Flow Water Proton NMR: In-Line Process Analytical Technology for Continuous Biomanufacturing.

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TitleFlow Water Proton NMR: In-Line Process Analytical Technology for Continuous Biomanufacturing.
Publication TypeJournal Article
Year of Publication2019
AuthorsTaraban, MB, Briggs, KT, Merkel, P, Y Yu, B
JournalAnal Chem
Date Published2019 Oct 08
ISSN1520-6882
Abstract

Continuous manufacturing of biologics is one of the priorities of the biopharmaceutical industry. However, its widespread implementation is hampered by a lack of noninvasive/nondestructive process analytical technology (PAT) systems capable of real-time in-line monitoring of product flow parameters, such as concentration and/or aggregate content. We have previously demonstrated that, under nonflow conditions, the water proton transverse relaxation rate, (HO), is sensitive to protein concentration and aggregate content in biopharmaceutical formulations. In the present work, we explored the potential of water proton NMR under flow conditions (flow-NMR) to use (HO) as a quantitative indicator of protein concentration variations and aggregate levels in the process flow. We show that, under flow conditions, (HO) is sensitive to rather small changes in protein concentration (<1 mg/mL) and is capable to detect variations in the aggregate content of <1%. Our findings suggest that flow-NMR could be advantageously used as a real-time in-line noninvasive PAT for continuous biomanufacturing.

DOI10.1021/acs.analchem.9b02622
Alternate JournalAnal. Chem.
PubMed ID31550145