Detergent-Mediated Virus Inactivation in Biotechnological Matrices: More than Just CMC
For decades, the ability of detergents to solubilize biological membranes has been utilized in biotechnological manufacturing to disrupt the lipid envelope of potentially contaminating viruses and thus enhance the safety margins of plasma- and cell-derived drugs. This ability has been linked to dete...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/7920 |
| _version_ | 1797602433070792704 |
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| author | Jean-Baptiste Farcet Michael Karbiener Leonhard Zelger Johanna Kindermann Thomas R. Kreil |
| author_facet | Jean-Baptiste Farcet Michael Karbiener Leonhard Zelger Johanna Kindermann Thomas R. Kreil |
| author_sort | Jean-Baptiste Farcet |
| collection | DOAJ |
| description | For decades, the ability of detergents to solubilize biological membranes has been utilized in biotechnological manufacturing to disrupt the lipid envelope of potentially contaminating viruses and thus enhance the safety margins of plasma- and cell-derived drugs. This ability has been linked to detergent micelles, which are formed if the concentration of detergent molecules exceeds the critical micelle concentration (CMC). Traditionally, the CMC of detergents is determined in deionized water (ddH<sub>2</sub>O), i.e., a situation considerably different from the actual situation of biotechnological manufacturing. This study compared, for five distinct detergents, the CMC in ddH<sub>2</sub>O side-by-side with two biopharmaceutical process intermediates relevant to plasma-derived (Immunoglobulin) and cell-derived (monoclonal antibody) products, respectively. Depending on the matrix, the CMC of detergents changed by a factor of up to ~4-fold. Further, the CMC in biotechnological matrices did not correlate with antiviral potency, as Triton X-100 (TX-100) and similar detergents had comparatively higher CMCs than polysorbate-based detergents, which are known to be less potent in terms of virus inactivation. Finally, it was demonstrated that TX-100 and similar detergents also have virus-inactivating properties if applied below the CMC. Thus, the presence of detergent micelles might not be an absolute prerequisite for the disruption of virus envelopes. |
| first_indexed | 2024-03-11T04:16:58Z |
| format | Article |
| id | doaj.art-373af96d313c4e99a1d4f11a350924fa |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:16:58Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-373af96d313c4e99a1d4f11a350924fa2023-11-17T23:02:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01249792010.3390/ijms24097920Detergent-Mediated Virus Inactivation in Biotechnological Matrices: More than Just CMCJean-Baptiste Farcet0Michael Karbiener1Leonhard Zelger2Johanna Kindermann3Thomas R. Kreil4Pharmaceutical Sciences, Baxalta Innovations GmbH, Now Part of the Takeda Group of Companies, 1221 Vienna, AustriaGlobal Pathogen Safety, Takeda Manufacturing Austria AG, 1221 Vienna, AustriaGlobal Pathogen Safety, Takeda Manufacturing Austria AG, 1221 Vienna, AustriaGlobal Pathogen Safety, Takeda Manufacturing Austria AG, 1221 Vienna, AustriaGlobal Pathogen Safety, Takeda Manufacturing Austria AG, 1221 Vienna, AustriaFor decades, the ability of detergents to solubilize biological membranes has been utilized in biotechnological manufacturing to disrupt the lipid envelope of potentially contaminating viruses and thus enhance the safety margins of plasma- and cell-derived drugs. This ability has been linked to detergent micelles, which are formed if the concentration of detergent molecules exceeds the critical micelle concentration (CMC). Traditionally, the CMC of detergents is determined in deionized water (ddH<sub>2</sub>O), i.e., a situation considerably different from the actual situation of biotechnological manufacturing. This study compared, for five distinct detergents, the CMC in ddH<sub>2</sub>O side-by-side with two biopharmaceutical process intermediates relevant to plasma-derived (Immunoglobulin) and cell-derived (monoclonal antibody) products, respectively. Depending on the matrix, the CMC of detergents changed by a factor of up to ~4-fold. Further, the CMC in biotechnological matrices did not correlate with antiviral potency, as Triton X-100 (TX-100) and similar detergents had comparatively higher CMCs than polysorbate-based detergents, which are known to be less potent in terms of virus inactivation. Finally, it was demonstrated that TX-100 and similar detergents also have virus-inactivating properties if applied below the CMC. Thus, the presence of detergent micelles might not be an absolute prerequisite for the disruption of virus envelopes.https://www.mdpi.com/1422-0067/24/9/7920virus inactivationTriton X-100detergentNereidTriton X-100 reducedCMC |
| spellingShingle | Jean-Baptiste Farcet Michael Karbiener Leonhard Zelger Johanna Kindermann Thomas R. Kreil Detergent-Mediated Virus Inactivation in Biotechnological Matrices: More than Just CMC International Journal of Molecular Sciences virus inactivation Triton X-100 detergent Nereid Triton X-100 reduced CMC |
| title | Detergent-Mediated Virus Inactivation in Biotechnological Matrices: More than Just CMC |
| title_full | Detergent-Mediated Virus Inactivation in Biotechnological Matrices: More than Just CMC |
| title_fullStr | Detergent-Mediated Virus Inactivation in Biotechnological Matrices: More than Just CMC |
| title_full_unstemmed | Detergent-Mediated Virus Inactivation in Biotechnological Matrices: More than Just CMC |
| title_short | Detergent-Mediated Virus Inactivation in Biotechnological Matrices: More than Just CMC |
| title_sort | detergent mediated virus inactivation in biotechnological matrices more than just cmc |
| topic | virus inactivation Triton X-100 detergent Nereid Triton X-100 reduced CMC |
| url | https://www.mdpi.com/1422-0067/24/9/7920 |
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