Thermo scientific offers a range of bioreactors perfectly suited for mammalian cell culture and microbial fermentation applications that span process development, clinical trials, and large scale commercial biomanufacturing. Table 1 lists common needs and expectations related to scale up of cell culture bioreactors that industryoriented bioengineers frequently mention. Bench scale bioreactors ranging in volume from about 2 l to 20 l. This experiment demonstrates how a robotically controlled microbioreactor system can be combined with doe methods to optimize cellculture media and feeding. The cell culture sterilizableinplace bioreactor systems come in a total volume of 30 liter, 60 liter and liter. Bionet is the right partner to deliver the bioreactor you need for the successful industrial scale up of your cell culture or fermentation processes. Thermo fisher scientific prioritizes scale up aspects of its singleuse systems, including bioprocess containers, and its controllers and software are identical for labscale and largescale cgmp production. This bioreactor provid es a sufficient surface f or the large scale. Cellscales bioreactors provide insights into the response of cells and tissues to mechanical stimulation. When leaving the lab and designing your industrial solutions numerous challenges have to be solved. The multifors 2 is a compact, freestanding device with up to six culture vessels on three base units.
Bioprocess engineers must keep track of recent trends and consider various aspects, such as scale up capabilities, control strategies and automation, and validation requirements. Apr 22, 2005 large scale cell culture came of age with the success of highdose, chronically administered monoclonal antibodies mabs. The bioreactor will be scaled up by a factor of 125. Most often, initial experiments are performed using shake flasks but the conditions in the small scale bioreactor differ significantly from the shake flask. Cellculture advances test bioreactor performance models. Xdr bioreactor systems offer the following benefits. A new single use bioreactor for small scale cell cultures. The entire assembly can be sterilized and is suitable for longterm cell culture in a laboratory incubator. Cell culture scaleup in stirredtank singleuse bioreactors. Moreover, since realtime monitoring and control is not possible in a shaker, eventual process transfer and scaling up are indispensable measures.
The labfors 5 cell is always application optimized for your cell culture bioprocess. Compared with batch processing, it has the potential to enable. This white paper examines a unique, compacttransmitter system for bioreactor manufacturers to support scaleup from the laboratory scale to the production scale as well as the reverse. This design is stated to create separate cell growth and aeration zones. Newly emerging technologies should enhance cell culture process development, scaleup, and process control significantly. Applications data support solutions to overcome your cell culture scale up challenges ge is dedicated to developing resources to help address. Scaleup considerations for monoclonal antibody production. Singleuse technology and support for solving your biomanufacturing challenges achieving the delicate balance of product quantity, quality. It is suitable for multiple applications but is especially well suited for seed train operations for the icellis bioreactor as well as for. Classic stirredtank design ensures seamless scale conversion to the biostat str singleuse bioreactor and also to stainless steel equipment for largescale manufacturing. Multifors 2 parallel bioreactor system for smallscale. The data for a smallscale bioreactor are a 100 litres fermenter with 187.
Cellscale mechanoculture b1 biaxial stretching on a. Everything you ever wanted to know about cell culture process. In addition, the software is intuitive and easy to use. The labfors 5 cell is a leading benchtop bioreactor, providing the user with an easy to handle, flexible and upgradeable system for culture volumes from 0. Typical applications range from smallscale protein expression to media or process optimization studies. Applikon offers tailormade and fully reproducible solutions with 500 ml and 3 l singleuse bioreactors. Bioprocess scaleup in cell culture industry is a task, still based on historical. Its size and the ability to preprogram the bioreactor conditions results in a costeffective solution to our bioreactor needs.
To give you more flexibility in the lab, we have organized the vessels into groups of two that you can separate, recombine or expand. Scaleup involves the development of culture systems in stages from small scale laboratory to large scale industry. The systems support specimens up to 10mm wide and 80mm long. Fundamentals of bioreactor design are the following functions. Scale up of bioreactor systems prathibha narayanan. Parallel processing, precise control of all relevant parameters, userdefined profiles, and innumerable automation features result in accelerated and highly efficient process development.
Aug 14, 2015 requirements for a bioreactor for animal cell culture 1 wellcontrolled environment t, ph, do, nutrients, and wastes 2 supply of nutrients 3 gentle mixing avoid shear damage to cells 4 gentle aeration add oxygen slowly to the culture medium, but avoid the formation of large bubbles which can damage cells on contact. Automatic control of ph is maintained via base addition and co. These challenges are cell line and process specific. Once these are applied in combination with highperforming, singleuse bioreactors, then extremely high cell densities will become a reality. Modular design enables configurability and provides added flexibility. He managed cell culture bioprocessing in both singleuse and conventional stirred tank bioreactors. Based on experimental results, the software identified a set of optimal values for each factor left side of figure 5, resulting in a desirability value of 0. Oct 01, 2009 based on experimental results, the software identified a set of optimal values for each factor left side of figure 5, resulting in a desirability value of 0. Tffuf is tangential flow filtrationultrafiltration. Most often, initial experiments are performed using shake flasks but the conditions in the small scale bioreactor differ. Largescale mammalian and insect cell culturing and large. When making the transition from conventional dishbased cell culture to bioreactors, it can be less daunting to start with smaller vessels and scale up if needed, after conditions are optimized. New applications such as stem cell cultivation may evolve to powerful tools in the future. A singleuse vessel option adds further flexibility.
Xcellerex xdr singleuse bioreactor systems provide scalable and robust stirredtank performance for up to 2000 l in both cgmp and noncgmp environments. The thermo scientific hyperforma singleuse bioreactor s. Doe helps optimize a cell culture bioproduction system. Scaleup of cell culture bioreactors using biomechatronic design. Jun 29, 2017 thermo fisher scientific prioritizes scale up aspects of its singleuse systems, including bioprocess containers, and its controllers and software are identical for labscale and largescale cgmp production. For overcoming the above difficulty and to facilitate scale up of plant cell culture bioreactor a design of low shear bioreactor has been reported.
Optimization of lentiviral vector production for scaleup in. In one case, a bioreactor is a vessel in which a chemical process is carried out which involves organisms or biochemically active substances derived from such organisms. Jul 14, 2014 when making the transition from conventional dishbased cell culture to bioreactors, it can be less daunting to start with smaller vessels and scale up if needed, after conditions are optimized. Moreover, since realtime monitoring and control is not possible in a shaker, eventual process transfer and scalingup are. Continuous cell culture operation at 2,000l scale michael sherman, vincent lam, melissa carpio, nick hutchinson, and christel fenge. The bioreactor controls temperature, agitation, ph and dissolved oxygen. This chapter comprises engineering aspects of bioreactor systems design, operation, scaleup developed or adapted for cultivation of mammalian cells, such as bioreactors for suspension culture stirredtank reactors, bubble columns, and airlift reactors, fixed bed and fluidized bed reactors, hollow fiber and membrane reactors, and, finally. Mammalian cell culture bioprocesses are increasingly gaining. Cell culture scale up purification chromatography buffer operations bulk storage fig 1.
Overcoming scaleup challenges during culture media. In this article, a new approach for cell culture bioreactor scale up is suggested that is b ased on biomechatronic design methodology. Cell expansion for inoculating the 333 m 2 bioreactor could be carried out in large scale 2d cell culture vessels, available, for example, in sizes of 1720 cm 2. A major factor impacting bioreactor system scalability is the availability of consistent inline measurement.
Thanks to a selection of preconfigured packages and a variety of connection possibilities and options, you will be ideally equipped for optimizing sophisticated bioprocesses on a small scale. Nov 21, 2019 mammalian cell culture bioprocesses are increasingly gaining importance in the biopharmaceutical industry. Cell culture process performance at 2 l, 10 l and 80 l scale. Eppendorf bioblu singleuse vessels for cell culture scaleup from small to pilot scale. Introduction animal cell culture is the process of culturing animal cells outside the tissue in vitro. Optimally suited for production of mabs, vaccines, recombinant proteins and in cell and gene therapy applications, the systems support many different types of cell lines and processes including. The choice of bioreactor for cell culture is often decided based on. Scale up of cell culture bioreactors is a challenging engineering work that requires wide competence in cell biology, mechanical engineering and bioprocess design. Scale up of cell culture bioreactors using biomechatronic. Everything you ever wanted to know about cell culture. Due to the high demand of product quality, the incubated shaker as a production unit can become a limiting factor after a certain point. The m80 sm transmitter optimizes bioreactor system scalability by providing consistent inline measurement for all reactor sizes. Using doe with micro bioreactor improves process control for scaling up cell cultures june 7, 2019 finding a better way to scale up commonly used research cells like hek293t used for protein expression and the production of recombinant retroviruses or l entiviral vectors would be beneficial for biologists in many fields of medicine. Perfusion, or upstream continuous bioprocessing, has been practiced in cell culture since the 1980s but with limited adoption.
Comprehensive study on wave bioreactor system to scale up. Mammalian cell culture bioprocesses are increasingly gaining importance in the biopharmaceutical industry. In this webinar, we discuss several scaling approaches, such as constant tip speed, kla, and power numberbased scale up. A bioreactor refers to any manufactured device or system that supports a biologically active environment. Dasgip parallel bioreactor systems bioprocess systems. Open architecture singleuse bioreactors thermo fisher. The wheaton mini pilot plant spinner flask system is a large volume cell culture bioreactor designed to scale cultures up to production volumes of cells or products. Scaleup analysis for a cho cell culture process in largescale. Typically, benchtop bioreactors are operated in the performance design space of larger bioreactors to model scale up performance, according to parrish m.
Newly emerging technologies should enhance cell culture process development, scale up, and process control significantly. Experimental results revealed that, although the specific protein expression was not affected upon scaleup, final cell density was a bit lower 2. Add in challenges such as validation of new cell culture media or changes in scale, and this balance can seem just out of reach. With the appliflex st singleuse mini bioreactor, we provide the same flexibility of our customizable range of glass and stainlesssteel bioreactor systems to the singleuse lab scale bioreactor market. In this webinar, we discuss several scaling approaches, such as constant tip speed, kla, and power numberbased scaleup. Experimental setup the overall experimental setup, including both cell bank and seed culture generation, is provided in figure 2 and.
Xdr bioreactor systems can be operated in batch, fed. Scaleup of cell culture bioreactors using biomechatronic. The singleuse system can be exchanged with a glass multiuse system whenever your process or workflow needs a different approach. The emergence of a variety of geometrically dissimilar singleuse bioreactor platforms provides users with both challenges and opportunities as they look to. The scaleup process is divided into two categories. Cellscale also has extensive experience in developing custom solutions that exceed expectations. While the number of cell culture processes with 10,000l, 20,000l, and higher capacities is growing, most cell cultures are smallish operations ranging from a few hundred mls to several thousand liters of working volume.
Bioprocess engineers must keep track of recent trends and consider various aspects, such as scaleup capabilities, control strategies and automation, and validation requirements. Using doe with micro bioreactor improves process control for. Separation of gas and electrical power for enhanced safety scalable and predictable stirred. Other potential pitfalls include not accounting for changes in bioreactor performance as a function.
Comprehensive study on wave bioreactor system to scale up the. In continuous bioprocessing, pilot scaleup is a key transitional step. Two cases are presented here to illustrate the variety of situations encountered during initial scaleup from shaker flask culture to benchscale bioreactor culture and cell line 2. With multifors 2 you can work with up to six bioprocesses in parallel. The cellscale mechanoculture has been a very versatile bioreactor platform for us. Increasing use of innovative technologies, turnkey systems, cell culture supplements and singleuse assemblies has changed the paradigm, making perfusion cell culture a viable platform for continuous processing. Adaptable to a variety of molecules, applications, or multidrug processes. Bioreactor scalability is critical to streamlining the adaptation of culture volumes during process development and manufacturing. Singleuse technology and support for solving your biomanufacturing challenges achieving the delicate balance of product quantity, quality, cost, and speed is difficult in dynamic circumstances. Sartorius the univessel su is suitable for mammalian, insect and plant cell culture in scales up to two liters volume.
Sartorius stedim biotech supplies the widest range of cell culture bioreactors for research and development work through to pilot and cgmp manufacture. Continuous cell culture operation at 2,000l scale michael sherman, vincent lam, melissa carpio, nick hutchinson, and christel fenge i n the biopharmaceutical industry, continuous manufacturing is often cited as a method for increasing the productivity of bioprocesses 1. It will continue to grow if supplied with appropriate. We have systems optimized for highthroughput, realtime imaging, 3d scaffold use, and multimodal stimulation. Scaleup of cell clarification operations for much higher cell masses 30m. Advanced analytical capabilities including online glucose and lactate measurement, offgas measurement and viable biomass cell density measurement allow predictive process. Galliher, chief technical officer for upstream and founder of xcellerex, a ge healthcare life sciences business. Typical applications range from small scale protein expression to media or process optimization studies. Criteria for scaleup and scaledown of bioreactors for cultivation of. Table 1 lists common needs and expectations related to scaleup of cell culture bioreactors that industryoriented bioengineers frequently mention. The data for a small scale bioreactor are a 100 litres fermenter with 187. A number of benchtop mini or microbioreactors are available that incorporate sensors and use software to optimize conditions. The xpansion multiplate bioreactor system is a closed, singleuse system that has been specifically designed for the scale up of shearsensitive, adherent mammalian cells under controlled conditions. The design of the appliflex st is a scale down version of our larger laboratory scale systems, guaranteeing an easy scale up of your process starting at 500 ml and upwards.
The small scale bioreactor is most similar to in situ conditions for cell growth because it can be monitored and optimized throughout a run. Optimizing bioprocess scaleup from milligrams to kilograms. The allegro xrs 25 bioreactor system is a singleuse bioreactor system with unique agitation and control properties designed for the cultivation of mammalian cells in suspension culture under controlled conditions. Scaling up your cell cultures to bioreactors biocompare. Cellscale mechanoculture t6 bioreactor for fibrelike. The system can also be adapted to wider sheetlike specimens and fiber specimens.
The thermo scientific hyperforma rocker bioreactor is controlled by the hyperforma g3lab controller and trubio software, providing a complete, readytouse solution. This means that your software can tell you if conditions inside the bioreactor start to take a divebefore you lose your entire culture, and perhaps. The main difference between these two lines is the aspect ratio of the bioreactors. Xcellerex xdr 50 to 2000 singleuse stirredtank bioreactors. In this study, cellfree mixing studies were performed in production scale 5,000l bioreactors to evaluate scaleup issues. Bristolmyers squibb largescale cell culture biologics manufacturing facility project.
Unique biaxial agitation improves cell culture performance. Bionet is the right partner to deliver the bioreactor you need for the successful industrial scaleup of your cell culture or fermentation processes. It is necessary to discuss the effect of operating variables resulting from constant power per unit volume, agitation rate, and speed tip velocity, n re. Using doe with micro bioreactor improves process control. Largescale cell culture came of age with the success of highdose, chronically administered monoclonal antibodies mabs. The bioreactor portfolio offers options from 1 l glass bioreactors to 2,000 l singleuse bioreactors. Pavel k scaleup and down modeling of bioreactors is a valuable tool to support process characterization and improvement in a predictable, timely, and costeffective manner.
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