• chromatography;
  • windows of operation;
  • feasible space;
  • decision-based modelling


Chromatographic separation of biopharmaceuticals is complex and tools for the prediction of performance and the trade-offs necessary for efficient operation are limited and time-consuming. This complexity is due to the large number of possible column aspect ratios that satisfy process and economic needs. This paper demonstrates a framework for the design and analysis of chromatographic steps. The functionalities are illustrated by application to a Protein A separation where the effects of column diameter, bed length and linear flow rate on cost of goods (COG/g) and productivity (g h−1) are investigated so as to identify the optimal operating strategy. Results are presented as a series of ‘windows of operation’ to address key design and operating decisions. The tool allows the designer to customise limiting constraints based on product- and process-specific knowledge. Results indicate the significant impact on COG/g of column oversizing and how this can be balanced by increased levels of productivity. Copyright © 2006 Society of Chemical Industry