Compliance with good manufacturing practice in the assessment of immunomodulation potential of clinical grade multipotent mesenchymal stromal Cells Derived from Wharton's Jelly
Grau-Vorster, Marta (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rodríguez, Luciano (Banc de Sang i Teixits)
del Mazo-Barbara, Anna (Banc de Sang i Teixits)
Mirabel, Clémentine (Banc de Sang i Teixits)
Blanco, Margarita (Banc de Sang i Teixits)
Codinach, Margarita (Banc de Sang i Teixits)
G. Gómez, Susana (Banc de Sang i Teixits)
Querol, Sergi (Banc de Sang i Teixits)
García López, Joan (Banc de Sang i Teixits)
Vives Armengol, Joaquim (Banc de Sang i Teixits)

Fecha:	2019
Resumen:	The selection of assays suitable for testing the potency of clinical grade multipotent mesenchymal stromal cell (MSC)-based products and its interpretation is a challenge for both developers and regulators. Here, we present a bioprocess design for the production of Wharton's jelly (WJ)-derived MSCs and a validated immunopotency assay approved by the competent regulatory authority for batch release together with the study of failure modes in the bioprocess with potential impact on critical quality attributes (CQA) of the final product. Methods: The lymphocyte proliferation assay was used for determining the immunopotency of WJ-MSCs and validated under good manufacturing practices (GMP). Moreover, failure mode effects analysis (FMEA) was used to identify and quantify the potential impact of different unexpected situations on the CQA. Results: A production process based on a two-tiered cell banking strategy resulted in batches with sufficient numbers of cells for clinical use in compliance with approved specifications including MSC identity (expressing CD73, CD90, CD105, but not CD31, CD45, or HLA-DR). Remarkably, all batches showed high capacity to inhibit the proliferation of activated lymphocytes. Moreover, implementation of risk management tools led to an in-depth understanding of the manufacturing process as well as the identification of weak points to be reinforced. Conclusions: The bioprocess design showed here together with detailed risk management and the use of a robust method for immunomodulation potency testing allowed for the robust production of clinical-grade WJ-MSCs under pharmaceutical standards.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Multipotent mesenchymal stromal cell ; Immunomodulation ; Proliferation assay ; Cellular ; Therapy ; Cell culture ; Good manufacturing practice ; Quality by design
Publicado en:	Cells, Vol. 8 (2019) , p. 1-13, ISSN 2073-4409

DOI: 10.3390/cells8050484
PMID: 31117301

13 p, 3.0 MB

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