Defining process design space for a hydrophobic interaction chromatography (HIC) purification step: Application of quality by design (QbD) principles

• Published in: Biotechnology and bioengineering Vol. 107; no. 6; pp. 985 - 997
• Main Authors: Jiang, Canping, Flansburg, Lisa, Ghose, Sanchayita, Jorjorian, Paul, Shukla, Abhinav A
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-12-2010; Wiley; Wiley Subscription Services, Inc
• Subjects: Biological and medical sciences; Biological Products - isolation & purification; Biotechnology; Biotechnology - methods; Cell culture; Chromatography; Chromatography - methods; Design; design space; Fc fusion protein; Fundamental and applied biological sciences. Psychology; Health. Pharmaceutical industry; Hydrophobic and Hydrophilic Interactions; hydrophobic interaction chromatography; Hydrophobic surfaces; Industrial applications and implications. Economical aspects; Molecular weight; Other active biomolecules; Pharmaceutical sciences; Production of active biomolecules; quality by design; Drug; Purification; Downstream processing; Hydrophobic interaction; Biopharmaceuticals; hydrophobic interaction chromatography; Design; Hydrophobic chromatography; Manufacturing process; Quality by design; Quality; Fc fusion protein; Fusion protein; design space
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.22894

The concept of design space has been taking root under the quality by design paradigm as a foundation of in‐process control strategies for biopharmaceutical manufacturing processes. This paper outlines the development of a design space for a hydrophobic interaction chromatography (HIC) process step. The design space included the impact of raw material lot‐to‐lot variability and variations in the feed stream from cell culture. A failure modes and effects analysis was employed as the basis for the process characterization exercise. During mapping of the process design space, the multi‐dimensional combination of operational variables were studied to quantify the impact on process performance in terms of yield and product quality. Variability in resin hydrophobicity was found to have a significant influence on step yield and high‐molecular weight aggregate clearance through the HIC step. A robust operating window was identified for this process step that enabled a higher step yield while ensuring acceptable product quality. Biotechnol. Bioeng. 2010;107: 985-997.