Purification of Protein by HIC: Mechanistic Modeling for Improved Understanding and Process Optimization

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BioPharm International, BioPharm International, April 2023, Volume 36, Issue 04
Pages: 22–29

In this article, a simple chromatographic model is proposed that is capable of predicting the impact of pH and ionic strength on HIC chromatograms.

Hydrophobic interaction chromatography (HIC) is a separation technique widely used for the purification of therapeutic proteins. The main leverages identified to operate HIC processes are solution pH and ionic strength. In this article, the authors show that simplistic mathematical models derived from statistical analysis cannot describe the impact of pH and ionic strength observed in HIC processes. A new mechanistic model accounting for the protein charge in solution (varying with pH) and the solution non-ideality (activity coefficient varying with the ionic strength) is proposed here. This simple model is shown to accurately describe experimental data and paves the way for numerical optimization of HIC processes.


Peer-reviewed research

Submitted Sept. 15, 2022
Accepted: Dec. 8, 2022.

About the authors

Lucrèce Nicoud*, lucrece.nicoud@ypso-facto.com, is head of product; Yohann Le Guennec is project manager; and Edouard Nicoud is head of customer success; all at Ypso-Facto, France. Antonio Cardillo, PhD, is expert scientist & GSK fellow; Elisa Innocenti is scientist; and Alessandro Pieri, PhD, is scientific leader & GSK associate fellow; all at GSK, Italy. Elena Lietta, PhD, is from Politecnico di Torino, Duca degli Abruzzi, Italy.

*To whom all correspondence should be addressed.

Article details

BioPharm International
Vol. 36, No. 4
April 2023
Pages: 22–29


When referring to this article, please cite it as Nicoud, L.; Le Guennec, Y.; Nicoud, E.; et al. Purification of Protein by HIC: Mechanistic Modeling for Improved Understanding and Process Optimization. BioPharm International 2023, 36 (4), 22–29.