Continuous Affinity Purification of Adeno-Associated Virus Using Periodic Counter-Current Chromatography
Replacing batch unit operations of biopharmaceuticals by continuous manufacturing is a maturing concept, with periodic counter-current chromatography (PCC) favoured to replace batch chromatography. Continuous affinity capture of adeno-associated virus (AAV) using PCC has the potential to cope with t...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/7/1346 |
| _version_ | 1797416462046986240 |
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| author | João P. Mendes Magnus Bergman Anita Solbrand Cristina Peixoto Manuel J. T. Carrondo Ricardo J. S. Silva |
| author_facet | João P. Mendes Magnus Bergman Anita Solbrand Cristina Peixoto Manuel J. T. Carrondo Ricardo J. S. Silva |
| author_sort | João P. Mendes |
| collection | DOAJ |
| description | Replacing batch unit operations of biopharmaceuticals by continuous manufacturing is a maturing concept, with periodic counter-current chromatography (PCC) favoured to replace batch chromatography. Continuous affinity capture of adeno-associated virus (AAV) using PCC has the potential to cope with the high doses required for AAV therapies thanks to its inherent high throughput. The implementation of continuous AAV affinity capture using a four-column PCC process is described herein. First, elution buffer screening was used to optimize virus recovery. Second, breakthrough curves were generated and described using a mechanistic model, which was later used to characterize the loading zone of the PCC. The experimental runs achieved a stable cyclic steady state yielding virus recoveries in line with the optimized batch process (>82%), with almost a three-fold improvement in productivity. The PCC affinity capture process developed here can bolster further improvements to process economics and manufacturing footprint, thereby contributing to the integrated continuous manufacturing concept. |
| first_indexed | 2024-03-09T06:04:37Z |
| format | Article |
| id | doaj.art-af19056809b94de4ba6fd2a19c130678 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T06:04:37Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-af19056809b94de4ba6fd2a19c1306782023-12-03T12:06:03ZengMDPI AGPharmaceutics1999-49232022-06-01147134610.3390/pharmaceutics14071346Continuous Affinity Purification of Adeno-Associated Virus Using Periodic Counter-Current ChromatographyJoão P. Mendes0Magnus Bergman1Anita Solbrand2Cristina Peixoto3Manuel J. T. Carrondo4Ricardo J. S. Silva5iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, PortugalCytiva, 751 84 Uppsala, SwedenCytiva, 751 84 Uppsala, SwedeniBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, PortugaliBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, PortugaliBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, PortugalReplacing batch unit operations of biopharmaceuticals by continuous manufacturing is a maturing concept, with periodic counter-current chromatography (PCC) favoured to replace batch chromatography. Continuous affinity capture of adeno-associated virus (AAV) using PCC has the potential to cope with the high doses required for AAV therapies thanks to its inherent high throughput. The implementation of continuous AAV affinity capture using a four-column PCC process is described herein. First, elution buffer screening was used to optimize virus recovery. Second, breakthrough curves were generated and described using a mechanistic model, which was later used to characterize the loading zone of the PCC. The experimental runs achieved a stable cyclic steady state yielding virus recoveries in line with the optimized batch process (>82%), with almost a three-fold improvement in productivity. The PCC affinity capture process developed here can bolster further improvements to process economics and manufacturing footprint, thereby contributing to the integrated continuous manufacturing concept.https://www.mdpi.com/1999-4923/14/7/1346adeno-associated virusaffinity purificationcontinuous processinggene therapyperiodic counter-current chromatography |
| spellingShingle | João P. Mendes Magnus Bergman Anita Solbrand Cristina Peixoto Manuel J. T. Carrondo Ricardo J. S. Silva Continuous Affinity Purification of Adeno-Associated Virus Using Periodic Counter-Current Chromatography Pharmaceutics adeno-associated virus affinity purification continuous processing gene therapy periodic counter-current chromatography |
| title | Continuous Affinity Purification of Adeno-Associated Virus Using Periodic Counter-Current Chromatography |
| title_full | Continuous Affinity Purification of Adeno-Associated Virus Using Periodic Counter-Current Chromatography |
| title_fullStr | Continuous Affinity Purification of Adeno-Associated Virus Using Periodic Counter-Current Chromatography |
| title_full_unstemmed | Continuous Affinity Purification of Adeno-Associated Virus Using Periodic Counter-Current Chromatography |
| title_short | Continuous Affinity Purification of Adeno-Associated Virus Using Periodic Counter-Current Chromatography |
| title_sort | continuous affinity purification of adeno associated virus using periodic counter current chromatography |
| topic | adeno-associated virus affinity purification continuous processing gene therapy periodic counter-current chromatography |
| url | https://www.mdpi.com/1999-4923/14/7/1346 |
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