Design and characterization of a novel perfusion reactor for biopharmaceuticals production

Tregidgo, Molly; Dorn, Marie; Lucas, Ciara; Martina, Micheletti

doi:10.1016/j.cherd.2023.04.066

Cited by 4 publications

(7 citation statements)

References 38 publications

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“…The biggest number of previously published papers, which included the colourimetric method for determination of mixing time, regarded stirred tank reactors and bioreactors, including, in some cases, single-use bioreactors [34][35][36]. The investigations included baffled and unbaffled classical tanks agitated with various equipment: Rushton turbines [3,10,[15][16][17]19,24,25,27,28,[31][32][33] and their variants (Scaba SRGT [15]), pitchedblade impellers [3,10,17,24,25,33], disk turbines [19], elephant ear [27,36] and marine blade impellers [27,34,35], hydrofoil [14], Maxblend™ [10,22,23], helical ribbon [13,18,29], a trapezoidal paddle [30], axial flow impellers [24] and planetary [18,21] and coaxial mixers [20]. Some papers contained results from experiments involving orbitally shaken devices, i.e., shake flasks [6], orbitally-shaken single-use bioreactors [37,38,…”

Section: Applications Of the Colourimetric Methods Across Types Of De...mentioning

confidence: 99%

“…Typically, the maximum volume of the vessel analysed using the colourimetric method was no larger than 1000 L. The volume of analysed vessels ranged from the millilitre scale [6,27,30,33,38,44], including vessels from parallel bioreactor systems [35], through bench-scale and laboratory-scale devices [16][17][18][20][21][22]24,[27][28][29]31,32,34,36,37], up to pilotscale systems in the hundred-litre range [14,15,19,22,24,25]. However, one has to note the examples of large-scale reactors, such as the 1500 L orbitally shaken single-use plastic filmbased bag-like container analysed by Tissot et al [37] or the 15 m 3 stirred tank investigated by Rosseburg et al [3].…”

Section: Applications Of the Colourimetric Methods Across Types Of De...mentioning

confidence: 99%

“…An example is the case of single-use bioreactors, where the culture bag is made from multilayer plastic film [51] or, as in small-scale stirred SUBs [34,35], from rigid plastic material. Sources also report the use of vessels made from glass [2,16,21,24,26,28,31,43,48], acrylic/plexiglass [3,13,15,24,25,33,36,52] or polycarbonate [10,19,53].…”

Section: Properties Of the Device For Characterisationmentioning

confidence: 99%

“…The choice of filming equipment depends primarily on its availability, cost, the desired size in relation to the experimental setup and existing inventory and expertise inside a research facility. The literature contains reports of the use of industrial solutions [6,30,33,36,40,44] or consumer-grade devices such as digital SLRs [27,28,31,57], mirrorless [45] or compact digital cameras [26,29,32,37,38] or webcams [18]. Other consumer equipment could be suitable for a colourimetric method setup, including action cameras or widely available smartphone cameras.…”

Section: Filming Equipment (Camera Lighting)mentioning

confidence: 99%

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The Colourimetric Method for Mixing Time Measurement in Single-Use and Multi-Use Bioreactors—Methodology Overview and Practical Recommendations

Bartczak,

Pilarek

2023

Energies

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Mixing time is an important parameter for quantifying the mixing efficiency of a bioreactor system, essential for successful bioprocess development in various branches of the bioengineering sector (e.g., biopharma, biorefineries, food industry and bioreactor design). The colourimetric method is one of the ways of obtaining valuable quantitative data about the mixing process and the liquid flow inside a vessel. This review consists of a catalogue and a discussion of previously published data in which the colourimetric method has been utilised; a critical comparison between the colourimetric and other mixing time measurement methods; an explanation of practical considerations regarding the bioreactor setup and the choice of reagents; a practical guide for requirements for the acquisition of high-quality images of the mixing process; a thorough discussion of aspects connected to the computer image processing of the video material. This review is intended to thoroughly present the versatility of the colourimetric method for mixing time measurement in miscellaneous bioreactor systems, i.e., in classical tanks and modern single-use (disposable) plastic film-based bag-like containers, and to facilitate the implementation of the colourimetric method in new research setups by providing complete and valuable recommendations about each step of the methodology.

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Section: Applications Of the Colourimetric Methods Across Types Of De...mentioning

confidence: 99%

Section: Applications Of the Colourimetric Methods Across Types Of De...mentioning

confidence: 99%

Section: Properties Of the Device For Characterisationmentioning

confidence: 99%

Section: Filming Equipment (Camera Lighting)mentioning

confidence: 99%

See 2 more Smart Citations

The Colourimetric Method for Mixing Time Measurement in Single-Use and Multi-Use Bioreactors—Methodology Overview and Practical Recommendations

Bartczak,

Pilarek

2023

Energies

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“…High volumetric mass transfer coefficients (k L a values) were often not necessary for mammalian-cell-based production processes, since only low VCDs were achieved in these fed-batch processes. Consequently, cell culture bioreactors have been designed in such a way that axial pumping stirrers ensure good mixing at low stirrer speeds and low specific power inputs, because the avoidance of high shear forces in the cultivation of mammalian cells was a major concern for a long time [16,17]. However, various studies have shown that CHO cells can be successfully cultivated at high specific power inputs of up to 4700 W m −3 using radial pumping stirrers which are classically used in microbial bioreactors [18][19][20], indicating that the tolerance range of the cells to shear forces is quite high.…”

Section: Introductionmentioning

confidence: 99%

Scaling Fed-Batch and Perfusion Antibody Production Processes in Geometrically Dissimilar Stirred Bioreactors

Ott,

Eibl

et al. 2024

Processes

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Modern production processes for biopharmaceuticals often work with very high cell densities. Moreover, there is a trend towards moving from fed-batch to continuous perfusion processes; a development that is influencing the requirements for bioreactor design and process control. In this study, the transfer of fed-batch and perfusion experiments between different cylindrical stirred lab-scale bioreactors and Thermo Scientific’sTM (Waltham, MA, USA) cubical HyPerformaTM DynaDriveTM Single-Use Bioreactor was investigated. Different scaling parameters were used, which were selected based on the requirements of the respective processes. Peak cell densities of up to 49 × 106 cells mL−1 and antibody titers of up to 5.2 g L−1 were achieved in 15- to 16-day fed-batch experiments. In 50-day perfusion cultivations, a viable cell volume of >100 mm3 mL−1 was maintained and more than 1 g L−1 d−1 of antibodies were harvested. The perfusion processes were automated with both cell bleed control and glucose concentration control. Cell retention was performed using Repligen’s (Waltham, MA, USA) XCell® ATF perfusion systems and single-use devices. In summary, approaches for successfully scaling highly productive fed-batch and perfusion processes between geometrically dissimilar lab and pilot scale bioreactors were demonstrated. The advantages of perfusion in comparison to fed-batch processes were also observed.

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Two scale‐down tools for the optimization of perfusion bioreactors for the manufacture of biopharmaceuticals

Lucas,

Blackman,

Rayat

et al. 2024

J Adv Manuf & Process

Self Cite

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As the occurrences of cancer rise and the requirement for biotherapeutics increases, there is a growing demand for cost‐efficient methods to manufacture mammalian cell‐based biopharmaceuticals. Currently, the most cost‐efficient manufacturing solution is the cultivation of cells in perfusion mode. Perfusion allows for high cell densities of up to 200 million viable cells per mL (MVC mL−1) to be achieved, resulting in an increase in yield and volumetric productivity, which is the production of product per unit volume and time. However, culturing in perfusion mode requires large volumes of media, which is a significant expense in process development. Therefore, methods that allow rapid optimization of perfusion media are desirable to decrease operating costs and increase productivity. In this work, a quasi‐perfusion methodology using microwell plates (MWP) is used for media optimization to culture CHO‐S cells producing IgG1 monoclonal antibodies (mAb) known as trastuzumab, which have clinical applications treating HER2+ breast cancer. Results show blending glucose‐rich supplements and sodium butyrate with perfusion‐specific base media can lead to an 8‐fold increase in monoclonal antibody titre compared with traditional fed‐batch media. The original and optimized media were then scaled‐up to a custom made, mini bioreactor (MBR) running in perfusion mode. Two‐fold higher cell density is achieved in the MBR compared with the MWP, however, when normalizing for cell density, mAb productivity is comparable between the two methodologies. The combined MWP and 250 mL MBR methodology is an optimization tool that enables process development cost savings due to reduced volume of media utilization.

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Design and characterization of a novel perfusion reactor for biopharmaceuticals production

Cited by 4 publications

References 38 publications

The Colourimetric Method for Mixing Time Measurement in Single-Use and Multi-Use Bioreactors—Methodology Overview and Practical Recommendations

The Colourimetric Method for Mixing Time Measurement in Single-Use and Multi-Use Bioreactors—Methodology Overview and Practical Recommendations

Scaling Fed-Batch and Perfusion Antibody Production Processes in Geometrically Dissimilar Stirred Bioreactors

Two scale‐down tools for the optimization of perfusion bioreactors for the manufacture of biopharmaceuticals

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