Monitoring polysorbate hydrolysis in biopharmaceuticals using a QC-ready free fatty acid quantification method.

Autor: Honemann MN; F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland., Wendler J; F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland., Graf T; Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany., Bathke A; F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland., Bell CH; F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland. Electronic address: christian.bell@roche.com.
Jazyk: angličtina
Zdroj: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2019 May 15; Vol. 1116, pp. 1-8. Date of Electronic Publication: 2019 Mar 26.
DOI: 10.1016/j.jchromb.2019.03.030
Abstrakt: Hydrolysis of the non-ionic surfactant polysorbate upon long-term storage poses significant challenges to development of biopharmaceutical liquid formulations. Low concentrations of intact surfactant may compromise its protective properties and thus affect protein stability. In addition, accumulation of polysorbate hydrolysis products is increasingly put into context with the formation of visible and subvisible particulates based on the low solubility of the main degradation products. Despite of this potential negative impact on product quality, quantification of the released free fatty acids is performed commonly in an indirect and consequently insensitive manner by determining the remaining PS content or by cumbersome methods, which are unsuitable for routine testing in quality control laboratories. For this purpose, this study describes the development and qualification of a label-free, reliable liquid-chromatography single quad mass detector (LC-QDa)-based method capable of resolving slight changes in the free fatty acid profile which can be readily integrated into quality control facilities. The practical utility of the herein described method is outlined by a case study on the real-time storage stability of a formulated monoclonal antibody.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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