The Modern Laboratory: Single use bioreactor technologies vs. traditional solutions

Issue 153 | November 19, 2021
13 min read
Capsid and Tail

This week, we’ve got a discussion on the advantages, disadvantages and comparative costs of single use bioreactors vs. traditional solutions, written by Adam Ostrowski, Technical Application Specialist at Cellexus.

Sponsor

Cellexus Sponsorship Logo

This issue was sponsored by Cellexus, which pioneers revolutionary, market leading single-use airlift bioreactor systems and technology.

Email enquiries@cellexus.com for more info.

What’s New

Erica Birkholz (University of California, San Diego) and colleagues published a new paper in bioRxiv showing a cytoskeletal vortex drives phage nucleus rotation during jumbo phage replication in E. coli.

Jumbo phageResearch paper

Fatima Aysha Hussain (Massachusetts Institute of Technology, Massachusetts) and colleagues published a new paper in Science showing rapid evolutionary turnover of mobile genetic elements drives bacterial resistance to phages.

Antibacterial resistanceMobile genetic elementsPhage resistanceResearch paper

Lore Van Espen (Katholieke Universiteit Leuven, Belgium) and colleagues published a new paper in mSystems showing a previously undescribed highly prevalent phage identified in a Danish enteric virome catalog

Research paperVirome

Rashedul Islama (Guelph Research and Development Centre, Canada) and colleagues published in Critical Reviews in Food Science and Nutrition a systematic review from basics to omics on bacteriophage applications in poultry production and processing.

Phage TherapyPhage in agricultureReview

Ying Liu (Institut Pasteur) and colleagues published a new paper in PLOS Biology on diversity, taxonomy, and evolution of archaeal viruses of the class Caudoviricetes.

Archaeal virusesResearch paper

Latest Jobs

Post Doc
The Pacific Northwest National Lab (Richland, WA) is hiring a Post Doctorate RA - Virome for a soil virome project related to bioenergy, carbon cycling & climate change.
Post Doc
The Talbert Lab at Iowa State University (Iowa, USA) is hiring a postdoctoral research associate to work on an NIH-funded project focused on bacteriophage engineering for therapeutic applications.
Post Doc
The Fischer Lab at the Max Planck Institute for Medical Research (Heidelberg, Germany) is hiring a postdoctoral researcher to investigate the infection biology, ecology and evolution of protist-specific viruses.
Post Doc
The Young Lab at the Centre of Phage Technology (Texas, USA) has post-doctoral and post-baccalaureate positions to study the molecular mechanisms of phage lysis.
Post Doc
The White Lab at the University of St Andrews (Scotland, UK) is hiring a postdoctoral research fellow to to study the molecular microbiology and the mechanism by which cyclic nucleotides are generated in response to viral/phage infection.
Clinical assay laboratory analyst
Clinical-stage biotech company, Adaptive Phage Therapeutics (APT)(Maryland, USA) is hiring a clinical assay laboratory analyst to conduct clinical testing of phage and assist in the conduct and reporting of clinical testing.

Community Board

Anyone can post a message to the phage community — and it could be anything from collaboration requests, post-doc searches, sequencing help — just ask!

New collaborator request on Instill, Phage Directory’s new structured peer feedback & collaboration platform:

Marwan M. Saleh has made a Collaboration Request:
“I’d like help making sure I’ve done my phage genome annotation correctly”

Help Marwan

Submit your own request

Instill ScienceSeeking collaborator

Many of us are excited for the upcoming Viruses of Microbes (VoM) conference finally taking place summer 2022 in Portugal (after being rescheduled from 2020). In collaboration, the International Society for Viruses of Microorganisms (ISVM), Phage Directory, and the organizers of VoM 2022 are excited to announce Season 2 of iVoM, a series of online lectures from prominent researchers studying viruses of microbes. Seven sessions will run from December 2021 to May 2022, in the lead-up to the exciting in-person version of VoM, July 2022.

The first iVoM2 event will be Dec. 8th at 12:00 PM (noon) CET, under the theme "Control on Viral Action: regulation of viral activity by other viruses and mobile genetic elements".

It will feature talks by:

  • Dr. Aude Bernheim, INSERM, France: “Systematic and quantitative view of the antiviral arsenal of prokaryotes”
  • Prof. Martin Polz, Univ. of Vienna, Austria: “The dynamics of bacterial innate defenses against phage”
  • Dr. Matthias Fischer, MPI for Medical Research, Germany: “The sleeper within - how endogenous virophages may defend protists against giant viruses”

Chair:

  • Corina Brussaard (Royal Netherlands Institute for Sea Research, Netherlands)

Register at https://ivom.phage.directory!

The rest of iVoM Season 2 will take place in 2022 and consist of six additional sessions (#2-7) on the topics of:

  1. Raiders of the third domain
  2. Phage application in the One Health approach
  3. Endless virus diversity most beautiful
  4. Environmental impact of virus-host interactions
  5. Models for viral action
  6. Personalised phage therapy
Virtual EventISVMPhage Directory

The Ibadan Bacteriophage Research Team, an undergraduate SEA-PHAGES team at the University of Ibadan, Nigeria announces the launch of its first journal issue PHAMILIA. The first undergraduate research journal in bacteriophage biology showcases student and faculty team members, as well as publications on diverse subjects of bacteriophage biology from the team and other guest writers.

New phage journal

Stephanie Lynch will chair the next Phage Phun session, which will be Thursday Nov 25 at 10AM AEST (Wed Nov 24, 3PM Pacific time). Join us for this informal virtual networking session by registering here. (If you’re already signed up for the PHAVES series or a past Phage Phun, no need to register again; we’ll send you the link closer to the date).

Phage phun!

Interested in contributing a blog post about your phage work (or your phage initiative) to C&T? Check out our Guest Writer Guide!

In keeping with our 4x per year draft submission deadline system, our next deadline is approaching!

  • For Jan-Mar, submit by Dec 1.
  • For Apr-June, submit by Mar 1.
  • For July-Sept, submit by June 1.
  • For Oct-Dec, submit by Sept 1.
Guest writingPhage Directory

The Modern Laboratory: Single use bioreactor technologies vs. traditional solutions

Profile Image
Technical Application Specialist
Cellexus, Dundee, United Kingdom
Twitter @AdamOstr
Skills

Biotechnology, Molecular Biology, Phage Therapy, Phage isolation

I’m a molecular microbiologist and I’ve spent my academic career investigating biofilm formation and later Type VI Secretion System and the molecular and biochemical workings of these systems. I then moved to industry research on development of phage-based treatments to extend the shelf life of fresh produce and finally I now work with Cellexus to help out the phage community grow phages at industrial scale using our CellMaker bioreactors. My job is to listen to your needs and find solutions using our tech, that you will enjoy. I also help existing customers with equipment training and operations.

Every development process in an innovative biotechnology or biopharmaceutical plant has an identical goal: to bring a new bio-based product to market while taking into account acceptable costs and maximizing profits. One of the biggest sources of the cost of goods is the production process itself, and therefore also the type of technology used in this process.

Traditional bioproduction plants rely on stainless steel (SS) fermenters with large capacities (20,000 L or more) and related downstream processing equipment. In the mid-2000s, the dominant status of the reusable bioprocess technologies encountered competition from the first single use (SU) fermenters.

At this point, a dilemma emerged as to which type of technology to choose, and which one would be the most efficient and suitable for a given bioprocess. Although disposable fermentation systems are still very limited in scale compared to stainless steel systems (the largest disposable systems currently reach around 5,000 L), they are more often used as equipment in innovative biotechnology labs than difficult to use and expensive to upkeep SS systems.

As a representative of a manufacturer of SU systems, the first question I encounter most often is how to compare the costs of SU systems to more traditional reusable solutions. Undoubtedly, anyone considering switching to a SU system immediately notices the cost of consumables. Mostly, they indicate that these costs are very high, and fermentation in a steel bioreactor requires virtually no operating costs. They also say that the disposable materials generate huge amounts of waste. This reaction is perfectly logical and understandable; however, the reality is surprisingly much more complex.

Compared to SS solutions, the main advantage of the SU technology is the absence of cleaning and sterilization in place (CIP/SIP) normally required between processes in each of the SS devices. This routine activity takes a long time and requires the instruments to be turned off, frequently for several days at a time and requires the system to be certified for sterility prior to being used again. Switching to a SU system, CIP is minimal, SIP is entirely removed, and the duty of sterility validation is transferred from the operator to the equipment manufacturer.

In addition, SU technologies allow for a much greater scope for adapting the laboratory to conduct various bioprocesses, excluding the danger of cross-contamination. For example, a bioprocessing laboratory outfitted with reusable equipment is usually dedicated to only one type of bioproduct, therefore, the production of various preparations requires construction of multiple production lines.

On the other hand, using SU technologies we can completely replace all components of the production line, which come in contact with the process, with new ones, and thus completely separate the processes despite using the same equipment. By avoiding the cleaning of equipment between batches, we also save on staff work time, who can focus on the production instead of equipment maintenance.

The costs and profits analysis of SS and SU technologies is also very interesting. The highest costs of SS technology are the cost of purchase and installation, followed by the cost of CIP/SIP [1], including labour time and costs. SU solutions have significantly lower capital costs, up to 40% [2, 3], and a much faster lead time for delivery of capital equipment, which allows for more time to make the final decision on which particular SU solution will be used in the newly created laboratory or processing plant. In addition, SU systems reduce operating costs by up to 20% and employee costs by a further 10% [4]. Of course, these costs are partly offset by high consumables prices, however, on balance the costs of the energy required to maintain a SS system outstrips the consumable costs of SU.

The potential profits should also be considered in the above calculations, as well as costs of goods. For example, according to a recent study, the profits from the production of 2000 L of monoclonal antibody suspension in a SS system in comparison to a SU system, in which not only the bioreactor system was replaced with a SU solution but also the centrifuges were replaced by filtration systems, the SU system generated 91kg of bioproduct at a total cost of 70 Euro/g. The SS system, on the other hand, yielded only 87kg of product with a cost of 102 Euro/g [2]. According to the authors of this study, the main sources of difference in the cost of goods are the product losses during downstream processing and the maintenance costs of the reusable equipment, including chemicals and deionized water used for CIP/SIP.

Reusable technologies.png
single use technologies.png
Figure 1. Proportional comparison of costs of product using single use or reusable technologies at production scale of 3000 kg of bioproduct per year. Based on Mahal et al. (2021).

In addition to financial costs, environmental costs are also inevitable in any bioprocess. SU technologies generate large amounts of plastic waste. Their presence is very visible, and the sizes can be overwhelming. However, a well-managed bioprocess plant can use the services of incineration plants, where some of the energy used for the production of consumables can be recovered as heat from incineration of the waste material [5]. In addition, the cost of energy, highly toxic chemicals necessary for CIP/SIP processes, their disposal and production of deionized water necessary for cleaning of the machinery, is often hidden in indirect costs. These can amount to even 13% of the total production costs on a scale of 3000 kg of the product per year or even more at smaller production scales. In comparison, the cost of combustion of the SU consumables can be significantly lower than the CIP/SIP costs [1,3,5].

In summary, the answer to the question of which technology to choose, reusable or disposable, is not a straightforward one. Such a decision should be based on the type of bioprocess being performed, the certification requirements and the needs of the bioprocessing plant. When choosing an SU technology provider, we choose not only a contractor, but also a partner for a long period. The SS solution provider, similarly, should be able to guarantee long-term service of the equipment. Undoubtedly, however, SU technologies are more flexible and adaptable, and particularly useful where the ability to quickly switch to new requirements is crucial, and your equipment is used for a wide range of applications both upstream and downstream.

CellMaker image.jpg
The Cellexus CellMaker.

Brian in Poland - Proteon Lab.jpeg
Proteon Pharma’s lab, which features Cellexus CellMakers.

References

  1. Mahal, H., Branton, H. & Farid, S. S. End-to-end continuous bioprocessing: Impact on facility design, cost of goods, and cost of development for monoclonal antibodies. Biotechnol. Bioeng. bit.27774 (2021) doi:10.1002/bit.27774.

  2. Gupta, P., Monge, M., Boulais, A., Chopra, N. & Hutchinson, N. Single‐Use Process Platforms for Responsive and Cost‐Effective Manufacturing. in Single‐Use Technology in Biopharmaceutical Manufacture 201-210 (Wiley, 2019). doi:10.1002/9781119477891.ch16.

  3. Guldager, N. Cost advantages of single use technologies. Pharm. Technol. 34, 26-31 (2010).

  4. Lütke-Eversloh, T. & Rogge, P. Biopharmaceutical manufacturing in single-use bioreactors current status and challenges from a CDMO perspective . Pharm. Ind. 80, 281-284 (2018).

  5. Flanagan, W. et al.  An Environmental Lifecycle Assessment of Single-Use and Conventional Process Technology: Comprehensive Environmental Impacts. BioPharm Int. 27, 40-46 (2014).


Many thanks to Stephanie Lynch, Atif Khan and Tolulope Oduselu for finding and summarizing this week’s phage news, jobs and community posts!

Capsid & Tail

Follow Capsid & Tail, the periodical that reports the latest news from the phage therapy and research community.

We send Phage Alerts to the community when doctors require phages to treat their patient’s infections. If you need phages, please email us.

In collaboration with

Mary Ann Liebert PHAGE

Supported by

Leona M. and Harry B. Helmsley Charitable Trust

Crossref Member Badge