Scaledown model closely predicted scaleup performance. The fundamental challenges of such processes are related to the high viscosity and inhibitor contents of the medium. Sep 30, 2014 yeast scaleup example production goal. Aerobic fermentative bioprocessing using filamentous microorganisms cover a wide range of industrially important bioproduct formation systems. The recovery of the product is also a difficult job and needs lots of efforts to arrive at the right process conditions. Failing to use representative feedstock during scaleup testing can set you up for big problems later. Moreover, modern methods of genetechnology makes it possible for the. Scale up studies scale up studies are studies carried out at the laboratory or even pilot plant scale fermenters to yield data that could be used to extrapolate and build the large scale. Jul 03, 2017 scale up studies scale up studies are studies carried out at the laboratory or even pilot plant scale fermenters to yield data that could be used to extrapolate and build the large scale industrial fermenters.
Shortcomings of available methods and potential routes to better ones are discussed in this article. Variables to be considered when changing fermentation scale implementing a scaling activity summary references and f. In a physiological sense, fermentation refers to a process that produces energy by breaking down of energyrich compounds under anaerobic conditions. A unique requirement for commercial biopharmaceutical process scale up is process validation. Scaleup approach for fermentation process of production of. Scale up means increasing the scale of a fermentation, for example from the laboratory scale to the pilot plant scale or from the pilot plant scale to the production scale. Then, when the scale is increased, the broth will become more and more heterogeneous. Upstream processing includes formulation of the fermentation medium, sterilisation of air, fermentation medium and the fermenter, inoculum preparation and inoculation of the medium. Effective scale up is essential for successful bioprocessing. The optimization of the fermentation process is included in the strategic analysis of the viability of a project. Scale up approach for fermentation process of production of bacillus thuringiensis var kenyae based biopesticide r g muley, s sarkar, b l bhan, arunkumar,m narayanan and s r aik rescarch and development, hinuustan antibi otics limited, pi mpri. High content of waterinsoluble solids wis is required for simultaneous saccharification and co fermentation sscf operations to reach the high ethanol concentrations that meet the technoeconomic requirements of industrial scale production. Jan 03, 2008 introduction to scale down and scale up in fermentation technology two of the most common phrases one often met in fermentation technology research is scaling up and scaling down studies. Scaleup of escherichia coli fermentation from small scale.
Jun 01, 2018 scaleup of industrial microbial processes article pdf available in fems microbiology letters 365 june 2018 with 1,3 reads how we measure reads. Fermentation, scale up, pilot plant scale, scale down i. Scaleup approach for fermentation process of production of bacillus thuringiensis var kenyae based biopesticide r g muley, s sarkar, b l bhan, arunkumar,m narayanan and s r aik rescarch and development, hinuustan antibi otics limited, pi mpri. Optimizing scaleup fermentation processes michel thiry and doriano cingolani there are many aims associated with the optimization of fermentation processes. Lab performance plant performance plant target scale down protocol. Often, the commercial business model will be to produce syngas by gasification of biomass or msw, yet the lab or pilot will operate on syngas generated. Growth of anaerobic processes historically scale up of aerobic processes fuel to food processes ici, ltd. Scale up would be very simple if all parameters affecting bacteria remained the same. Scale up projects often require implementation of new equipment or modification of existing equipment. This chapter describes relevant aspects of industrialscale fermentation, an expanding area. Existing fermentation scaleup methods cannot meet adequately the technical and economic demands of the modern biotechnology industry. Scale up studies are executed at the laboratory or. Production processes for monoclonal antibodies intechopen. The fermentation was first carried out at laboratory scale, in 2 l bioreactor, than at semipilot scale, in 20 l bioreactor.
This chapter covers a broad scope of issues related to microbial fermentation process scale up and describes specific steps to plan and execute a scale up project. Effect of culture media and scaleup on lactic acid and biomass productivity. Fmea, 6sigma approaches fermentation facility definition. Lab to industrial plant implementation january 28, 20 prepared for. Scalingup of highcelldensity fermentation hcdf of pichia pastoris from the lab or pilot scale to the demonstration scale possesses great significance because the latter is the final.
The scale up process is very challenging as the conditions followed during shake flask or lab fermentation may not suit for high volume cultivation. Scaling up industrial microbial processes for commercial production is a. Operational practices such as batch, fed batch, and continuous culture are described. We try to build industrial size fermenters capable or close of producing the fermentation products as efficient as produced in small. Optimization is expected to increase the yield of the final product but. Scaling up industrial microbial processes for commercial production is a highstakes endeavor, requiring time and investment often exceeding that for laboratory microbe and process development. However, the phrase scaling up is more commonly understood and practiced during the designing of industrial scale fermentors. Scaleup would be very simple if all parameters affecting bacteria remained the same. Antibodies are glycoprotein structures with immune activity. In scaling up a conventional stirred tank fermentor stf the designer must provide for at least, and at the lowest possible cost. The first monoclonal antibodies mabs have emerged from a survey of hybridomas, and. This scaleup procedure has been applied 11 to the data of rogovin et al. This is the basis of food fermentation, which is commonly used in the food industry in order to produce diverse food products and also as a food preservation.
Best practices for successful scale up of industrial. The seed train for the fermentation required preparation of a preculture grown in shake flasks. Scale up of aerobic fermentations is often carried out on the basis of a constant oxygen transfer coefficient. Optimization and scale up of industrial fermentation.
Increase in scale means an increase in volume and the problems of process scaleup are due to the different ways in which process parameters are affected by the size of the. Any industrial fermentation operation can be broken down into t hree main stages, viz, upstream processing, the fermentation process and downstream processing. However, as fermentation facilities usually are not strictly designed according to scaleup criteria and the process conditions in the culture vessels thus may differ significantly and since any strategy and model can only insufficiently consider and reflect the highly complex interdependence and mutual interaction of fermentation parameters. Increase in scale means an increase in volume and the problems of process scale up are due to the different ways in which process parameters are affected by the size of the. A time course of a typical daunorubicin scale up fermenter 10, 0001 run is shown in fig. Ppt pilot plant scale up technique powerpoint presentation. Scaleup approach for fermentation process of production. The relative sizes of the scaling groups for this plant are shown in table r7. Optimization and scale up of industrial fermentation processes. To increase product yields and to ensure consistent product quality, key issues of industrial fermentations, process optimization and scale up.
Mixing time t mix, defined as the period of time required for the homogeneous distribution of a small volume of pulsating material in the bulk of the liquid, was used for scale up to adjust proper mixing conditions in large vessels. The same issues arise when doing fermentation with syngas or digester gas as a feedstock. The results indicated that harvest litres in the scale up fermenter have increased from run to run. Pdf optimizing scaleup fermentation processes sujitha. Comparing the scaleup of anaerobic and aerobic processes. While it is desirable to keep as many operating parameters constant as possible during the scaleup, the number of constant parameters realizable is limited by the degrees of freedom in designing the largescale operation. Challenges in fermentation scale up process for production of. Scaleup of aerobic fermentations is often carried out on the basis of a constant oxygen transfer coefficient. Of operations cell and cell products fermentation facility waksman. Organism response under scale down protocol identical to large scale conditions.
Optimizing scaleup fermentation processes sciencedirect. The traditional seed train includes thawing a vial and inoculating into shaker flasks for a certain number of stages. Even though the number of publications on this topic in the field of gas fermentation is limited, many of the approaches developed through the metabolic engineering of e. Scale up to 200 l fermentations after integrating all the information gathered from the earlier experiments, the engineers devised a 200 l fermentation protocol for use in a new brunswick bioflo pro with 240 l vessel 75. 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.
Variables to be considered when changing fermentation scale implementing a scaling activity summary references and. Scale up and scale down of fermentation processes practical. In large fermentors, oxygen can be depleted in some area of the reactor 19. Scaleup of escherichia coli fermentation from small. The quality of the communication between the developers of the fermentation and the dsp is pivotal to the success of the scaling up the process. To increase product yields and to ensure consistent product quality, key issues of industrial fermentations, process optimization and scale up are aimed at maintaining optimum and homogenous reaction conditions minimizing microbial stress exposure and enhancing metabolic accuracy. Submerged fermentation the microorganisms and the substrate are present in the submerged state in the liquid medium. The purpose of a seed train is to propagate cells to a desired mass for inoculation into the production bioreactor. Large scale fermentation manufacturing services for the. Improved scaleup strategies of bioreactors springerlink.
Optimzing scaleup fermentation processes request pdf. Presented at the annual meeting of the american institute of chemical engineers, salt lake city, utah, november 8, 2007. Scaleup of industrial microbial processes article pdf available in fems microbiology letters 365 june 2018 with 1,3 reads how we measure reads. Immunoglobulins are produced and secreted by b lymphocytes in response to the presence of antigens. However, in an industrial scale a particular defined starter culture, which has been developed under controlled conditions, is of first preference so that the qualities of the finished product could be consistently maintained day after day. Lab performance plant performance plant target scaledown protocol. The fermentation must thus be developed concomitantly with the purification because they will affect each other. For each individual product, process and facility, suitable strategies have to be elaborated by a comprehensive. Scaleup chemical engineering in chemical engineering, the migration of a process from the labscale to the pilot plantscale or commercial scale. Proof of concept and feasibility study for large scale production l. Optimization is expected to increase the yield of the final product but the process must be compliant with good manufacturing practices,the. However, limitation of using t mix as scale up criteria is that it increases markedly with the. Existing fermentation scale up methods cannot meet adequately the technical and economic demands of the modern biotechnology industry. To do so, we first investigated engineering parameters critical for scaling up fermentation processes, such as vessel and impeller geometry, oxygen transfer rate.
Scaleup, a type classroom layout and learning environment. However, as fermentation facilities usually are not strictly designed according to scale up criteria and the process conditions in the culture vessels thus may differ significantly and since any strategy and model can only insufficiently consider and reflect the highly complex interdependence and mutual interaction of fermentation parameters. Production of polyhydroxybutyrate from lignocellulosic. Those who take a systematic approach will be rewarded with a consistent largescale fermentation that meets performance expectations and enables good downstream performance as well. This was due to the fermentation improvement program including scale up strategy.
Large solvent the heat and mass transfer are more efficient amenable for modeling the process process scaleup is easy. The scaleup of microbial batch and fedbatch fermentation processes. In scale up of bioreactors mixing time is often used as criteria. This scale up procedure has been applied 11 to the data of rogovin et al. High content of waterinsoluble solids wis is required for simultaneous saccharification and cofermentation sscf operations to reach the high ethanol concentrations that meet the technoeconomic requirements of industrialscale production. Approached properly, scale up can be executed successfully. In order to scale up production, pathway gene expression needs to be optimized to minimize metabolic bottlenecks and unwanted side products 109111. Jan 21, 2016 scaling up of highcelldensity fermentation hcdf of pichia pastoris from the lab or pilot scale to the demonstration scale possesses great significance because the latter is the final. They are able to identify or induce a neutralizing immune response when they identify foreign bodies such as bacteria, viruses, or tumor cells. The two principal fermentation schemes submerged culture and solidstate cultivation are discussed. Due to the larger size and scale of industrial fermentation setups it is vital to succeed beforehand studies of possible complications, due to increase in scale, and to sort out ways to tackle them.
With the tremendous diversity of organisms and products in industrial fermentation, a precise and onesizefitsall strategy for scale up is not. Recognition of and attention to scaledependent fermentation parameters is fundamental to reducingeven eliminatingfermentation as a scaleup risk. This process is the important step for transferring benchtop fermentations to mass production. Scaleup of escherichia coli fermentation from small scale to. Effective scaleup is essential for successful bioprocessing. Challenges in fermentation scale up process for production. Request pdf optimzing scaleup fermentation processes there are many aims associated with the optimization of fermentation processes. Scale up of fermentation process pdf publication a novel approach for scalingup a fermentation system. Reference number6 various differing types of models exist, each suited to different situations in scaleup fundamental modelsany model based on a theoretical understanding of the process mechanismsused to describe the system from first principles of thermodynamics, phase equilibrium, and kineticsresidence time distribution models are used to treat continuous, steady state. Bioreactor scaleup and kinetic modeling of lactic acid. While it is desirable to keep as many operating parameters constant as possible during the scale up, the number of constant parameters realizable is limited by the degrees of freedom in designing the large scale operation. Omissions, oversights and errors can be costly, even fatal to the program. It is important to understand that the process of scalingup a fermentation system is frequently governed by a number of important engineering.
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