Risk control of host cell proteins in one therapeutic antibody produced by concentrated fed‐batch (CFB) mode
Abstract Multiple control strategies, including a downstream purification process with well‐controlled parameters and a comprehensive release or characterization for intermediates or drug substances, were implemented to mitigate the potential risk of host cell proteins (HCPs) in one concentrated fed...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley-VCH
2023-03-01
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| Series: | Engineering in Life Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/elsc.202200060 |
| _version_ | 1811161478562054144 |
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| author | Yiling Lu Jun Lin Tianze Bian Jin Chen Dan Liu Mingjun Ma Zhen Gao Jiemin Chen Dianwen Ju Xing Wang |
| author_facet | Yiling Lu Jun Lin Tianze Bian Jin Chen Dan Liu Mingjun Ma Zhen Gao Jiemin Chen Dianwen Ju Xing Wang |
| author_sort | Yiling Lu |
| collection | DOAJ |
| description | Abstract Multiple control strategies, including a downstream purification process with well‐controlled parameters and a comprehensive release or characterization for intermediates or drug substances, were implemented to mitigate the potential risk of host cell proteins (HCPs) in one concentrated fed‐batch (CFB) mode manufactured product. A host cell process specific enzyme‐linked immunosorbent assay (ELISA) method was developed for the quantitation of HCPs. The method was fully validated and showed good performance including high antibody coverage. This was confirmed by 2D Gel‐Western Blot analysis. Furthermore, a LC‐MS/MS method with non‐denaturing digestion and a long gradient chromatographic separation coupled with data dependent acquisition (DDA) on a Thermo/QE‐HF‐X mass spectrometer was developed as an orthogonal method to help identify the specific types of HCPs in this CFB product. Because of the high sensitivity, selectivity and adaptability of the new developed LC‐MS/MS method, significantly more species of HCP contaminants were able to be identified. Even though high levels of HCPs were observed in the harvest bulk of this CFB product, the development of multiple processes and analytical control strategies may greatly mitigate potential risks and reduce HCPs contaminants to a very low level. No high‐risk HCP was identified and the total amount of HCPs was very low in the CFB final product. |
| first_indexed | 2024-04-10T06:14:51Z |
| format | Article |
| id | doaj.art-35b8e0e483434c36ad9dc92c362ffee4 |
| institution | Directory Open Access Journal |
| issn | 1618-0240 1618-2863 |
| language | English |
| last_indexed | 2024-04-10T06:14:51Z |
| publishDate | 2023-03-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Engineering in Life Sciences |
| spelling | doaj.art-35b8e0e483434c36ad9dc92c362ffee42023-03-02T08:33:12ZengWiley-VCHEngineering in Life Sciences1618-02401618-28632023-03-01233n/an/a10.1002/elsc.202200060Risk control of host cell proteins in one therapeutic antibody produced by concentrated fed‐batch (CFB) modeYiling Lu0Jun Lin1Tianze Bian2Jin Chen3Dan Liu4Mingjun Ma5Zhen Gao6Jiemin Chen7Dianwen Ju8Xing Wang9Department of Analytical Science Formulation & Quality Control, Genor Biopharma Co., Ltd. Shanghai ChinaDepartment of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy Shanghai ChinaDepartment of Analytical Science Formulation & Quality Control, Genor Biopharma Co., Ltd. Shanghai ChinaDepartment of Analytical Science Formulation & Quality Control, Genor Biopharma Co., Ltd. Shanghai ChinaDepartment of Analytical Science Formulation & Quality Control, Genor Biopharma Co., Ltd. Shanghai ChinaDepartment of Analytical Science Formulation & Quality Control, Genor Biopharma Co., Ltd. Shanghai ChinaDepartment of Analytical Science Formulation & Quality Control, Genor Biopharma Co., Ltd. Shanghai ChinaDepartment of Analytical Science Formulation & Quality Control, Genor Biopharma Co., Ltd. Shanghai ChinaDepartment of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy Shanghai ChinaArray Bridge Inc. St. Louis Missouri USAAbstract Multiple control strategies, including a downstream purification process with well‐controlled parameters and a comprehensive release or characterization for intermediates or drug substances, were implemented to mitigate the potential risk of host cell proteins (HCPs) in one concentrated fed‐batch (CFB) mode manufactured product. A host cell process specific enzyme‐linked immunosorbent assay (ELISA) method was developed for the quantitation of HCPs. The method was fully validated and showed good performance including high antibody coverage. This was confirmed by 2D Gel‐Western Blot analysis. Furthermore, a LC‐MS/MS method with non‐denaturing digestion and a long gradient chromatographic separation coupled with data dependent acquisition (DDA) on a Thermo/QE‐HF‐X mass spectrometer was developed as an orthogonal method to help identify the specific types of HCPs in this CFB product. Because of the high sensitivity, selectivity and adaptability of the new developed LC‐MS/MS method, significantly more species of HCP contaminants were able to be identified. Even though high levels of HCPs were observed in the harvest bulk of this CFB product, the development of multiple processes and analytical control strategies may greatly mitigate potential risks and reduce HCPs contaminants to a very low level. No high‐risk HCP was identified and the total amount of HCPs was very low in the CFB final product.https://doi.org/10.1002/elsc.202200060concentrated fed‐batch (CFB)ELISAhost cell proteins (HCPs)mass spectrum (MS)risk control |
| spellingShingle | Yiling Lu Jun Lin Tianze Bian Jin Chen Dan Liu Mingjun Ma Zhen Gao Jiemin Chen Dianwen Ju Xing Wang Risk control of host cell proteins in one therapeutic antibody produced by concentrated fed‐batch (CFB) mode Engineering in Life Sciences concentrated fed‐batch (CFB) ELISA host cell proteins (HCPs) mass spectrum (MS) risk control |
| title | Risk control of host cell proteins in one therapeutic antibody produced by concentrated fed‐batch (CFB) mode |
| title_full | Risk control of host cell proteins in one therapeutic antibody produced by concentrated fed‐batch (CFB) mode |
| title_fullStr | Risk control of host cell proteins in one therapeutic antibody produced by concentrated fed‐batch (CFB) mode |
| title_full_unstemmed | Risk control of host cell proteins in one therapeutic antibody produced by concentrated fed‐batch (CFB) mode |
| title_short | Risk control of host cell proteins in one therapeutic antibody produced by concentrated fed‐batch (CFB) mode |
| title_sort | risk control of host cell proteins in one therapeutic antibody produced by concentrated fed batch cfb mode |
| topic | concentrated fed‐batch (CFB) ELISA host cell proteins (HCPs) mass spectrum (MS) risk control |
| url | https://doi.org/10.1002/elsc.202200060 |
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