Definition of a platform continuous capture scale down model and link to scale-up for monoclonal antibody clinical manufacturing
October 6-10, 2019
Definition and scale-up of a batch chromatography process is based on a few main variables such as linear velocity, column loading, and bed height, which are scaled proportionally to column volume. Continuous chromatography consists of multiple columns with column loading and washes/elution/regeneration occurring simultaneously. The definition of a small scale method for continuous chromatography can be extremely complex due to the extensive number of method variables. Limited knowledge exists for development of a scale down and up strategy for continuous chromatography. This abstract should provide some insight into case studies on integration of continuous operations and scale-up, which is one of the themes of the integrated continuous biomanufacturing (ICB) conference.
This presentation will describe a strategy for definition of a platform continuous capture scale down model and scale-up pathway. The platform continuous capture step utilizes periodic counter-current chromatography (PCC) for operation of affinity chromatography in a semi-continuous manner. A scale down model for the PCC step was defined and simplified to the following three ranges of harvested cell culture fluid (HCCF) titers: ≤ 2 g/L, 2.5-8 g/L, and 8.5-13 g/L. For each of the three titer ranges, the following variable setpoints are changed based on the specific HCCF titer range: step linear velocity, number of columns, column size, and ΔUV. After these setpoints are inputted into the algorithm, PCC method variables, such as sample loading flowrate, loop time, number of loops and cycles, throughput (g/L/hr), and time cycle, will populate to finish the method design.
This PCC scale down model was utilized to scale-up to a bioreactor range of 500-2000L. Quality results showed a good correlation between scale down model and scale-up data. Additional parameters for the 2000L scale-up run included assessment of cleaning and drug substance stability. The cleaning results of the continuous chromatography skid showed passing bioburden, endotoxin, and conductivity. Drug substance stability was also maintained for a year, which was the study duration. This data set proves the PCC small scale model data is representative of the scale-up quality results. In addition, targets such as skid cleanability and DS stability met specifications, which supports the scale-up package for implementation of a platform continuous capture step into a purification process for clinical mAb manufacturing.
Rebecca A. Chmielowski, Matt Kessler, Collette Cutler, Hong Li, and David Roush, "Definition of a platform continuous capture scale down model and link to scale-up for monoclonal antibody clinical manufacturing" in "Integrated Continuous Biomanufacturing IV", Veena Warikoo, Roche, USA Alois Jungbauer, BOKU, Austria Jon Coffman, Boehringer Ingelheim, USA Jason Walther, Sanofi, USA Eds, ECI Symposium Series, (2019). https://dc.engconfintl.org/biomanufact_iv/19