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

Abstract 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 % ± 4.30 %) and recovery yield (2.54 × 105 ± 1.22 × 105 viable nucleated cells (VNCs) per mL of adipose tissue) than stromal vascular fraction from AP-HM (84.20% ± 5.96% and 2.25 × 105 ± 1.11 × 105 VNCs). AP-HM batches were significantly less contaminated (95.71 % of sterile batches versus 74.15 %) 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 × 105 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 analyze is proposed.