Raman spectroscopy as an alternative rapid microbial bioburden test method for continuous, automated detection of contamination in biopharmaceutical drug substance manufacturing
To investigate an in-line Raman method capable of detecting accidental microbial contamination in pharmaceutical vessels, such as bioreactors producing monoclonal antibodies via cell culture. The Raman method consists of a multivariate model built from Raman spectra collected in-line during reduced-...
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Published in | Journal of applied microbiology Vol. 135; no. 8 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
England
05.08.2024
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Subjects | |
Online Access | Get full text |
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Summary: | To investigate an in-line Raman method capable of detecting accidental microbial contamination in pharmaceutical vessels, such as bioreactors producing monoclonal antibodies via cell culture.
The Raman method consists of a multivariate model built from Raman spectra collected in-line during reduced-scale bioreactor batches producing a monoclonal antibody, as well as a reduced-scale process with intentional spiking of representative compendial method microorganisms (n = 4). The orthogonal partial least squares regression discriminant analysis model (OPLS-DA) Area Under the Curve (AUC), specificity and sensitivity were 0.96, 0.99 and 0.95, respectively. Furthermore, the model successfully detected contamination in an accidentally contaminated manufacturing-scale batch. In all cases, the time to detection (TTD) for Raman was superior compared to offline, traditional microbiological culturing.
The Raman OPLS-DA method met acceptance criteria for equivalent decision making to be considered a viable alternative to the compendial method for in-process bioburden testing. The in-line method is automated, non-destructive, and provides a continuous assessment of bioburden compared to an offline compendial method, which is manual, results in loss of product, and in practice is only collected once daily and requires 3-5 days for enumeration. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1365-2672 1365-2672 |
DOI: | 10.1093/jambio/lxae188 |