Screening techniques for monitoring the sub-visible particle formation of free fatty acids in biopharmaceuticals.

Autor: Chen W; F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel, Switzerland., Klemm D; F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel, Switzerland., Gregoritza K; F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel, Switzerland., Satya Krishna Kishore R; F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel, Switzerland., Olaf Stracke J; F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel, Switzerland., Wurth C; F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel, Switzerland., Pinto C; F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel, Switzerland. Electronic address: cosimo.pinto@roche.com., Sancho Oltra N; F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel, Switzerland. Electronic address: nuria.sancho_oltra@roche.com.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2023 Sep; Vol. 190, pp. 242-247. Date of Electronic Publication: 2023 Jul 29.
DOI: 10.1016/j.ejpb.2023.07.018
Abstrakt: Free fatty acid (FFA) particles that originate from the enzymatic hydrolysis of polysorbate (PS) via co-purified host cell proteins generally appear abruptly in drug products during real-time (long-term) storage. Efforts were taken to understand the kinetics of FFA particle formation, aiming for a mitigation strategy. However, it is rather challenging particularly in the sub-visible particle (SVP) range, due to either the insufficient sensitivity of the analytical techniques used or the interference of the formulation matrices of proteinaceous drug products. In this study, we examined the feasibility of Raman microscopy, backgrounded membrane imaging (BMI) and total holographic characterization (THC) on the detection of FFA sub-visible particles (SVPs). The results indicate that THC is the most sensitive technique to track their occurrence during the course of PS hydrolysis. Moreover, with this technique we are able to distinguish different stages of FFA particle formation in the medium. In addition, a real time stability study of a biopharmaceutical was analyzed, demonstrating the viability of THC to monitor SVPs in a real sample and correlate it to the visible particles (VPs) occurrence.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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