Abstract 14 Omidubicel-Onlv: Robustness of the Manufacturing Process

INTRODUCTION: Omidubicel-onlv is a nicotinamide (NAM) -modified allogeneic hematopoietic progenitor cell therapy derived from cord blood. NAM expansion increases the number of stem and progenitor cells, inhibits differentiation, and potentiates migration, bone marrow homing, and engraftment efficiency. A global phase 3 trial demonstrated faster hematopoietic recovery, reduced rates of infection, and shorter hospitalizations for patients randomized to omidubicel-onlv compared to standard umbilical cord blood (UCB). Omidubicel-onlv is manufactured for each patient from a single, appropriately matched cord blood unit (CBU). The inherent donor variability as well as the different processing and testing methods used by different Cord Blood Banks (CBBs) present challenges in maintaining a consistent product. OBJECTIVES: This extensive study was conducted to confirm the robustness of the manufacturing process and the proven acceptable range for the critical and key process parameters. METHODS: Seven process parameters were evaluated in total. Of these, three parameters were related to the CD34+ expansion phase: CD34+ seeding concentration, incubation temperature, and CO(2) levels. Four additional parameters were related to final product formulation and cryopreservation: hold times during harvest and formulation, cell concentration in the drug product, DMSO concentration, and storage temperature. The impact of each process parameter on product performance was assessed by a side-by-side comparison of its target value (control) versus the tested range. Each parameter was evaluated using at least three batches derived from three CBUs. Statistical analysis of the coefficient of variation or recovery against the control was applied to the data sets. RESULTS: Statistical analyses demonstrated an overall variability of ≤30% in critical attributes including fold expansion, viability, phenotyping, and recovery of cells post-cryopreservation and stability. DISCUSSION: The omidubicel-onlv manufacturing process is robust, overcoming the variability of batches derived from different donors, different processing and testing methods at CBBs, and manufacturing process parameters.