and the indication and target patient population. Important quality criteria in this sense are, among others, the immunophenotype of the cells, composition of the culture medium and the risk for malignant transformation, as well as aging and the immunosuppressive potential of the manufactured MSCs. CONCLUSIONS: This position paper intends to provide relevant information to interested parties regarding these criteria to foster the development of scientifically valid and harmonized quality standards and to support approval of MSC-based investigational medicinal products.
BACKGROUND AIMS: Human mesenchymal stem or stromal cells (MSCs) represent a potential resource not only for regenerative medicine but also for immunomodulatory cell therapies. The application of different MSC culture protocols has significantly hampered the comparability of experimental and clinical data from different laboratories and has posed a major obstacle for multicenter clinical trials. Manufacturing of cell products for clinical application in the European Community must be conducted in compliance with Good Manufacturing Practice and requires a manufacturing license. In Germany, the Paul-Ehrlich-Institut as the Federal Authority for Vaccines and Biomedicines is critically involved in the approval process. METHODS: This report summarizes a consensus meeting between researchers, clinicians and regulatory experts on standard quality requirements for MSC production. RESULTS: The strategy for quality control testing depends on the product's cell composition, the manufacturing process and the indication and target patient population. Important quality criteria in this sense are, among others, the immunophenotype of the cells, composition of the culture medium and the risk for malignant transformation, as well as aging and the immunosuppressive potential of the manufactured MSCs. CONCLUSIONS: This position paper intends to provide relevant information to interested parties regarding these criteria to foster the development of scientifically valid and harmonized quality standards and to support approval of MSC-based investigational medicinal products.
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