Inter-center comparison of good manufacturing practices-compliant stromal vascular fraction and proposal for release acceptance criteria: a review of 364 productions

• Published in: Stem cell research & therapy Vol. 12; no. 1; pp. 1 - 373
• Main Authors: François, Pauline, Rusconi, Giulio, Arnaud, Laurent, Mariotta, Luca, Giraudo, Laurent, Minonzio, Greta, Veran, Julie, Bertrand, Baptiste, Dumoulin, Chloé, Grimaud, Fanny, Lyonnet, Luc, Casanova, Dominique, Giverne, Camille, Cras, Audrey, Magalon, Guy, Dignat-George, Françoise, Sabatier, Florence, Magalon, Jeremy, Soldati, Gianni
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 01.07.2021; BioMed Central; BMC
• Subjects: Adipose tissue; Advanced therapy medicinal product; Antibodies; Automation; Cell subset distribution; Cell viability; Clinical trials; Comparative analysis; Endothelial cells; Environmental monitoring; Flow cytometry; France; Gating; GMP production; Good Manufacturing Practice; Hospitals; Leukocytes; Manufacturing; Microbiology; Pericytes; Stem cells; Stromal cells; Stromal vascular fraction; France; United States > US; Switzerland
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-021-02445-z

Background Even though the manufacturing processes of the stromal vascular fraction for clinical use are performed in compliance with the good manufacturing practices applying to advanced therapy medicinal products, specifications related to stromal vascular fraction quality remain poorly defined. We analyzed stromal vascular fraction clinical batches from two independent good manufacturing practices-compliant manufacturing facilities, the Swiss Stem Cell Foundation (SSCF) and Marseille University Hospitals (AP-HM), with the goal of defining appropriate and harmonized release acceptance criteria. Methods This retrospective analysis reviewed the biological characteristics of 364 batches of clinical-grade stromal vascular fraction. Collected data included cell viability, recovery yield, cell subset distribution of stromal vascular fraction, and microbiological quality. Results Stromal vascular fraction from SSCF cohort demonstrated a higher viability (89.33% [+ or -] 4.30%) and recovery yield (2.54 x 10.sup.5 [+ or -] 1.22 x 10.sup.5 viable nucleated cells (VNCs) per mL of adipose tissue) than stromal vascular fraction from AP-HM (84.20% [+ or -] 5.96% and 2.25 x 10.sup.5 [+ or -] 1.11 x 10.sup.5 VNCs per mL). AP-HM batches were significantly less contaminated (95.71% of sterile batches versus 74.15% for SSCF batches). The cell subset distribution was significantly different (higher proportion of endothelial cells and lower proportion of leukocytes and pericytes in SSCF cohort). Conclusions Both centers agreed that a good manufacturing practices-compliant stromal vascular fraction batch should exert a viability equal or superior to 80%, a minimum recovery yield of 1.50 x 10.sup.5 VNCs per mL of adipose tissue, a proportion of adipose-derived stromal cells at least equal to 20%, and a proportion of leukocytes under 50%. In addition, a multiparameter gating strategy for stromal vascular fraction analysis is proposed. Keywords: Stromal vascular fraction, Adipose tissue, Cell subset distribution, Flow cytometry, GMP production, Advanced therapy medicinal product