Dynamic similarity requires both geometric and kinematic similarity and adds the characteristic. Bhangale and yan chen and anurag khetan and jim furey, year2018. Cell culture scaleup in bioblu c rigidwall, single use. Transfer of technology and its scale up by 150fold was completed within a. In scale up of bioreactors mixing time is often used as criteria. This table is not designed to represent a specific set of experimental data. Bioprocess development an overview sciencedirect topics. For each particular process, an adequate and comprehensive approach has to be established, which includes pinpointing key issues required to ensure proper scale. Scaleup definition act of using results obtained from laboratory studies for designing a prototype and a pilot plant process.
Scaleup and scaledown strategies are a key for successful implementation of. How to successfully scaleup automated singleuse bioprocesses. This step is notorious for performance losses and delays in. Hence, for a biosimilar processes, you might loose your product bioequivalence during scale up.
Succeed at bioprocess scaleup while fermentationbased syntheses were once reserved for producing highvalue specialty chemicals and biopharmaceuticals, bioprocess routes now are gaining increasing attention for commodity products. 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. Additionally, the microcarriers are surfacetreated to enhance cell attachment, maximizing cell yield and viability. Features consistency usp class vi polystyrene material provides a consistent. In addition to an overview of the theory of multiscale analysis for fermentation process, examples of scaleup practice combining microbial physiological parameters with bioreactor fluid dynamics are also described. The primary scope of this project was to investigate the scaleup capabilities of eppendorf bioblu singleuse vessels for cell culture applications from small to pilot scale. 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. However, limitation of using t mix as scale up criteria is that it increases markedly with the. Corning microcarriers for bioprocess scaleup advanced. Biologics manufacturing considerations for scaleup. Nonetheless, the design, development and implementation of bioprocesses can present variations depending on intrinsic characteristics of the overall process.
Catherine shaffer holds a masters degree in biological chemistry and has worked as a research scientist. However, loss of production performance upon scalingup, including reduced titer, yield, or productivity, has often been observed, hindering the commercialization of biotech innovations. Keywords bioprocess engineering 4 scaleup 4 bioprocess monitoring 4. Commit your blunders on a small scale and make your profits on a large scale. In addition to an overview of the theory of multi scale analysis for fermentation process, examples of scale up practice combining microbial physiological parameters with bioreactor fluid dynamics are also described. Recent developments in scale down studies assisted by computa. Bioprocess scaleupdown as integrative enabling technology. For the scale up of a batch bioprocess the effect of the feeding components base for neutralisation of product, oxygen on the fermentation show the most important influence. Typically, the first significant bioprocess scale up goes handinhand with the technology transfer of the process into gmp biologics manufacturing. Yes, it is unavoidable that your manufacturing process will undergo a scaleup at least once in the life cycle of your product. Keywords bioprocess engineering 4 scale up 4 bioprocess monitoring 4. For the scaleup of a batch bioprocess the effect of the feeding components base for neutralisation of product, oxygen on the fermentation show the most important influence. You develop, optimize and characterize bioprocesses in laboratory scale.
Scaleup bioprocess development for valinomycin production in e. Optimizing bioprocess scaleup from milligrams to kilograms. A new ema paper on comparability testing now provides new insights on scientific best practices. Bioprocesses development is generally initiated on the laboratory scale and progressively scaled up to larger volumes at the pilot plant level, and finally, production scale. Comments for how to successfully scaleup automated singleuse bioprocesses. Your drug product quality attributes might change during scale up.
The ultimate goal for process development is, however, the realization of largescale commercial production. Bioprocessing technology transfer and scaleup bioprocesing. Mar 23, 2015 comments for how to successfully scale up automated singleuse bioprocesses. Process development pilot scale production bench scale experiments bioblu 0. Developing the bioprocess scale down model is the core of. Jun 29, 2017 optimizing bioprocess scale up from milligrams to kilograms. Cell culture scaleup in stirredtank singleuse bioreactors.
Scaling up normalflow microfiltration processes bioprocess. Over the last few years, the bioprocessing industry has had a high throughput rate for new product candidates in its attempt to find the next pharmaceutical blockbusters. Bioprocess scale up is a critical step in process development. Jun, 2011 the ultimate goal for process development is, however, the realization of largescale commercial production. Corning microcarriers are designed to simplify your scaleup processes. Certainly, you would like to follow the advice given by h. Several questions are currently adressed in research. Bioprocess development and scale up science exchange lets you compare quotes from over 20 leading service providers.
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. Scaleup bioprocess development for production of the. As you scale up, you want to prevent concentration gradients and achieve homogeneity throughout each vessel. The major advance in bioprocess development which occurred during world war 2 was the large scale production and purification of penicillin, 8 using the penicillium mould discovered nearly 20 years earlier. Request pdf bioprocess scaleup technically applying biological knowledge from a benchscale bioreactor to a fullscale bioreactor is not simple job. Yet, you expect that the insights from laboratory scale do not change during scaleup. The challenge of bioprocess scaleup it is different this is not discovery research this is not applied research this is not single unit operation development it requires a different set of expertise engineering process mechanical automation mechanical aptitude it is expensive so is failure it is larger scale dont ignore standard scaling rules to the small. Bioprocess development upstream and downstream technologies. Recent developments in scaledown studies assisted by computational fluid dynamics cfd and powerful stimulusresponse metabolic models afford. Journal of chemical technology and biotechnology 2010.
Pdf this chapter addresses the update progress in bioprocess engineering. The microcarriers are sterile, readytouse, and available in closed systems packaging to be used directly. Xia j, wang g, lin j, wang y, chu j, zhuang y and zhang s. Yes, it is unavoidable that your manufacturing process will undergo a scale up at least once in the life cycle of your product. Scaleup can be particularly challenging for biologics as there are many variables at. Bioflo 320 bioprocess control station with bioblu 50c singleuse vessels.
Key factors for bioprocess technology selection, scale up and engineering of new facilities biocatalyst raw materials process technologies products scale economics s cale e conomics b. However, loss of production performance upon scaling up, including reduced titer, yield, or productivity, has often been observed, hindering the commercialization of biotech innovations. The microcarriers are sterile, readytouse, and available in closed systems packaging to be used directly with bioreactors. This had led to an acceleration in pharmaceutical outsourcing for process and. Corning microcarriers for bioprocess scaleup corning microcarriers are designed to simplify your scaleup processes. This is the main purpose obvious we doing the scale up as for example, oxygen transfer is of the rate limiting step in the aerobic bioprocess due to low solubility. In addition to an overview of the theory of multiscale analysis for. However, there still exists a gap between the theory and. The ultimate goal for process development is, however, the realization of a largescale production. The ultimate goal for process development is, however, the realization of a large scale production. Nov 23, 2017 for bioprocess development and manufacturing, the question how to demonstrate a successful bioprocess scale up is a highly debated topic. Bioprocess scaleup is a critical step in process development. Adding to the pressure on bioprocess development teams is the need to rapidly reach a stage at which sufficient quantities of representative material can be manufactured and used in support of various preclinical and clinical evaluations.
The impact of gradients on the cellular behavior, regulatory network and population homogeneity are observed. Corning microcarriers are designed to simplify your scale up processes. May 29, 2017 this then is a good opportunity for presenting a modernized version of the scale. This will be shown in this presentation in the case of different mixing conditions as a function of scaleup. Advances and practices of bioprocess scaleup for example, with increasing liquid height, hydrostatic pressure at bottom of the large reactor can easily reach over 1 bar, which in turn results in. Scale up of bioprocess pdf interactions between physicochemical and biological parameters. Cell cultivation process transfer and scaleup bioprocess. Professor of bioprocess engineering and head of school of biotechnology, dublin city university, glasnevin, dublin 9, ireland email. Jul 05, 2017 your bioprocess in manufacturing scale runs will run at suboptimal conditions. For the scaleup of a batch bioprocess the effect of the feeding. Instead, it is calculated based on average airwater correlations, and is intended to show how the pv and u s will tend to vary upon scaleup if effort is not made to. 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.
The traditional seed train includes thawing a vial and inoculating into shaker flasks for a certain number of stages. Of these most emphasis has been given to specific power input, oxygen transfer and impeller tip speed. Developing a computational framework to advance bioprocess. This will be shown in this presentation in the case of different mixing conditions as a function of scale up. To ensure that, you need a robust and predictive bioprocess scale down model. Furthermore, the methodology for process optimization and bioreactor scaleup. Bioprocess development and scaleup science exchange lets you compare quotes from over 20 leading service providers. Bioprocess scaleup howbeer muhamadali, ayun xu, david i. Hence, your laboratory results are representative and predictive for the final manufacturing scale. Aug 16, 2010 nonetheless, the design, development and implementation of bioprocesses can present variations depending on intrinsic characteristics of the overall process. This step is notorious for performance losses and delays in development.
Adding to the pressure on bioprocess development teams is the need to rapidly reach a stage at which. Bioprocess scaleup using a structured mixing model sciencedirect. Transfer of technology and its scaleup by 150fold was completed within a. Bioprocess development and scaleup science exchange. Scaling up biological processes from laboratory bench to process scale is complex and requires considering a number of factors to ensure process robustness.
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. Aug 28, 2006 succeed at bioprocess scale up while fermentationbased syntheses were once reserved for producing highvalue specialty chemicals and biopharmaceuticals, bioprocess routes now are gaining increasing attention for commodity products. Please note that, in an effort to combat spam, comments with hyperlinks will not be published. 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. Due to variability among raw materials and processes, most process developers use generous safety factors to ensure that their systems are not undersized. In microbial bioprocessing scale up although many criteria have been provided but among them only four criteria as given in table 8.
All projects aim to discover targets for strain and process optimization and suitable process analytical tools to improve scale up and industrial scale processes performance. Bioprocess scaleup using a structured mixing model. This had led to an acceleration in pharmaceutical outsourcing for process and analytical activities. For bioprocess development and manufacturing, the question how to demonstrate a successful bioprocess scale up is a highly debated topic. The rungekuttafeldberd method is used to solve the resulting integrated mathematical model. Advances and practices of bioprocess scale up for example, with increasing liquid height, hydrostatic pressure at bottom of the large reactor can easily reach over 1 bar, which in turn results in. Typically, the first significant bioprocess scaleup goes handinhand with the technology transfer of the process into gmp biologics manufacturing. The bioprocess industry is expected to increasingly deliver.
Three bioreactor sizes were selected to represent approximately 10fold scaleup between steps. 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. Key factors for bioprocess technology selection, scaleup and engineering of new facilities biocatalyst raw materials process technologies products scale economics s cale e conomics b. Methodologies for scaledown of microbial bioprocesses longdom. Pdf a uf df screening system for bioprocess development. Cell culture bioprocess and bioreactor engineering organizers. 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. Scale up 100 litre process kinetics productivity etc. Scaleup 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. Additionally, the microcarriers are surface treated to enhance cell attach. Metabolic profiling of geobacter sulfurreducens during. The microcarriers are sterile, readytouse, and available in closed systems packaging to be used directly with.
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