Biotech Diafiltration Process Optimization and Control Using Six Sigma Methods

Abstract

Abstract — Biologics parenteral downstream protein purification process often requires a buffer exchanges step. This process can be described also as a product washing step. In order to optimize a protein DF process is important to know what process initial conditions have a major effect on the process CTQ (critical to quality) attributes. For this case these attributes are; DF process pH, osmolality and conductivity. The main objective of this project was the optimization of Product X DF diafiltration process based on process factors Buffer and product initial conductivity, because these factors were found variable during several runs. A Six Sigma methodology was implemented in order to identify, how the factors initial conditions can be modify to optimize the DF operation. To identify which factor has the major effect on the DF process DMAIC, DOE, full Factorial Design 2^k experiment was used. Finally, experiments results, demonstrated that the DF buffer initial conductivity has the major effect on process final CTQ’s. In addition, it was concluded that a formulation buffer initial conductivity of 13.5 mS/cm will result in a cost and cycle time reduction of 50 %, while DF process CTQ’s are maintained under the specification limits. Key Terms — Biotech Process, Buffer Conductivity, Critical to Quality, Diafiltration