Quantitative characterization of leachables sinks in biopharmaceutical downstream processing.

Autor: Paudel K; Sartorius Stedim Biotech GmbH, August-Spindler-Straße 11, 37079 Goettingen, Germany. Electronic address: kushalpaudel@outlook.de., Hauk A; Sartorius Stedim Biotech GmbH, August-Spindler-Straße 11, 37079 Goettingen, Germany., Maier TV; Sartorius Stedim Biotech GmbH, August-Spindler-Straße 11, 37079 Goettingen, Germany., Menzel R; Sartorius Stedim Biotech GmbH, August-Spindler-Straße 11, 37079 Goettingen, Germany.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2020 Feb 15; Vol. 143, pp. 105069. Date of Electronic Publication: 2019 Oct 18.
DOI: 10.1016/j.ejps.2019.105069
Abstrakt: This article demonstrates, on a quantitative level, that leachables - potentially accumulated during a biopharmaceutical manufacturing process - will be significantly reduced/removed during four key downstream process steps: cell removal using centrifugation or depth filtration, sterile filtration and virus filtration. Eight common leachables model compounds (LMCs) were spiked into typical feed solutions containing buffer and proteins and were analyzed post-processing in the supernatant or filtrates by HPLC-UV. The clearance rates were calculated as the quotient between the scavenged and initially spiked amount of each leachable. High clearance rates were found for hydrophobic LMCs for all investigated downstream operation steps. It is shown that the removal of cells and cell debris from a culture broth reduces the amount of LMCs almost completely after centrifugation or depth filtration. Also, sterilizing-grade and virus filtration provided a high scavenger effect to most of the LMCs. In contrast, only one hydrophilic acid was not significantly scavenged by the described operations. The possibility to include leachables sinks to a process qualification and risk mitigation concept is explained.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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