Use of Quality by the Design for the Modelling of Chromatographic Separations

Abstract A desired goal of the PAT framework is to design and develop well understood processes that will consistently ensure a predefined quality at the end of the manufacturing process.[ 1 ] Achieving this goal will reduce the time and cost of process development and ensure development of robust processes that can handle variability and deliver a predefined quality as regards yield, purity and productivity within the defined design space. This communication will focus on a set of scientific principles supporting process understanding and process design of chromatographic separations.

[1]  J. Mollerup,et al.  The thermodynamic principles of ligand binding in chromatography and biology. , 2007, Journal of biotechnology.

[2]  Alois Jungbauer,et al.  Whey proteins as a model system for chromatographic separation of proteins. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[3]  Anurag S Rathore,et al.  Case study and application of process analytical technology (PAT) towards bioprocessing: Use of on‐line high‐performance liquid chromatography (HPLC) for making real‐time pooling decisions for process chromatography , 2008, Biotechnology and bioengineering.

[4]  David Chilin,et al.  Applying process analytical technology to biotech unit operations , 2006 .

[5]  Lawrence X. Yu.  Pharmaceutical Quality by Design: Product and Process Development, Understanding, and Control , 2008, Pharmaceutical Research.

[6]  Steven M. Cramer,et al.  Steric mass‐action ion exchange: Displacement profiles and induced salt gradients , 1992 .

[7]  Steven M Cramer,et al.  Prediction of protein retention times in gradient hydrophobic interaction chromatographic systems. , 2008, Journal of chromatography. A.

[8]  Jürgen Hubbuch,et al.  High Throughput Screening of Chromatographic Phases for Rapid Process Development , 2005 .

[9]  Anurag S. Rathore,et al.  Modeling of Biopharmaceutical Processes. part2: Process Chromatography Unit Opération , 2008 .

[10]  J A Asenjo,et al.  Application of chromatographic theory for process characterization towards validation of an ion‐exchange operation , 2007, Biotechnology and bioengineering.

[11]  Jørgen Mollerup,et al.  A review of the thermodynamics of protein association to ligands, protein adsorption, and adsorption isotherms , 2008 .

[12]  Jörg Thömmes,et al.  Modeling of protein monomer/aggregate purification and separation using hydrophobic interaction chromatography , 2008, Bioprocess and biosystems engineering.

[13]  Arne Staby,et al.  Quality by design--thermodynamic modelling of chromatographic separation of proteins. , 2008, Journal of chromatography. A.

[14]  Anita M. Katti,et al.  Fundamentals of Preparative and Nonlinear Chromatography , 1994 .

[15]  Arne Staby,et al.  Development, modelling, optimisation and scale-up of chromatographic purification of a therapeutic protein , 2007 .