UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

A model based approach for identifying robust operating conditions for industrial chromatography with process variability

Close, EJ; Salm, JR; Bracewell, DG; Sorensen, E; (2014) A model based approach for identifying robust operating conditions for industrial chromatography with process variability. CHEMICAL ENGINEERING SCIENCE , 116 284 - 295. 10.1016/j.ces.2014.03.010. Green open access

[thumbnail of 1-s2.0-S0009250914001213-main.pdf] PDF
1-s2.0-S0009250914001213-main.pdf

Download (1MB)

Abstract

A model based approach has been developed and used to identify robust operating conditions for an industrial hydrophobic interaction chromatography where resin lot variability, combined with feed stream variability, was resulting in serious performance issues during the purification of a multi component therapeutic protein from crude feed material. An equilibrium dispersive model was formulated which successfully predicted the key product critical quality attribute during validation studies. The model was then used to identify operating parameter ranges that assured product quality despite the process variability. Probabilistic design spaces were generated using stochastic simulations that showed the probability that each resin lot would meet product quality specifications, over a range of possible operating conditions, accounting for the historical variability experienced in the load material composition and concentration. No operating condition was found with normal process variability where quality assurance remained >0.95 for resins that gave the highest and lowest product recoveries during process development. The lowest risk of batch failure found was 16%, and operating conditions were not robust. We then extended the stochastic methodology used to generate probabilistic design spaces, to identify the level of control required on the load material composition and concentration to bring process robustness to an acceptable level, which is not possible using DOE experimental methods due to the impractical amount of resources that would be required. Although reducing inlet variability resulted in an increase in the assurance of product quality, the results indicated that changing operating conditions according to which resin lot is in use is the favorable option.

Type: Article
Title: A model based approach for identifying robust operating conditions for industrial chromatography with process variability
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ces.2014.03.010
Publisher version: http://dx.doi.org/10.1016/j.ces.2014.03.010
Language: English
Additional information: © 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
Keywords: Process systems modeling, Stochastic simulation, Quality by Design, Chromatography, Hydrophobic interaction
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Chemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/1447693
Downloads since deposit
269Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item