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Tytuł pozycji:

Introduction and clearance of beta-glucan in the downstream processing of monoclonal antibodies.

Tytuł :
Introduction and clearance of beta-glucan in the downstream processing of monoclonal antibodies.
Autorzy :
Kluters S; Late Stage DSP Development, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Baden-Württemberg, Germany.
Steinhauser K; Late Stage DSP Development, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Baden-Württemberg, Germany.
Pfänder R; Late Stage DSP Development, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Baden-Württemberg, Germany.
Studts J; Late Stage DSP Development, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Baden-Württemberg, Germany.
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Źródło :
Biotechnology progress [Biotechnol Prog] 2021 Mar 20, pp. e3149. Date of Electronic Publication: 2021 Mar 20.
Publication Model :
Ahead of Print
Typ publikacji :
Journal Article
Język :
Imprint Name(s) :
Publication: <2010-> : Hoboken, NJ : Wiley-Blackwell
Original Publication: [New York, N.Y. : American Institute of Chemical Engineers, c1985-
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Grant Information :
Boehringer Ingelheim
Contributed Indexing :
Keywords: depth filtration; downstream processing; monoclonal antibody; process-related impurities; β-glucan
Entry Date(s) :
Date Created: 20210320 Latest Revision: 20210331
Update Code :
Czasopismo naukowe
β-Glucan process-related impurities can be introduced into biopharmaceutical products via upstream or downstream processing or via excipients. This study obtained a comprehensive process-mapping dataset for five monoclonal antibodies to assess β-glucan introduction and clearance during development and production runs at various scales. Overall, 198 data points were available for analysis. The greatest β-glucan concentrations were found in the depth-filtration filtrate (37-2,745 pg/ml). Load volume correlated with β-glucan concentration in the filtrate, whereas flush volume was of secondary importance. Cation-exchange chromatography significantly cleared β-glucans. Furthermore, β-glucan leaching from the Planova 20N virus removal filter was reduced by increasing the flush volume (1 vs. 10 L/m 2 ). β-glucan concentrations after filter flush with 10 L/m 2 were consistently <10 pg/ml. No or only limited β-glucan clearance was attained via ultrafiltration/diafiltration (UF/DF). However, during the first run with monoclonal antibody (mAb) 4, β-glucan concentration in the UF/DF retentate was 10.8 pg/mg, potentially due to β-glucan leaching from the first run with a regenerated cellulose membrane. Overall, β-glucan levels in the final mAb drug substance were 1-12 pg/mg. Assuming high doses of 1,000-5,000 mg, a β-glucan contamination at 20 pg/mg would translate to 20-100 ng/dose, which is below the previously suggested threshold for product safety (≤500 ng/dose).
(© 2021 The Authors. Biotechnology Progress published by Wiley Periodicals LLC. on behalf of American Institute of Chemical Engineers.)

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