Development of a transportable single-use biomanufacturing system for therapeutic phage preparations Article Swipe
Maia Merabishvili
,
Hilde Van Raemdonck
,
S. Cencig
,
Gunther Verween
,
Peter Corte
,
B. Pascual
,
Gilbert Verbeken
,
J. P. Draye
,
Tyler Rose
,
Serge Jennes
,
Mario Vaneechoutte
,
Daniël De Vos
,
Jean‐Paul Pirnay
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1016/j.ijid.2018.04.3748
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1016/j.ijid.2018.04.3748
Background: The worldwide antibiotic crisis has led to a renewed interest in phage therapy. Lytic phages against bacterial pathogens can be isolated from the environment or selected from a collection in a matter of days. Product discovery costs are very low, but conventional biopharmaceutical production of phages is lengthy, complex and costly. In addition, phage treatment in low-income countries with poor infrastructure, battlefields, healthcare emergency situations (e.g. the 2012 foodborne E. coli 0104:H4 outbreak in Germany) demands a fast, global and decentralized access to phages. To address this demand, we developed a single-use, pre-sterilised, portable and closed biomanufacturing platform for therapeutic phage preparations. Methods & Materials: The basic components of this platform are as follows: a stacked bioreactor vessel with an adaptable number of chambers, in which the host bacterial strain, phage seed, culture medium (soft agar overlay technique) and extraction buffer are injected, is connected to (a) a cascade of clarification, purification and sterilisation filters, (b) phage vent filters, (c) tubings and connectors and (d) a filling system to dispense the final phage suspension into recipients. The following devices are necessary: a peristaltic pump, a fridge, a shaker and an incubator. Twenty-four different prototype assemblies for the production of Pseudomonas aeruginosa phages were tested. The following parameters were measured: pressure in function of volumetric throughput, phage yield and titre, endotoxin level, pH and assembly integrity (leaks). Results: The most suitable of the 24 tested prototype assemblies (presented at the conference) allowed for the production of 1-200 L (per bioreactor chamber) of phage suspension at a concentration of 107 pfu/ml with endotoxin levels and pH compatible with intravenous (IV) application, and this in 24 to 36 h. Conclusion: We developed a small-scale, portable and disposable biomanufacturing platform that allows for bacterial infection treatment at point-of-care, in short time frames, and at low cost, especially useful in remote locations with limited infrastructure since it does not necessarily require a cleanroom environment. MM and HVR contributed equally to this work. Funding: Grant HFM 15-5 of the Royal Higher Institute for Defense.
Related Topics
Concepts
Biomanufacturing
Phage therapy
Microbiology
Peristaltic pump
Biology
Bacteriophage
Biotechnology
Engineering
Escherichia coli
Mechanical engineering
Gene
Biochemistry
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.ijid.2018.04.3748
- OA Status
- gold
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2883440966
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2883440966Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.ijid.2018.04.3748Digital Object Identifier
- Title
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Development of a transportable single-use biomanufacturing system for therapeutic phage preparationsWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2018Year of publication
- Publication date
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2018-07-27Full publication date if available
- Authors
-
Maia Merabishvili, Hilde Van Raemdonck, S. Cencig, Gunther Verween, Peter Corte, B. Pascual, Gilbert Verbeken, J. P. Draye, Tyler Rose, Serge Jennes, Mario Vaneechoutte, Daniël De Vos, Jean‐Paul PirnayList of authors in order
- Landing page
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https://doi.org/10.1016/j.ijid.2018.04.3748Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1016/j.ijid.2018.04.3748Direct OA link when available
- Concepts
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Biomanufacturing, Phage therapy, Microbiology, Peristaltic pump, Biology, Bacteriophage, Biotechnology, Engineering, Escherichia coli, Mechanical engineering, Gene, BiochemistryTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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