Principal Criteria for Evaluating the Quality, Safety and Efficacy of hMSC-Based Products in Clinical Practice: Current Approaches and Challenges
Abstract
:1. Introduction
2. Design of an hMSC-Based Product Manufacturing Process
2.1. Donor Selection and Serology
2.2. Isolation and Processing of hMSCs
2.3. Characterization of hMSCs
2.4. Cryopreservation of hMSCs
2.5. hMSC-Based Product Packaging
2.6. Release of hMSC-Based Products
3. Minimal Criteria for hMSC Characterization
3.1. Identity
3.2. Viability
3.3. Purity
3.3.1. Cell Impurities
3.3.2. Process Impurities
3.4. Potency
3.5. Proliferative Capacity
3.6. Genomic Stability
3.7. Microbiological Quality Control
3.7.1. Sterility Test
3.7.2. Mycoplasma
3.7.3. Adventitious Viruses
3.8. Tumorigenicity
3.9. Efficacy
4. Conclusions and Future Perspectives
Funding
Acknowledgments
Conflicts of Interest
References
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Cell Characterization Criteria | Assays | Methods | Release Criteria | According to Different Frameworks | |
---|---|---|---|---|---|
FDA | EMA | ||||
Identity | Morphology | Microscopy |
| N/A | N/A |
Phenotypic markers | Flow cytometry, FACS analysis |
| N/A | N/A | |
Ability to differentiate | Stain | Differentiate into osteoblasts, adipocytes or chondroblasts | N/A | N/A | |
Purity | Endotoxin detection | LAL test | ≤0.5 EU/ml | ICH Guideline Q4B Annex 14 | |
|
| ||||
Potency | Paracrine secretion (cytokines) |
|
| ICH Q6B | |
|
| ||||
Viability | Living/dead cell count |
|
|
|
|
Proliferative capacity | Total cumulative population doubling | Total number of cellular divisions | No senescence | N/A | N/A |
Genomic stability | Karyotype |
(at least 20metaphases) |
| N/A | N/A |
Microbiological quality control | Sterility test | Direct inoculation | Negative (no haze in the media) | ICH guideline Q4B Annex 8 | |
|
| ||||
Mycoplasma test | Real-time PCR | Negative |
|
| |
Adventitious viruses (for allogeneic products) | In vitro adventitious viral agent test | Negative | ICH Topic Q 5 A (R1) | ||
|
|
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Guadix, J.A.; López-Beas, J.; Clares, B.; Soriano-Ruiz, J.L.; Zugaza, J.L.; Gálvez-Martín, P. Principal Criteria for Evaluating the Quality, Safety and Efficacy of hMSC-Based Products in Clinical Practice: Current Approaches and Challenges. Pharmaceutics 2019, 11, 552. https://doi.org/10.3390/pharmaceutics11110552
Guadix JA, López-Beas J, Clares B, Soriano-Ruiz JL, Zugaza JL, Gálvez-Martín P. Principal Criteria for Evaluating the Quality, Safety and Efficacy of hMSC-Based Products in Clinical Practice: Current Approaches and Challenges. Pharmaceutics. 2019; 11(11):552. https://doi.org/10.3390/pharmaceutics11110552
Chicago/Turabian StyleGuadix, Juan Antonio, Javier López-Beas, Beatriz Clares, José Luis Soriano-Ruiz, José Luis Zugaza, and Patricia Gálvez-Martín. 2019. "Principal Criteria for Evaluating the Quality, Safety and Efficacy of hMSC-Based Products in Clinical Practice: Current Approaches and Challenges" Pharmaceutics 11, no. 11: 552. https://doi.org/10.3390/pharmaceutics11110552