Background: Column chromatography is an important technique in monoclonal antibody purification processes. The performance of columns is a critical factor for product quality and process yields. Each column pack must be qualified for use and monitored throughout its lifetime to ensure optimal performance however current testing methods require taking the column offline and lack sensitivity to significant changes in the column pack. Objective: Transition analysis was implemented as a PAT tool to evaluate process data and provide real-time column monitoring for a commercial monoclonal antibody downstream process. This PAT tool is also currently being implemented across the Janssen network for multiple products at clinical and commercial scale. Method: This PAT tool uses a mathematical model to fit a curve through mobile phase transition data generated during chromatography processing. Model curve parameters are utilized to calculate HETP as a measure of flow dispersion across the column bed as an indicator of column performance. Results: The automatic PAT tool has been fully implemented for all four chromatography steps in Janssen’s Malvern PA manufacturing site, resulting in significant improvements in process yield and more efficient and reliable operation. Implementation is currently underway across the Janssen large molecule platform, including BioCork, Ireland, where recent results show suitability for purification processes at both clinical and commercial scale. Real life case studies show broad applicability for use of the PAT tool. Greater sensitivity to changes in column performance over time is possible because of a good fit between the model and process data. Several case studies are presented showing correlations between yield and HETP which helped identify and correct causes of column degradation over time. This resulted in a more stable column pack, performing better with increased protein recovery. Conclusions: An automated PAT tool has been successfully qualified and implemented, providing real time performance analysis during commercial large molecule purification process with comparison to statistical process control limits derived from historical production data. Implementation of this inline analysis tool is planned across the Janssen network to achieve the potential of enhanced column performance and resultant improvements to protein yield.

Transition analysis: Real-time column performance monitoring in commercial scale chromatography

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.