Premium
Defining process design space for a hydrophobic interaction chromatography (HIC) purification step: Application of quality by design (QbD) principles
Author(s) -
Jiang Canping,
Flansburg Lisa,
Ghose Sanchayita,
Jorjorian Paul,
Shukla Abhinav A.
Publication year - 2010
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.22894
Subject(s) - quality by design , critical quality attributes , process engineering , process (computing) , process design , biopharmaceutical , yield (engineering) , hydrophilic interaction chromatography , computer science , biochemical engineering , quality (philosophy) , chromatography , biological system , chemistry , materials science , engineering , high performance liquid chromatography , microbiology and biotechnology , chemical engineering , process integration , philosophy , epistemology , particle size , metallurgy , biology , operating system
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. © 2010 Wiley Periodicals, Inc.