A framework for assessing the solutions in chromatographic process design and operation for large‐scale manufacture

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