Rapid optimization of processes for the integrated purification of biopharmaceuticals
Straight-through chromatography, wherein the eluate from one column passes directly onto another column without adjustment, is one strategy to integrate and intensify manufacturing processes for biologics. Development and optimization of such straight-through chromatographic processes is a challenge...
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021
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| Online Access: | https://hdl.handle.net/1721.1/135519 |
| _version_ | 1826189051934277632 |
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| author | Crowell, Laura E Rodriguez, Sergio A Love, Kerry R Cramer, Steven M Love, J Christopher |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Crowell, Laura E Rodriguez, Sergio A Love, Kerry R Cramer, Steven M Love, J Christopher |
| author_sort | Crowell, Laura E |
| collection | MIT |
| description | Straight-through chromatography, wherein the eluate from one column passes directly onto another column without adjustment, is one strategy to integrate and intensify manufacturing processes for biologics. Development and optimization of such straight-through chromatographic processes is a challenge, however. Conventional high-throughput screening methods optimize each chromatographic step independently, with limited consideration for the connectivity of steps. Here, we demonstrate a method for the development and optimization of fully integrated, multi-column processes for straight-through purification. Selection of resins was performed using an in silico tool for the prediction of processes for straight-through purification based on a one-time characterization of host-cell proteins combined with the chromatographic behavior of the product. A two-step optimization was then conducted to determine the buffer conditions that maximized yield while minimizing process- and product-related impurities. This optimization of buffer conditions included a series of range-finding experiments on each individual column, similar to conventional screening, followed by the development of a statistical model for the fully integrated, multi-column process using design of experiments. We used this methodology to develop and optimize integrated purification processes for a single-domain antibody and a cytokine, obtaining yields of 88% and 86%, respectively, with process- and product-related variants reduced to phase-appropriate levels for nonclinical material. |
| first_indexed | 2024-09-23T08:09:07Z |
| format | Article |
| id | mit-1721.1/135519 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:09:07Z |
| publishDate | 2021 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1355192023-09-27T20:36:47Z Rapid optimization of processes for the integrated purification of biopharmaceuticals Crowell, Laura E Rodriguez, Sergio A Love, Kerry R Cramer, Steven M Love, J Christopher Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Biological Engineering Straight-through chromatography, wherein the eluate from one column passes directly onto another column without adjustment, is one strategy to integrate and intensify manufacturing processes for biologics. Development and optimization of such straight-through chromatographic processes is a challenge, however. Conventional high-throughput screening methods optimize each chromatographic step independently, with limited consideration for the connectivity of steps. Here, we demonstrate a method for the development and optimization of fully integrated, multi-column processes for straight-through purification. Selection of resins was performed using an in silico tool for the prediction of processes for straight-through purification based on a one-time characterization of host-cell proteins combined with the chromatographic behavior of the product. A two-step optimization was then conducted to determine the buffer conditions that maximized yield while minimizing process- and product-related impurities. This optimization of buffer conditions included a series of range-finding experiments on each individual column, similar to conventional screening, followed by the development of a statistical model for the fully integrated, multi-column process using design of experiments. We used this methodology to develop and optimize integrated purification processes for a single-domain antibody and a cytokine, obtaining yields of 88% and 86%, respectively, with process- and product-related variants reduced to phase-appropriate levels for nonclinical material. 2021-10-27T20:23:49Z 2021-10-27T20:23:49Z 2021 2021-06-22T16:48:41Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135519 en 10.1002/bit.27767 Biotechnology and Bioengineering Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Wiley Wiley |
| spellingShingle | Crowell, Laura E Rodriguez, Sergio A Love, Kerry R Cramer, Steven M Love, J Christopher Rapid optimization of processes for the integrated purification of biopharmaceuticals |
| title | Rapid optimization of processes for the integrated purification of biopharmaceuticals |
| title_full | Rapid optimization of processes for the integrated purification of biopharmaceuticals |
| title_fullStr | Rapid optimization of processes for the integrated purification of biopharmaceuticals |
| title_full_unstemmed | Rapid optimization of processes for the integrated purification of biopharmaceuticals |
| title_short | Rapid optimization of processes for the integrated purification of biopharmaceuticals |
| title_sort | rapid optimization of processes for the integrated purification of biopharmaceuticals |
| url | https://hdl.handle.net/1721.1/135519 |
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