AN OVERVIEW OF THE PLX MANUFACTURING PROCESS, HIGHLIGHTING FOUNDATION ELEMENTS FOR SMART SCALING

In order to design a cell manufacturing process capable of meeting marketing-level outputs under cGMP conditions, it is useful to keep several guiding elements in mind: closed systems, automation/streamlining, scalability, and environmental control. Here we present an overview of Pluristem Therapeutics’ PLX manufacturing process to illustrate how these elements were implemented. The first stage of the process is 2D cell expansion following placental isolation; this expansion is performed in a closed multi-tray system. Cells are then further expanded in perfused-bed bioreactors which utilize a scalable microcarrier platform in a growth environment tightly controlled by an automated control platform. After harvest, cells are concentrated and washed via a closed, aseptic continuous centrifugation technology which can process multiple cycles, each containing tens of billions of cells. After concentration and washing, cells are formulated to their correct final concentration, mixed with cryopreservation solution, and filled into vials - all within a closed, semi-automated spinner flask and filling kit.