Protein A chromatography increases monoclonal antibody aggregation rate during subsequent low pH virus inactivation hold

Journal of Chromatography. a
Alice R MazzerDaniel G Bracewell

Abstract

Protein A chromatography is a near-ubiquitous method of mAb capture in bioprocesses. The use of low pH buffer for elution from protein A is known to contribute to product aggregation. Yet, a more limited set of evidence suggests that low pH may not be the sole cause of aggregation in protein A chromatography, rather, other facets of the process may contribute significantly. This paper presents a well-defined method for investigating this problem. An IgG4 was incubated in elution buffer after protein A chromatography (typical of the viral inactivation hold) and the quantity of monomer in neutralised samples was determined by size exclusion chromatography; elution buffers of different pH values predetermined to induce aggregation of the IgG4 were used. Rate constants for monomer decay over time were determined by fitting exponential decay functions to the data. Similar experiments were implemented in the absence of a chromatography step, i.e. IgG4 aggregation at low pH. Rate constants for aggregation after protein A chromatography were considerably higher than those from low pH exposure alone; a distinct shift in aggregation rates was apparent across the pH range tested.

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Citations

Feb 3, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Egbert Müller, Judith Vajda
Jan 26, 2016·Journal of Chromatography. a·Pete Gagnon, Rui Nian
May 10, 2016·International Journal of Biological Macromolecules·Kinjal A PatelIpsita Roy
Dec 3, 2016·Pharmaceutical Development and Technology·Mouhamad Reslan, Veysel Kayser
Jan 10, 2018·Biotechnology and Bioengineering·Monika FarysRichard Kucia-Tran
Mar 9, 2018·Critical Reviews in Biotechnology·Micael KarlbergJarka Glassey
Aug 7, 2018·Biotechnology and Bioengineering·Balaji SomasundaramLinda H L Lua
Apr 5, 2019·Biotechnology Journal·Gonçalo F L da SilvaAna C M Dias-Cabral
Dec 1, 2019·Biotechnology and Bioengineering·Ruben WälchliMassimo Morbidelli
Mar 18, 2020·PloS One·Hiroshi NamisakiNobuaki Takahashi
Jun 25, 2020·Biotechnology Journal·Raquel Dos SantosAna Cecília A Roque
Jul 14, 2020·Frontiers in Bioengineering and Biotechnology·Steffen C HinzHarald Kolmar
Apr 13, 2017·Frontiers in Microbiology·Abdullah F U H SaeedShihua Wang
Jan 8, 2021·Journal of Chromatography. a·Julia Scheffel, Sophia Hober
Apr 24, 2020·Computational and Structural Biotechnology Journal·Max HebditchJim Warwicker
Jun 13, 2020·International Journal of Pharmaceutics·Ngoc B Pham, Wilson S Meng
Apr 16, 2017·Journal of Chromatography. a·Alice R MazzerDaniel G Bracewell
Dec 28, 2019·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Hannah ReeseStefano Menegatti
Jul 19, 2021·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Carolin StangeChristian Frech
Sep 14, 2018·Analytical Chemistry·Li ZhouWilliam Blaine Stine

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Methods Mentioned

BETA
differential scanning calorimetry
Size

Software Mentioned

AKTA
Unicorn
OriginLab
ChemStation
OriginPro

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