Continuous crystallization as a downstream processing step of pharmaceutical proteins : a review
Continuous crystallization has been proposed as the downstream processing step for the purification of pharmaceutical proteins aimed at alleviating the manufacturing bottleneck caused by the limitations of chromatography-based operations at high upstream production titers. Herein we reviewed the cur...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2022
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| Online Access: | https://hdl.handle.net/10356/155138 |
| _version_ | 1826130011718942720 |
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| author | Pu, Siyu Hadinoto, Kunn |
| author2 | School of Chemical and Biomedical Engineering |
| author_facet | School of Chemical and Biomedical Engineering Pu, Siyu Hadinoto, Kunn |
| author_sort | Pu, Siyu |
| collection | NTU |
| description | Continuous crystallization has been proposed as the downstream processing step for the purification of pharmaceutical proteins aimed at alleviating the manufacturing bottleneck caused by the limitations of chromatography-based operations at high upstream production titers. Herein we reviewed the current state of research in continuous protein crystallization from which future research directions were identified. While the benefits of batch-to-continuous manufacturing transformation have been long established, progress in continuous protein crystallization lags behind its small-molecule counterpart. The reasons are because the challenging nature of protein crystallization, even when performed in the batch platform, and the lack of well-understood proteins available for thorough study. Nevertheless, successful batch-to-continuous transformations in both mixed-suspension-mixed-product-removal crystallizer and tubular crystallizers (i.e. slug flow, oscillatory baffled flow) have been demonstrated using lysozyme or monoclonal antibody as the model protein. Compared to the batch platform, the continuous platform produces comparable crystallization yield but with higher production capacity (g/h). Strategies to optimize the crystallizer's performance based on modeling and simulation results are also available. Future research should (1) study a wider range of proteins with impurities incorporated in the raw material streams, and (2) adopt advancements in continuous crystallization of small-molecule pharmaceuticals to improve the crystal quality and yield. |
| first_indexed | 2024-10-01T07:49:57Z |
| format | Journal Article |
| id | ntu-10356/155138 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:49:57Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1551382022-02-14T05:05:53Z Continuous crystallization as a downstream processing step of pharmaceutical proteins : a review Pu, Siyu Hadinoto, Kunn School of Chemical and Biomedical Engineering Engineering::Bioengineering Biopharmaceuticals Biologics Continuous crystallization has been proposed as the downstream processing step for the purification of pharmaceutical proteins aimed at alleviating the manufacturing bottleneck caused by the limitations of chromatography-based operations at high upstream production titers. Herein we reviewed the current state of research in continuous protein crystallization from which future research directions were identified. While the benefits of batch-to-continuous manufacturing transformation have been long established, progress in continuous protein crystallization lags behind its small-molecule counterpart. The reasons are because the challenging nature of protein crystallization, even when performed in the batch platform, and the lack of well-understood proteins available for thorough study. Nevertheless, successful batch-to-continuous transformations in both mixed-suspension-mixed-product-removal crystallizer and tubular crystallizers (i.e. slug flow, oscillatory baffled flow) have been demonstrated using lysozyme or monoclonal antibody as the model protein. Compared to the batch platform, the continuous platform produces comparable crystallization yield but with higher production capacity (g/h). Strategies to optimize the crystallizer's performance based on modeling and simulation results are also available. Future research should (1) study a wider range of proteins with impurities incorporated in the raw material streams, and (2) adopt advancements in continuous crystallization of small-molecule pharmaceuticals to improve the crystal quality and yield. Ministry of Education (MOE) The authors would like to thank the Ministry of Education Singapore for funding this work (Grant No. RG7/17 PI: Kunn Hadinoto Ong). 2022-02-14T05:05:53Z 2022-02-14T05:05:53Z 2020 Journal Article Pu, S. & Hadinoto, K. (2020). Continuous crystallization as a downstream processing step of pharmaceutical proteins : a review. Chemical Engineering Research and Design, 160, 89-104. https://dx.doi.org/10.1016/j.cherd.2020.05.004 0263-8762 https://hdl.handle.net/10356/155138 10.1016/j.cherd.2020.05.004 2-s2.0-85086463378 160 89 104 en RG7/17 Chemical Engineering Research and Design © 2020 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved. |
| spellingShingle | Engineering::Bioengineering Biopharmaceuticals Biologics Pu, Siyu Hadinoto, Kunn Continuous crystallization as a downstream processing step of pharmaceutical proteins : a review |
| title | Continuous crystallization as a downstream processing step of pharmaceutical proteins : a review |
| title_full | Continuous crystallization as a downstream processing step of pharmaceutical proteins : a review |
| title_fullStr | Continuous crystallization as a downstream processing step of pharmaceutical proteins : a review |
| title_full_unstemmed | Continuous crystallization as a downstream processing step of pharmaceutical proteins : a review |
| title_short | Continuous crystallization as a downstream processing step of pharmaceutical proteins : a review |
| title_sort | continuous crystallization as a downstream processing step of pharmaceutical proteins a review |
| topic | Engineering::Bioengineering Biopharmaceuticals Biologics |
| url | https://hdl.handle.net/10356/155138 |
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