MSC Manufacturing for Academic Clinical Trials: From a Clinical-Grade to a Full GMP-Compliant Process
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 obtai...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/6/1320 |
| _version_ | 1797532643787538432 |
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| author | Chantal Lechanteur Alexandra Briquet Virginie Bettonville Etienne Baudoux Yves Beguin |
| author_facet | Chantal Lechanteur Alexandra Briquet Virginie Bettonville Etienne Baudoux Yves Beguin |
| author_sort | Chantal Lechanteur |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T11:02:12Z |
| format | Article |
| id | doaj.art-2450de3cbc9a4131b422c110a7f09fbe |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T11:02:12Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2450de3cbc9a4131b422c110a7f09fbe2023-11-21T21:23:35ZengMDPI AGCells2073-44092021-05-01106132010.3390/cells10061320MSC Manufacturing for Academic Clinical Trials: From a Clinical-Grade to a Full GMP-Compliant ProcessChantal Lechanteur0Alexandra Briquet1Virginie Bettonville2Etienne Baudoux3Yves Beguin4Laboratory of Cell and Gene Therapy, Department of Hematology, CHU of Liège, 4000 Liège, BelgiumLaboratory of Cell and Gene Therapy, Department of Hematology, CHU of Liège, 4000 Liège, BelgiumLaboratory of Cell and Gene Therapy, Department of Hematology, CHU of Liège, 4000 Liège, BelgiumLaboratory of Cell and Gene Therapy, Department of Hematology, CHU of Liège, 4000 Liège, BelgiumLaboratory of Cell and Gene Therapy, Department of Hematology, CHU of Liège, 4000 Liège, BelgiumFollowing 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.https://www.mdpi.com/2073-4409/10/6/1320cell therapyMSCGMPATMP manufacturingmesenchymal stromal cells |
| spellingShingle | Chantal Lechanteur Alexandra Briquet Virginie Bettonville Etienne Baudoux Yves Beguin MSC Manufacturing for Academic Clinical Trials: From a Clinical-Grade to a Full GMP-Compliant Process Cells cell therapy MSC GMP ATMP manufacturing mesenchymal stromal cells |
| title | MSC Manufacturing for Academic Clinical Trials: From a Clinical-Grade to a Full GMP-Compliant Process |
| title_full | MSC Manufacturing for Academic Clinical Trials: From a Clinical-Grade to a Full GMP-Compliant Process |
| title_fullStr | MSC Manufacturing for Academic Clinical Trials: From a Clinical-Grade to a Full GMP-Compliant Process |
| title_full_unstemmed | MSC Manufacturing for Academic Clinical Trials: From a Clinical-Grade to a Full GMP-Compliant Process |
| title_short | MSC Manufacturing for Academic Clinical Trials: From a Clinical-Grade to a Full GMP-Compliant Process |
| title_sort | msc manufacturing for academic clinical trials from a clinical grade to a full gmp compliant process |
| topic | cell therapy MSC GMP ATMP manufacturing mesenchymal stromal cells |
| url | https://www.mdpi.com/2073-4409/10/6/1320 |
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