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Detection of low numbers of bacterial cells in pharmaceutical drug product using Raman Spectroscopy and PLS-DA multivariate analysis

View ORCID ProfileR.A. Grosso, View ORCID ProfileA.R. Walther, E. Brunbech, A. Sørensen, B. Schebye, K.E. Olsen, H. Qu, View ORCID ProfileM.A.B. Hedegaard, View ORCID ProfileE. C. Arnspang
doi: https://doi.org/10.1101/2022.04.26.489535
R.A. Grosso
1Department of Green Technology, SDU- Biotechnology, University of Southern Denmark, Odense, Denmark
2Product Supply Injectable Finished Products, Microbial Competence Centre, Novo Nordisk A/S, Copenhagen, Denmark
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  • ORCID record for R.A. Grosso
A.R. Walther
1Department of Green Technology, SDU- Biotechnology, University of Southern Denmark, Odense, Denmark
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E. Brunbech
2Product Supply Injectable Finished Products, Microbial Competence Centre, Novo Nordisk A/S, Copenhagen, Denmark
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A. Sørensen
2Product Supply Injectable Finished Products, Microbial Competence Centre, Novo Nordisk A/S, Copenhagen, Denmark
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B. Schebye
3Product Supply Injectable Finished Products, Technology Innovation, Novo Nordisk A/S, Copenhagen, Denmark
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K.E. Olsen
2Product Supply Injectable Finished Products, Microbial Competence Centre, Novo Nordisk A/S, Copenhagen, Denmark
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H. Qu
1Department of Green Technology, SDU- Biotechnology, University of Southern Denmark, Odense, Denmark
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M.A.B. Hedegaard
1Department of Green Technology, SDU- Biotechnology, University of Southern Denmark, Odense, Denmark
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E. C. Arnspang
1Department of Green Technology, SDU- Biotechnology, University of Southern Denmark, Odense, Denmark
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  • For correspondence: arnspang@igt.sdu.dk
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Abstract

Sterility testing is a laborious and slow process to detect contaminants present in drug products. Raman spectroscopy is a promising label-free tool to detect microorganisms and thus gaining relevance as future alternative culture-free method for sterility testing in pharmaceutical industry. However, reaching detection limits similar to standard procedures while keeping a high accuracy remains challenging, due to weak bacterial Raman signal. In this work, we show a new non-invasive approach focusing on detect different bacteria in concentrations below 100 CFU/ml within drug product containers using Raman spectroscopy and multivariate data analysis. Even though Raman spectra form drug product with and without bacteria are similar, a partial least squared discriminant analysis (PLS-DA) model shows great performance to distinguish samples with bacteria contaminants in limits below 10 CFU/ml. We use spiked samples with bacteria spores for independent validation achieving a detection accuracy of 99%. Our results indicate a great potential of this rapid, and cost-effective approach to be use in quality control of pharmaceutical industry.

Competing Interest Statement

The authors have declared no competing interest.

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Posted April 26, 2022.
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Detection of low numbers of bacterial cells in pharmaceutical drug product using Raman Spectroscopy and PLS-DA multivariate analysis
R.A. Grosso, A.R. Walther, E. Brunbech, A. Sørensen, B. Schebye, K.E. Olsen, H. Qu, M.A.B. Hedegaard, E. C. Arnspang
bioRxiv 2022.04.26.489535; doi: https://doi.org/10.1101/2022.04.26.489535
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Detection of low numbers of bacterial cells in pharmaceutical drug product using Raman Spectroscopy and PLS-DA multivariate analysis
R.A. Grosso, A.R. Walther, E. Brunbech, A. Sørensen, B. Schebye, K.E. Olsen, H. Qu, M.A.B. Hedegaard, E. C. Arnspang
bioRxiv 2022.04.26.489535; doi: https://doi.org/10.1101/2022.04.26.489535

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