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Process analytical technology for on‐line monitoring of quality attributes during single‐use ultrafiltration/diafiltration
Author(s) -
West Jay M.,
Feroz Hasin,
Xu Xia,
Puri Neha,
Holstein Melissa,
Ghose Sanchayita,
Ding Julia,
Li Z. J.
Publication year - 2021
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.27741
Subject(s) - diafiltration , process analytical technology , ultrafiltration (renal) , bioprocess , chromatography , cross flow filtration , downstream processing , filtration (mathematics) , critical quality attributes , process engineering , biopharmaceutical , chemistry , computer science , membrane , microbiology and biotechnology , engineering , mathematics , microfiltration , particle size , biochemistry , statistics , chemical engineering , biology
Process analytical technology (PAT) is a fast‐growing field within bioprocessing that enables innovation in biological drug manufacturing. This study demonstrates novel PAT methods for monitoring multiple quality attributes simultaneously during the ultrafiltration and diafiltration (UF/DF) process operation, the final step of monoclonal antibody (mAb) purification. Size exclusion chromatography (SEC) methods were developed to measure excipients arginine, histidine, and high molecular weight (HMW) species using a liquid chromatography (LC) system with autosampler for both on‐line and at‐line PAT modes. The methods were applied in UF/DF studies for the comparison of single‐use tangential flow filtration (TFF) cassettes to standard reusable cassettes to achieve very high concentration mAb drug substance (DS) in the order of 100–200 g/L. These case studies demonstrated that single‐use TFF cassettes are a functionally equivalent, low‐cost alternative to standard reusable cassettes, and that the on‐line PAT measurement of purity and excipient concentration was comparable to orthogonal offline methods. These PAT applications using an on‐line LC system equipped with onboard sample dilution can become a platform system for monitoring of multiple attributes over a wide dynamic range, a potentially valuable tool for biological drug development and manufacturing.