A Direct Approach for Process Development Using Single Column Experiments Results in Predictable Streamlined Multi‐Column Chromatography Bioprocesses. Issue 4 (27th November 2018)

• Record Type: Journal Article
• Authors: Utturkar, Aditya; Gillette, Keith; Sun, Chia‐Yun; Pagkaliwangan, Mark; Quesenberry, Rachel; Schofield, Mark
• Is Part Of: Biotechnology journal. Volume 14:Issue 4(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-11-27
• Subjects: bioprocess development -- chromatography -- downstream Processing -- protein purification; Biotechnology -- Periodicals; 660.605
• DOI: 10.1002/biot.201800243
• Languages: English
• ISSNs: 1860-6768

Abstract

Abstract : An emphasis on continuous monoclonal antibody (mAb) bioprocessing in the pharmaceutical industry necessitates effective approaches for downstream process development (PD). With a PD strategy, the process parameters are optimized to directly develop streamlined three‐step continuous chromatography processes. A design of experiment (DoE) approach with single column (batch mode) is used to simulate a multi‐column (continuous mode) purification method and characterize each chromatography step: Protein A capture, anion exchange, and mixed mode cation exchange. A novel and targeted approach to quickly characterize a DoE design space was employed and empirical modeling was used to define the capacity for multi‐column chromatography to accurately transfer the batch process to continuous mode of purification. This PD approach effectively mimics the continuous mode of operation and provides the flexibility to develop multiple continuous processes with target mAb recovery and purity. By implementing this PD strategy and the process parameters defined in batch mode, two robust and predictable continuous bioprocesses were developed within 7 weeks of investigation, which resulted in a total product yield of recovery at or above 74%, host cell protein (HCP) content below 5 ppm, and aggregate content below 1%. Abstract : With a process development (PD) strategy, process parameters are optimized to develop streamlined three‐step continuous (multi‐column) chromatography processes. Using a design of experiment approach, single column experiments are used to simulate multi‐column purification methods and characterize each chromatography step: Protein A capture, anion exchange, and mixed mode cation exchange. This PD approach effectively mimics the continuous mode of operation and provides the flexibility to develop multiple continuous processes with target mAb recovery and purity.