In a maturing pharmaceutical industry, cost of production has the attention of management and science. An essential step of downstream processing is chromatography as it offers high selectivity and productivity. Therefore, the economic design and optimisation of a new chromatography operation is critical. Pharmaceutical companies frequently have limited time and material to make a full assessment of suitable chromatographic resins for a given purification process consisting of three or more chromatographic steps. In recent years, scale-down systems based on microplate format have been used to investigate purification conditions for therapeutic proteins by miniaturizing large scale 1000-fold. Their integration with robotic liquid dispensing systems has enabled high throughput studies. Appropriate mathematical models of the chromatographic separation may be used to convert the information provided by high throughput studies into quantitative predictions of large scale performance.<br/>This study aims to develop chromatographic first principles models from data obtained using chromatographic pipette tips (PhyTips; PhyNexus Inc., USA) on a Tecan robotic platform. The mathematical model used in this study is the general rate model. It is a comprehensive chromatography model which takes into account intra- and inter-particle mass transport, adsorption/desorption kinetics on the site of the particles and salt-induced elution. The predictive power of the integrated microscale experimentation and general rate modeling is challenged against experimentally obtained lab scale chromatograms. Windows of Operation for the large scale are then generated indicating the contours for different yield and throughput targets as a function of the critical process parameters (e.g. protein load, linear velocity).

Predicting cation exchange Fab purification using micro-tip chromatography and general rate modelling

251st National Meeting (2016)

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