The essence of scale up of a fermentation process is to demonstrate fermentation production at large scale resulting in the same productivity and quality as that developed at small scale. The 50l and 250l subs were used for scale up and pilot runs with the optimized process a 14day fedbatch culture. Scaleup of cell culture bioreactors using biomechatronic. A section of the chapter discusses specifically the scale up of the bioreactor operational parameters such as agitation, airflow rate, and cooling capability. Request pdf bioreactor design and scaleup design and selection of cell culture bioreactors are affected by cellspecific demands, engineering aspects, as well as economic and regulatory. Stamper and cillian mccabe, bioprocess research and development, eli lilly and company bioreactor design. Cooling can be provided by either making the draught. Scaleup and comparison studies evaluating disposable. For each reactor configuration,the appropriate process conditions depend on parameters such as the reactor scale,particle size distribution,slurry density,slurry viscosity,oxygen demand of the biomass, and the solids holdup kleijntjens, 1991. A bioreactor is divided in a working volume and a headspace volume. A practical approach in bioreactor scaleup and process. Engineering characterisation of a rocked bag bioreactor. A summary of various strategies for bioreactor scaleup is given below. The pall icellis is a compact fixedbed bioreactor with an integrated perfusion system.
The traditional seed train includes thawing a vial and inoculating into shaker flasks for a certain number of stages. A new orbitalmixed 3l12l singleuse bioreactor for cell culture scaleup and bulk protein production smallbatch therapeutic protein production requires predictable scaleup to meet bulk delivery timelines. Just fill out the form below to read the full ebook of this special report. This study is conducted to evaluate the effect of scaleup on growth and lactic acid production by enterococcus faecalis slt. This work studies the scalability between 3 different volumes of lab scale bioreactors, 500 ml, 3 l and 15 l. Request pdf scale up and scale down methodologies for bioreactors scale up is usually complicated by the fact that bioprocesses in general are gasliquid systems, whereby the liquid phase. Scale up is perhaps one of the hardest and most complex steps of any fermentation process for engineers. A novel method for the scaleup culture of chinese hamster ovary cho cells in a packedbed bioreactor is developed wherein microcarriers, attached with cho cells in a microcarrier culture system. As companies scale up to pilotproduction bioreactors, they need to. Geometrical similarity h l1 d t1 h l2 d t2 h l3 d t3 scaleup of bioreactor by chew few ne. A new orbitalmixed 3l12l singleuse bioreactor for cell. Testing and simulation approaches for singleuse bioreactor. Design of experiments with smallscale bioreactor systems.
Impeller tip speed vtip or gassed power input of the stirrer per volume of liquid in the bioreactor pgvl are used to. Design, characterization, and scaleup strategy for a new. Scaling up your cell cultures to bioreactors biocompare. Application note 306 scaleup of escherichia coli fermentation from small scale to pilot scale using eppendorf fermentation systems download. With the scale up criterion such as similar power input per volume or o2 volumetric mass transfer coefficient kla, adequate oxygen supply and cell growth can be largely achieved. Pdf bioreactor scaleup and oxygen transfer rate in. The fermenter or bioreactor are the core of this scale up project. Effect of culture media and scaleup on lactic acid and biomass productivity. Scaleup of bioreactor systems study of problems associated with the transfer of experimental data from.
For this reason the oxygen transfer rate condition has been often chosen as the main criterion for scaling up. Successful scale up requires careful calculation of the geometric relations of the large scale bioreactor to avoid heterogeneities. Improved scaleup strategies of bioreactors springerlink. Introduction scientific background workflow poster downloads. Bioreactor scaleup and oxygen transfer rate in microbial processes. Scale up is the process of expanding a fermentation process from a smaller scale fermenter, where operational and production parameters have been studied, to a larger scale. Most fullscale fermenters have a pv level of about wl, while many pilot fermenters have a pv in the range of 510 wl. Author links open overlay panel felix garciaochoa emilio gomez.
In general, scaleup of a microbial process comprises the transfer of a new or an improved. Scaleup of cell culture bioreactors using biomechatronic design. Bioreactor scale up and oxygen transfer rate in microbial processes. Scaleup and scaledown strategies are a key for successful implementation of. The 50l and 250l subs were used for scaleup and pilot runs with the optimized process a 14day fedbatch culture. The bioreactor system comprises tray for positioning of a cell culture bag having adjustable volume, a. The ideal scaleup criterion is that parameter which has the same numerical value as the volumes of the geometrically similar bioreactors increase in size. Regardless what kind of production process a bioreactor or.
Engineering characterisation of a rocked bag bioreactor for. Optimization of lentiviral vector production for scaleup in. The emergence of a variety of geometrically dissimilar singleuse bioreactor platforms provides users with both challenges and opportunities as they look to incorporate this technology across the range. Scale up and scale down strategies are a key for successful implementation of. The present invention relates to a novel bioreactor system for cell cultivation. Scaleup is the process of expanding a fermentation process from a smallerscale fermenter, where operational and production parameters have been studied, to a larger scale.
The fermentation was first carried out at laboratory scale, in 2 l bioreactor, than at semipilot scale, in 20 l bioreactor. If you choose to scale up to larger bioreactors, you will be one step ahead after optimizing conditions for your smallscale bioreactor. Observations on scaleup yusuf chisti department of chemical engineering, university of waterloo, waterloo, ontario, canada n2l 3gl received 26 october 1992. Table 1 lists common needs and expectations related to scale up of cell culture. Scale up to 1,000l perfusion in a disposable stirred tank bioreactor. Engineers must take into account all aspects that affect the. Scale up to bench bioreactor culture from shaker flasks presented several challenges. Calculate the agitator speed to give the same pv as.
If what you need is a fully customized bioreactor, beyond the standard features, or bigger volumes than. Jul 14, 2014 if you choose to scale up to larger bioreactors, you will be one step ahead after optimizing conditions for your smallscale bioreactor. Bioreactor parameter optimization was conducted to attain equivalence between the two culture scales in. Best practices from scaleup to control in biomanufacturing, knowledge of scaleup, processing and control should be shared and documented in order to achieve and sustain operational excellence. The stirred tank bioreactor str typically, the working volume will be 7080% of the total fermenter volume. Use bioreactors by emily stoker, master of science utah state university, 2011 major professor. Bioreactor scaleup and oxygen transfer rate in microbial. 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 in bioreactor free download as powerpoint presentation.
Scaling up is a determinant step during process development. Scribd is the worlds largest social reading and publishing site. With the scaleup criterion such as similar power input per volume or o2 volumetric mass transfer coefficient kla, adequate oxygen supply and cell growth can be largely achieved. A rocked bag bioreactor has been fully evaluated at 10 to 50 l scale. Ppt bioreactor systems powerpoint presentation free to. The working volume is the fraction of the total volume taken up by the medium, microbes, and gas bubbles. Bioreactor design 145 up through the draught tube to the head space of the bioreactor, where the excess air and the byproduct, co 2, disengage.
Overcoming scaleup challenges during culture media. Scale up and oxygen transfer rate in aerobic bioprocesses. Oct 16, 2016 scale up of bioprocess pdf interactions between physicochemical and biological parameters. Scale up of bioprocess pdf interactions between physicochemical and biological parameters. As another example, a multipronged approach can also be used to i demonstrate equivalent performance between traditional alloy and proposed singleuse equipment, ii validate cfd simulation, and iii extend performance projections to intermediate and full scale equipment. However, co 2 stripping in the growth phase is often inadequate. Here, an orbitalshaken 3l12l bioreactor is presented as an alternative to stirred vessels for batch production and scale up. This chapter covers a broad scope of issues related to microbial fermentation process scaleup and describes specific steps to plan and execute a scaleup project. Bioreactor scaleup is a critical step in the production of therapeutic proteins such as monoclonal antibodies mabs. Data on cell density, fractional viability, and protein concentration were collected and compared across the scales and types of reactors.
Efficient scaleup of bioreactors for production of mammalian cells is a great challenge in bioengineering. T1 scaleupbioreactor design and culture optimization. It differs from the stirred tank in that mixing occurs due a rocking motion to generate waves to prevent cell settling and provide oxygenation. When leaving the lab and designing your industrial solutions numerous challenges have to be solved. Scaleup is perhaps one of the hardest and most complex steps of any fermentation process for engineers. Developing biopharmaceuticals or biological cell materials at small. Here, common approaches and challenges in industrial mammalian cell culture scale. The scaleup studies based on the constant oxygen transfer coefficient, kla from 16 l to. Beginning with harvest of material from a bioreactor, downstream processing removes or reduces contaminants to acceptable levels through several steps that typically include centrifugation, filtration, andor chromatographic technologies. Cell culture bioprocess and bioreactor engineering organizers. Sep 30, 2014 yeast scaleup example production goal. Bioreactor engineering chapter 10 scaleup of bioreactor. Here, an orbitalshaken 3l12l bioreactor is presented as an alternative to stirred vessels for batch production and scaleup. Overcoming scaleup challenges during culture media development.
The attributes of a bioreactor should comply with design requirements such as sterilization, simple construction and measuring, process control devices, regulating techniques, scaleup, exibility in operations, compatibility with upstream and downstream processes, antifoaming measures etc. Scalability in laboratory bioreactors based on constant. Us20180002655a1 bioreactor system for cell cultivation. Each method provides challenges for scale up, but has found a place in production. Scaleup criteria of bioreactor article pdf available in kemija u industrijijournal of chemists and chemical engineers 531. The oxygen transfer rate otr must be known, and if possible predicted to achieve an optimum design operation and scaleup of bioreactors. Now an approximate full scale pv and u s are known.
Initial k l a was identified to be a key factor affecting cell growth and production of ginseng saponin and polysaccharide by high. Zoro sees smallscale bioreactor results as a tool which is highly predictive of results in larger bioreactors. Each method provides challenges for scaleup, but has found a place in production. The attributes of a bioreactor should comply with design requirements such as sterilization, simple construction and measuring, process control devices, regulating techniques, scale up, exibility in operations, compatibility with upstream and downstream processes, antifoaming measures etc. Bioreactor scaleup and kinetic modeling of lactic acid.
Some scientists and engineers in biotech industry dedicate their entire careers scaling up various bioreactor processes, and each time they may encounter something new. Scalingup is a determinant step during process development. 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. Scaleup and scaledown methodologies for bioreactors. Biological engineering this study was performed to increase knowledge of oxygen mass transfer k. Successful scaleup requires careful calculation of the geometric relations of the largescale bioreactor to avoid heterogeneities. The biostat bdcu ii benchtop bioreactor sartorius stedim biotech is specifically designed for laboratoryscale parallel operations of up to six multiuse or singleuse culture vessels with one control tower. Scaleup bioprocess development for production of the antibiotic. More specifically, the invention relates to a compact bioreactor system which has several integrated functions and enables small scale static culture as well as scaleup rocking culture in the same bioreactor. Scaleup has been one of the major problems in bioprocess technology. Design a series of pilot runs using shaft speeds and airflow rates to bracket the values of pv and u s calculated for the full scale design of step 2. Up scalingup is a determinant step during process development. Wed like to understand how you use our websites in order to improve them.
Working initially with a smallscale bioreactor can enable highthroughput early studies. Request pdf bioreactor design and scale up design and selection of cell culture bioreactors are affected by cellspecific demands, engineering aspects, as well as economic and regulatory. Under typical operating conditions, singleuse rocked bag bioreactor tm were found to vary from 771 s, klao2 from 3. Design, characterization, and scaleup strategy for a new singleuse productionscale bioreactor gennews. Scaleup considerations for monoclonal antibody production. Chapter 4 oxygen transfer in a production scale bioreactor. T1 scale up bioreactor design and culture optimization. Calculate the pilot airflow based on using the same u s as full scale. As already indicated, the oxygen transfer rate can control the overall rate of the bioprocess, and as a consequence, it can determine the capacity of a bioreactor. Table 1 lists common needs and expectations related to scaleup of cell culture. Scaleup to bench bioreactor culture from shaker flasks presented several challenges. In this article, the work done by various engineers in bioreactor design and prediction of possible environmental gradients in bioreactors is presented and discussed, with emphasis on reactors for cell culture.
A new orbitalmixed 3l12l singleuse bioreactor for cell culture scale up and bulk protein production smallbatch therapeutic protein production requires predictable scale up to meet bulk delivery timelines. Bioreactor scale up is a critical step in the production of therapeutic proteins such as monoclonal antibodies mabs. Cell culture scaleup in stirredtank singleuse bioreactors. A slurry bioreactor can only work properly if these three measures are balanced. Pdf in the scaleup of bioreactors one of the most commonly used criteria for aerobic. The single use rocking platform bioreactor is similar to the stirred tank, and provides a regulated environment. The purpose of a seed train is to propagate cells to a desired mass for inoculation into the production bioreactor.
The degassed liquid then flows down the annular space outside the draft to the bottom of the bioreactor. N2 tubular and the flat plate are the two most common general designs of microalgal photobioreactors. Oct 27, 2017 design, characterization, and scaleup strategy for a new singleuse productionscale bioreactor gennews. Pdf scaleup strategy for bioreactors with newtonian and non. Development of an industrial biotechnology process using. Process scaleup between 3 different stirred tank bioreactors was studied.
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