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Article

Continuous Affinity Purification of Adeno-Associated Virus Using Periodic Counter-Current Chromatography

1
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal
2
ITQB NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal
3
Cytiva, 751 84 Uppsala, Sweden
*
Author to whom correspondence should be addressed.
Academic Editors: Ossi Korhonen and Tuomas Ervasti
Pharmaceutics 2022, 14(7), 1346; https://doi.org/10.3390/pharmaceutics14071346
Received: 19 May 2022 / Revised: 11 June 2022 / Accepted: 23 June 2022 / Published: 25 June 2022
(This article belongs to the Special Issue Continuous Pharmaceutical Manufacturing, Volume II)
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. View Full-Text
Keywords: adeno-associated virus; affinity purification; continuous processing; gene therapy; periodic counter-current chromatography adeno-associated virus; affinity purification; continuous processing; gene therapy; periodic counter-current chromatography
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MDPI and ACS Style

Mendes, J.P.; Bergman, M.; Solbrand, A.; Peixoto, C.; Carrondo, M.J.T.; Silva, R.J.S. Continuous Affinity Purification of Adeno-Associated Virus Using Periodic Counter-Current Chromatography. Pharmaceutics 2022, 14, 1346. https://doi.org/10.3390/pharmaceutics14071346

AMA Style

Mendes JP, Bergman M, Solbrand A, Peixoto C, Carrondo MJT, Silva RJS. Continuous Affinity Purification of Adeno-Associated Virus Using Periodic Counter-Current Chromatography. Pharmaceutics. 2022; 14(7):1346. https://doi.org/10.3390/pharmaceutics14071346

Chicago/Turabian Style

Mendes, João P., Magnus Bergman, Anita Solbrand, Cristina Peixoto, Manuel J. T. Carrondo, and Ricardo J. S. Silva. 2022. "Continuous Affinity Purification of Adeno-Associated Virus Using Periodic Counter-Current Chromatography" Pharmaceutics 14, no. 7: 1346. https://doi.org/10.3390/pharmaceutics14071346

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