Cell culture bioreactor scale up software

In this study, cellfree mixing studies were performed in production scale 5,000l bioreactors to evaluate scaleup issues. Bionet is the right partner to deliver the bioreactor you need for the successful industrial scaleup of your cell culture or fermentation processes. Eppendorf bioblu singleuse vessels for cell culture scaleup from small to pilot scale. Moreover, since realtime monitoring and control is not possible in a shaker, eventual process transfer and scaling up are indispensable measures. 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 cellscale mechanoculture has been a very versatile bioreactor platform for us. 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. Moreover, since realtime monitoring and control is not possible in a shaker, eventual process transfer and scalingup are. Overcoming scaleup challenges during culture media. Scaleup of cell culture bioreactors using biomechatronic. Separation of gas and electrical power for enhanced safety scalable and predictable stirred. Automatic control of ph is maintained via base addition and co. Experimental setup the overall experimental setup, including both cell bank and seed culture generation, is provided in figure 2 and. 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. 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.

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. The bioreactor portfolio offers options from 1 l glass bioreactors to 2,000 l singleuse bioreactors. A bioreactor refers to any manufactured device or system that supports a biologically active environment. When leaving the lab and designing your industrial solutions numerous challenges have to be solved. 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. Add in challenges such as validation of new cell culture media or changes in scale, and this balance can seem just out of reach.

Introduction animal cell culture is the process of culturing animal cells outside the tissue in vitro. 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. Sartorius the univessel su is suitable for mammalian, insect and plant cell culture in scales up to two liters volume. 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. Bioprocess scaleup in cell culture industry is a task, still based on historical. 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. Scaleup involves the development of culture systems in stages from small scale laboratory to large scale industry. Open architecture singleuse bioreactors thermo fisher. Xdr bioreactor systems can be operated in batch, fed. Bioprocess engineers must keep track of recent trends and consider various aspects, such as scaleup capabilities, control strategies and automation, and validation requirements.

Modular design enables configurability and provides added flexibility. 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 data for a smallscale bioreactor are a 100 litres fermenter with 187. Classic stirredtank design ensures seamless scale conversion to the biostat str singleuse bioreactor and also to stainless steel equipment for largescale manufacturing. 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.

Scale up of cell culture bioreactors using biomechatronic. Galliher, chief technical officer for upstream and founder of xcellerex, a ge healthcare life sciences business. A major factor impacting bioreactor system scalability is the availability of consistent inline measurement. 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 considerations for monoclonal antibody production. Bench scale bioreactors ranging in volume from about 2 l to 20 l. 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.

The cell culture sterilizableinplace bioreactor systems come in a total volume of 30 liter, 60 liter and liter. New applications such as stem cell cultivation may evolve to powerful tools in the future. 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. Bioprocess engineers must keep track of recent trends and consider various aspects, such as scale up capabilities, control strategies and automation, and validation requirements. A new single use bioreactor for small scale cell cultures. 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.

It is suitable for multiple applications but is especially well suited for seed train operations for the icellis bioreactor as well as for. Adaptable to a variety of molecules, applications, or multidrug processes. The emergence of a variety of geometrically dissimilar singleuse bioreactor platforms provides users with both challenges and opportunities as they look to. 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. Experimental results revealed that, although the specific protein expression was not affected upon scaleup, final cell density was a bit lower 2. The bioreactor will be scaled up by a factor of 125. Compared with batch processing, it has the potential to enable. 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.

Cellculture advances test bioreactor performance models. 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. 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. Newly emerging technologies should enhance cell culture process development, scale up, and process control significantly. 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. In addition, the software is intuitive and easy to use. Apr 22, 2005 large scale cell culture came of age with the success of highdose, chronically administered monoclonal antibodies mabs. The bioreactor controls temperature, agitation, ph and dissolved oxygen. Comprehensive study on wave bioreactor system to scale up the. Everything you ever wanted to know about cell culture. Multifors 2 parallel bioreactor system for smallscale.

Cell culture scaleup in stirredtank singleuse bioreactors. The data for a small scale bioreactor are a 100 litres fermenter with 187. A singleuse vessel option adds further flexibility. The labfors 5 cell is always application optimized for your cell culture bioprocess. Using doe with micro bioreactor improves process control for. These challenges are cell line and process specific. Table 1 lists common needs and expectations related to scale up of cell culture bioreactors that industryoriented bioengineers frequently mention. It will continue to grow if supplied with appropriate.

Scale up of bioreactor systems prathibha narayanan. Largescale cell culture came of age with the success of highdose, chronically administered monoclonal antibodies mabs. Other potential pitfalls include not accounting for changes in bioreactor performance as a function. This experiment demonstrates how a robotically controlled microbioreactor system can be combined with doe methods to optimize cellculture media and feeding. Mammalian cell culture bioprocesses are increasingly gaining importance in the biopharmaceutical industry.

Cellscales bioreactors provide insights into the response of cells and tissues to mechanical stimulation. Optimizing bioprocess scaleup from milligrams to kilograms. With multifors 2 you can work with up to six bioprocesses in parallel. Cellscale mechanoculture b1 biaxial stretching on a. Nov 21, 2019 mammalian cell culture bioprocesses are increasingly gaining importance in the biopharmaceutical industry. Doe helps optimize a cell culture bioproduction system. Cellscale also has extensive experience in developing custom solutions that exceed expectations. Scaleup analysis for a cho cell culture process in largescale. The small scale bioreactor is most similar to in situ conditions for cell growth because it can be monitored and optimized throughout a run.

Newly emerging technologies should enhance cell culture process development, scaleup, and process control significantly. 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. The m80 sm transmitter optimizes bioreactor system scalability by providing consistent inline measurement for all reactor sizes. Most often, initial experiments are performed using shake flasks but the conditions in the small scale bioreactor differ significantly from the shake flask. Advanced analytical capabilities including online glucose and lactate measurement, offgas measurement and viable biomass cell density measurement allow predictive process. The entire assembly can be sterilized and is suitable for longterm cell culture in a laboratory incubator. The main difference between these two lines is the aspect ratio of the bioreactors. He managed cell culture bioprocessing in both singleuse and conventional stirred tank bioreactors. Sartorius stedim biotech supplies the widest range of cell culture bioreactors for research and development work through to pilot and cgmp manufacture. Scaling up your cell cultures to bioreactors biocompare. The multifors 2 is a compact, freestanding device with up to six culture vessels on three base units. Bristolmyers squibb largescale cell culture biologics manufacturing facility project.

Tffuf is tangential flow filtrationultrafiltration. Cellscale mechanoculture t6 bioreactor for fibrelike. Perfusion, or upstream continuous bioprocessing, has been practiced in cell culture since the 1980s but with limited adoption. Optimization of lentiviral vector production for scaleup in. The system can also be adapted to wider sheetlike specimens and fiber specimens. Singleuse technology and support for solving your biomanufacturing challenges achieving the delicate balance of product quantity, quality. Typical applications range from small scale protein expression to media or process optimization studies. Parallel processing, precise control of all relevant parameters, userdefined profiles, and innumerable automation features result in accelerated and highly efficient process development. The thermo scientific hyperforma rocker bioreactor is controlled by the hyperforma g3lab controller and trubio software, providing a complete, readytouse solution.

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. This design is stated to create separate cell growth and aeration zones. Bioreactor scalability is critical to streamlining the adaptation of culture volumes during process development and manufacturing. In this webinar, we discuss several scaling approaches, such as constant tip speed, kla, and power numberbased scale up. Applications data support solutions to overcome your cell culture scale up challenges ge is dedicated to developing resources to help address. Mammalian cell culture bioprocesses are increasingly gaining. This bioreactor provid es a sufficient surface f or the large scale. 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.

Scaleup of cell clarification operations for much higher cell masses 30m. 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. 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. Bionet is the right partner to deliver the bioreactor you need for the successful industrial scale up of your cell culture or fermentation processes. Scale up of cell culture bioreactors is a challenging engineering work that requires wide competence in cell biology, mechanical engineering and bioprocess design. Xdr bioreactor systems offer the following benefits. 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. A number of benchtop mini or microbioreactors are available that incorporate sensors and use software to optimize conditions. Table 1 lists common needs and expectations related to scaleup of cell culture bioreactors that industryoriented bioengineers frequently mention. 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. The choice of bioreactor for cell culture is often decided based on.

In this webinar, we discuss several scaling approaches, such as constant tip speed, kla, and power numberbased scaleup. Xcellerex xdr singleuse bioreactor systems provide scalable and robust stirredtank performance for up to 2000 l in both cgmp and noncgmp environments. 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. Cell culture process performance at 2 l, 10 l and 80 l scale. For overcoming the above difficulty and to facilitate scale up of plant cell culture bioreactor a design of low shear bioreactor has been reported.

Dasgip parallel bioreactor systems bioprocess systems. Once these are applied in combination with highperforming, singleuse bioreactors, then extremely high cell densities will become a reality. In this article, a new approach for cell culture bioreactor scale up is suggested that is b ased on biomechatronic design methodology. 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. 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. The singleuse system can be exchanged with a glass multiuse system whenever your process or workflow needs a different approach. Comprehensive study on wave bioreactor system to scale up. Xcellerex xdr 50 to 2000 singleuse stirredtank bioreactors.

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. Fundamentals of bioreactor design are the following functions. In continuous bioprocessing, pilot scaleup is a key transitional step. Applikon offers tailormade and fully reproducible solutions with 500 ml and 3 l singleuse bioreactors.

Typical applications range from smallscale protein expression to media or process optimization studies. Scaleup of cell culture bioreactors using biomechatronic design. 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. Its size and the ability to preprogram the bioreactor conditions results in a costeffective solution to our bioreactor needs. The thermo scientific hyperforma singleuse bioreactor s. Everything you ever wanted to know about cell culture process. We have systems optimized for highthroughput, realtime imaging, 3d scaffold use, and multimodal stimulation. Using doe with micro bioreactor improves process control. Unique biaxial agitation improves cell culture performance. Typically, benchtop bioreactors are operated in the performance design space of larger bioreactors to model scale up performance, according to parrish m.