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As part of a viral mitigating strategy for continuous bioprocessing, that utilizes a plug flow reactor (PFR) for continuous viral inactivation (CVI), understanding the minimum residence time as a function of reactor scale and operational conditions is critical. An empirical-based model was utilized to calculate the minimum duration a virus particle experiences within a plug flow reactor as a function of reactor design and operational conditions. This empirical model's calculations were challenged by pulse injecting the bacteriophage ΦX-174 in non-inactivating conditions and monitoring the discharge of the PFR with infectivity assays. The initial proposed empirical model, with the constraint of requiring an operational Dean number of >100, proved to be effective at calculating first breakthrough of ΦX-174 but only for the appropriate Dean number conditions. With the knowledge gained from the first empirical model, a second was generated to eliminate the Dean number constraint. This second modified empirical model proved to be successful at calculating the first breakthrough at all Dean number's tested, however CVI operation at the lower Dean's number will lead to an increased asymmetry (i.e., increased tailing) in the residence time distribution.

Titel:	Utilizing bacteriophage to define the minimum residence time within a plug flow reactor.
Autor/in / Beteiligte Person:	Brown, MR ; Orozco, R
Link:	Full Text Finder (Volltext)
Zeitschrift:	Biotechnology and bioengineering, Jg. 118 (2021-09-01), Heft 9, S. 3367-3374
Veröffentlichung:	<2005->: Hoboken, NJ : Wiley ; <i>Original Publication</i>: New York, Wiley., 2021
Medientyp:	academicJournal
ISSN:	1097-0290 (electronic)
DOI:	10.1002/bit.27734
Schlagwort:	Bacteriophage phi X 174 Bioreactors Models, Biological Virus Inactivation
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Biotechnol Bioeng] 2021 Sep; Vol. 118 (9), pp. 3367-3374. <i>Date of Electronic Publication: </i>2021 Mar 11. MeSH Terms: Bacteriophage phi X 174* ; Bioreactors* ; Models, Biological* ; Virus Inactivation* References: Amarikwa, L. , Orozco, R. , Brown, M. , & Coffman, J. (2019). Impact of Dean vortices on the integrity testing of a continuous viral inactivation reactor. Biotechnol Journal, 2019(14), 1700726. https://doi.org/10.1002/biot.201700726. ; Arnold, L. , Lee, K. , Rucker-Pezzini, J. , & Lee, J. (2019). Implementation of fully integrated continuous antibody processing: Effects on productivity and COGm. Biotechnology Journal, 14, 1800061. https://doi.org/10.1002/biot.201800061. ; Brown, M. R. , Johnson, S. A. , Brorson, K. A. , Lute, S. C. , & Roush, D. J. (2017). A step-wise approach to define binding mechanisms of surrogate viral particles to multi-modal anion exchange resin in a single solute system. Biotechnology and Bioengineering, 114(7), 1487-1494. https://doi.org/10.1002/bit.26251. ; Brown, M. R. , Orozco, R. , & Coffman, J. (2020). Leveraging flow mechanics to determine critical process and scaling parameters in a continuous viral inactivation reactor. Biotechnology and Bioengineering, 117(3), 637-645. https://doi.org/10.1002/bit.27223, https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.27223. ; Gillespie, C. , Holstein, M. , Mullin, L. , Cotoni, K. , Caulmare, J. , & Greenhalgh, P. (2018). Continuous in-line virus inactivation for next generation bioprocessing. Biotechnology Journal, 2018, e1700718. https://doi.org/10.1002/biot.201700718. ; Johnson, S. , Brown, M. , Lute, S. , & Brorson, K. (2017). Adapting viral safety assurance strategies to continuous processing of biological products. Biotechnology and Bioengineering, 114(1), 21-32. https://doi.org/10.1002/bit.26060. ; Klutz, S. , Lobedann, M. , Bramsiepe, C. , & Schembecker, G. (2016). Continuous viral inactivation at low pH value in antibody manufacturing. Chemical Engineering and Processing: Process Intensification, 102, 88-101. https://doi.org/10.1016/j.cep.2016.01.002. ; Klutz, S. , Magnus, J. , Lobedann, M. , Schwan, P. , Maiser, B. , Niklas, J. , & Schembecker, G. (2015). Developing the biofacility of the future based on continuous processing and single-use technology. Journal of Biotechnology, 213, 120-130. https://doi.org/10.1016/j.jbiotec.2015.06.388. ; Lute, S. , Bailey, M. , Combs, J. , Sukumar, M. , & Brorson, K. (2007). Phage passage after extended processing in small-virus-retentive filters. Biotechnology and Applied Biochemistry, 47(3), 141-151. https://doi.org/10.1042/BA20060254. ; Orozco, R. , Godfrey, S. , Coffman, J. , Amarikwa, L. , Parker, S. , Hernandez, L. , Wachuku, C. , Mai, B. , Song, B. , Hoskatti, S. , Asong, J. , Shamlou, P. , Bardliving, C. , & Fiadeiro, M. (2017). Design, construction, and optimization of a novel, modular, and scalable incubation chamber for continuous viral inactivation. Biotechnology Progress, 33(4), 954-965. https://doi.org/10.1002/btpr.2442. ; Parker, S. , Amarikwa, L. , Vehar, K. , Orozco, R. , Godfrey, S. , Coffman, J. , Shamlou, P. , & Bardliving, C. (2018). Design of a novel continuous flow reactor for low pH viral inactivation. Biotechnology and Bioengineering, 115(3), 606-616. https://doi.org/10.1002/bit.26497. Contributed Indexing: Keywords: Dean vortices; continuous manufacturing; plug flow reactor; scale down; scale up; viral inactivation Entry Date(s): Date Created: 20210227 Date Completed: 20220302 Latest Revision: 20220302 Update Code: 20240513

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Utilizing bacteriophage to define the minimum residence time within a plug flow reactor.