(47b) Characterization Of Downstream Processing Steps Used In The Purification Of A Monoclonal Antibody

This paper will focus on utilization of Failure Mode and Effect Analysis (FMEA) and Design of Experiments (DOE) methods to characterize downstream processing steps for purification of a monoclonal antibody. Once the important parameters (based on severity, occurrence and detection) were determined as a result of FMEA, these parameters and operating ranges for a robust process were determined either by full factorial or central composite design. For the Protein A step, elution pH had an affect on DNA content and turbidity of the product. For the cation exchange step, many of the parameters, such as elution buffer pH and conductivity, had an impact on the final product purity (such as aggregate content) and yield of the step. Based on the findings, parameters were classified and ranges were identified to yield a robust process.