Design of high productivity sequential multi-column chromatography for antibody capture

• The approach integrates process experimentation with modeling for SMCC design.
• The application of the approach to AbSolute for IgG capture was quick and easy.
• The generality of the approach based on the two case studies was exemplified.

An integrated experimental and modeling approach for the design of sequential multi-column chromatography (SMCC) is presented to maximize productivity in bioprocessing. The approach consists of three steps: (1) single-column model development and validation, (2) multi-column model development and validation, and (3) productivity optimization. The integrated use of process experimentation and modeling enables sufficient process understanding to be gained during process development such that the optimal SMCC design is found even with limited time and materials. The application of the approach is demonstrated by determining the optimal SMCC design that maximizes the capture of human IgG by a silica-based protein A adsorbent named AbSolute. For this example, the optimum productivity was found to increase from 2.9 kg L−1 day−1 for batch operation to 4.0 kg L−1 day−1 for SMCC operation with three columns. A second case study considering a hypothetical adsorbent of larger particle size and slower mass transfer is also presented, to further demonstrate the applicability of the integrated approach. The case studies clearly illustrate the capabilities of the integrated approach in quickly determining the optimal design and operation for an SMCC arrangement and with minimal, carefully targeted, experimentation.