Characterization of Monoclonal Antibody Primary Recovery and Purification Steps: Towards Process Validation

This paper will focus on summarizing the approaches taken to characterize a monoclonal antibody downstream process including primary recovery and purification steps. Utilization of Failure Mode and Effect Analysis (FMEA) and experimental approaches to efficiently characterize primary recovery (centrifugation, depth filtration and ultrafiltration) and purification steps (chromatography) are presented. The important parameters (based on severity, occurrence and detection) were determined as a result of FMEA. In addition to probe experiments, design of experiment (DOE) methods were utilized where possible to increase the efficiency of experimentation and to make statistical analysis possible. As a result, the parameters were categorized into key, critical or non-key classes. The ranges identified were checked and process robustness was demonstrated via purification of off-center cell culture batches.