title: Defining process design space for a hydrophobic interaction chromatography (HIC) purification step: application of quality by design (QbD) principles.
abstract: 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.
authors.affiliation: Manufacturing Sciences & Technology, Bristol-Myers Squibb Co., East Syracuse, New York 13057, USA.
authors.forename: Canping
authors.initials: C
authors.lastname: Jiang
authors.forename: Lisa
authors.initials: L
authors.lastname: Flansburg
authors.forename: Sanchayita
authors.initials: S
authors.lastname: Ghose
authors.forename: Paul
authors.initials: P
authors.lastname: Jorjorian
authors.forename: Abhinav A
authors.initials: AA
authors.lastname: Shukla
mesh_terms: D001688:Biological Products / Q000302:isolation & purification*; D001709:Biotechnology / Q000379:methods*; D002845:Chromatography / Q000379:methods*; D057927:Hydrophobic and Hydrophilic Interactions
chemical_list: D001688:Biological Products