Quantifying Process Tradeoffs in the Operation of Chromatographic Sequences

摘要

A method for the rapid representation of key process tradeoffs that need to be made during the analysis of chromatographic sequences has been proposed. It involves the construction of fractionation and maximum purification factor versus yield diagrams, which can be completed easily on the basis of chromatographic data. The output of the framework developed reflects the degree of tradeoff between levels of yield and purity and provides a fast and precise prediction of the sample fraction collection strategy needed to meet a desired process specification. The usefulness of this approach for the purpose of product purification adn contaminent removal in a single chromatographic step has been successfully demonstrated in an earlier paper and it is now extended by application to a chromatographic sequence: the separation of a hypothetical three-component protein system by hydrophobic interaction chromatography (HIC) followed by size exclusion chromatography (SEC). The HIC operation has a strong impact upon the subsequent SEC step. The studies show how the analysis of performance in such a chromatographic sequence can be carried out easily and in a straightforward fashion using the fractionation diagram approach. The methodology proposed serves as a useful tool for identifying the process tradeoffs that must be made durig operation of a sequence of chromatographic steps and indicates the impact on further processing of the cut-point decisions that are made.