Upstream cell culture process characterization and in-process control strategy development at pandemic speed
As of early 2022, the coronavirus disease 2019 (COVID-19) pandemic remains a substantial global health concern. Different treatments for COVID-19, such as anti-COVID-19 neutralizing monoclonal antibodies (mAbs), have been developed under tight timelines. Not only mAb product and clinical development...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | mAbs |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2022.2060724 |
| _version_ | 1818348809346875392 |
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| author | Jianlin Xu Jianfa Ou Kyle P. McHugh Michael C. Borys Anurag Khetan |
| author_facet | Jianlin Xu Jianfa Ou Kyle P. McHugh Michael C. Borys Anurag Khetan |
| author_sort | Jianlin Xu |
| collection | DOAJ |
| description | As of early 2022, the coronavirus disease 2019 (COVID-19) pandemic remains a substantial global health concern. Different treatments for COVID-19, such as anti-COVID-19 neutralizing monoclonal antibodies (mAbs), have been developed under tight timelines. Not only mAb product and clinical development but also chemistry, manufacturing, and controls (CMC) process development at pandemic speed are required to address this highly unmet patient need. CMC development consists of early- and late-stage process development to ensure sufficient mAb manufacturing yield and consistent product quality for patient safety and efficacy. Here, we report a case study of late-stage cell culture process development at pandemic speed for mAb1 and mAb2 production as a combination therapy for a highly unmet patient treatment. We completed late-stage cell culture process characterization (PC) within approximately 4 months from the cell culture process definition to the initiation of the manufacturing process performance qualification (PPQ) campaign for mAb1 and mAb2, in comparison to a standard one-year PC timeline. Different strategies were presented in detail at different PC steps, i.e., pre-PC risk assessment, scale-down model development and qualification, formal PC experiments, and in-process control strategy development for a successful PPQ campaign that did not sacrifice quality. The strategies we present may be applied to accelerate late-stage process development for other biologics to reduce timelines. |
| first_indexed | 2024-12-13T17:55:57Z |
| format | Article |
| id | doaj.art-f6b90d57fb154df5a121da03dc249e1e |
| institution | Directory Open Access Journal |
| issn | 1942-0862 1942-0870 |
| language | English |
| last_indexed | 2024-12-13T17:55:57Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj.art-f6b90d57fb154df5a121da03dc249e1e2022-12-21T23:36:22ZengTaylor & Francis GroupmAbs1942-08621942-08702022-12-0114110.1080/19420862.2022.2060724Upstream cell culture process characterization and in-process control strategy development at pandemic speedJianlin Xu0Jianfa Ou1Kyle P. McHugh2Michael C. Borys3Anurag Khetan4Biologics Development, Global Product Development and Supply, Bristol Myers Squibb, Devens, MA, USABiologics Development, Global Product Development and Supply, Bristol Myers Squibb, Devens, MA, USABiologics Development, Global Product Development and Supply, Bristol Myers Squibb, Devens, MA, USABiologics Development, Global Product Development and Supply, Bristol Myers Squibb, Devens, MA, USABiologics Development, Global Product Development and Supply, Bristol Myers Squibb, Devens, MA, USAAs of early 2022, the coronavirus disease 2019 (COVID-19) pandemic remains a substantial global health concern. Different treatments for COVID-19, such as anti-COVID-19 neutralizing monoclonal antibodies (mAbs), have been developed under tight timelines. Not only mAb product and clinical development but also chemistry, manufacturing, and controls (CMC) process development at pandemic speed are required to address this highly unmet patient need. CMC development consists of early- and late-stage process development to ensure sufficient mAb manufacturing yield and consistent product quality for patient safety and efficacy. Here, we report a case study of late-stage cell culture process development at pandemic speed for mAb1 and mAb2 production as a combination therapy for a highly unmet patient treatment. We completed late-stage cell culture process characterization (PC) within approximately 4 months from the cell culture process definition to the initiation of the manufacturing process performance qualification (PPQ) campaign for mAb1 and mAb2, in comparison to a standard one-year PC timeline. Different strategies were presented in detail at different PC steps, i.e., pre-PC risk assessment, scale-down model development and qualification, formal PC experiments, and in-process control strategy development for a successful PPQ campaign that did not sacrifice quality. The strategies we present may be applied to accelerate late-stage process development for other biologics to reduce timelines.https://www.tandfonline.com/doi/10.1080/19420862.2022.2060724Process characterization (PC)process performance qualification (PPQ)in-process control (IPC)Chinese hamster ovary (CHO) cell culture platformscale-down model (SDM)design of experiment (DOE) |
| spellingShingle | Jianlin Xu Jianfa Ou Kyle P. McHugh Michael C. Borys Anurag Khetan Upstream cell culture process characterization and in-process control strategy development at pandemic speed mAbs Process characterization (PC) process performance qualification (PPQ) in-process control (IPC) Chinese hamster ovary (CHO) cell culture platform scale-down model (SDM) design of experiment (DOE) |
| title | Upstream cell culture process characterization and in-process control strategy development at pandemic speed |
| title_full | Upstream cell culture process characterization and in-process control strategy development at pandemic speed |
| title_fullStr | Upstream cell culture process characterization and in-process control strategy development at pandemic speed |
| title_full_unstemmed | Upstream cell culture process characterization and in-process control strategy development at pandemic speed |
| title_short | Upstream cell culture process characterization and in-process control strategy development at pandemic speed |
| title_sort | upstream cell culture process characterization and in process control strategy development at pandemic speed |
| topic | Process characterization (PC) process performance qualification (PPQ) in-process control (IPC) Chinese hamster ovary (CHO) cell culture platform scale-down model (SDM) design of experiment (DOE) |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2022.2060724 |
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