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Bioreactors

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Dieter Eibl – One of the best experts on this subject based on the ideXlab platform.

  • Encyclopedia of Industrial Biotechnology – Antibody Manufacture, Disposable Systems
    Encyclopedia of Industrial Biotechnology, 2010
    Co-Authors: Regine Eibl, Dieter Eibl

    Abstract:

    The growing demand for biotherapeutics and, in particular, antibodies has resulted in an increasing use of disposables over the last ten years. This concerns both, process development and commercial manufacturing, where animal cells are grown in suspension or on microcarriers. The use of disposable devices have been implemented in all three stages of biotechnological production processes: (i) upstreaming, (ii) downstreaming as well as (iii) final formulation and filling. The majority of applications are to be found in upstream processing. Here, disposable expendable laboratory items, simple peripheral elements, and equipment for unit operations are well-established. Among the components listed, disposable Bioreactors have achieved the highest growth rate over the last year.

    Following an introduction in which the term “single-use” is defined, a general overview of single-use devices in antibody production processes is given. We focus on frequently used disposable bioreactor types, their characteristics, and obtainable results, and discuss apparent trends for disposables in antibody manufacture.

    Keywords:

    characteristics;
    disposable system overview;
    downstream processing;
    membrane bioreactor;
    orbitally shaken bioreactor;
    stirred Bioreactors;
    terminology;
    upstream processing;
    wave-mixed Bioreactors

  • Disposable Bioreactors: the current state-of-the-art and recommended applications in biotechnology
    Applied Microbiology and Biotechnology, 2010
    Co-Authors: Regine Eibl, Stephan Kaiser, Renate Lombriser, Dieter Eibl

    Abstract:

    Disposable Bioreactors have increasingly been incorporated into preclinical, clinical, and production-scale biotechnological facilities over the last few years. Driven by market needs, and, in particular, by the developers and manufacturers of drugs, vaccines, and further biologicals, there has been a trend toward the use of disposable seed Bioreactors as well as production Bioreactors. Numerous studies documenting their advantages in use have contributed to further new developments and have resulted in the availability of a multitude of disposable bioreactor types which differ in power input, design, instrumentation, and scale of the cultivation container. In this review, the term “disposable bioreactor” is defined, the benefits and constraints of disposable Bioreactors are discussed, and critical phases and milestones in the development of disposable Bioreactors are summarized. An overview of the disposable Bioreactors that are currently commercially available is provided, and the domination of wave-mixed, orbitally shaken, and, in particular, stirred disposable Bioreactors in animal cell-derived productions at cubic meter scale is reported. The growth of this type of reactor system is attributed to the recent availability of stirred disposable benchtop systems such as the Mobius CellReady 3 L Bioreactor. Analysis of the data from computational fluid dynamic simulation studies and first cultivation runs confirms that this novel bioreactor system is a viable alternative to traditional cell culture Bioreactors at benchtop scale.

  • disposable Bioreactors for plant liquid cultures at litre scale
    Engineering in Life Sciences, 2009
    Co-Authors: Regine Eibl, Soren Werner, Dieter Eibl

    Abstract:

    Driven by the demands of the market and the manufacturing industry, disposable Bioreactors have gained in importance in cell culture-based processes during the last 10 years. Today they are widely accepted in R&D and also in manufacturing where process simplicity, safety and flexibility have top priority. Although disposable Bioreactors are mainly used for cell expansions, glycoprotein secretions and virus generations realised with mammalian and insect cell lines, there are several reports delineating their suitability for the cultivation of plant cell and tissue cultures. This review describes the current disposable bioreactor types suitable for growing plant cell suspensions and organ cultures (hairy roots, meristematic clusters, somatic embryos) at Litre-scale. Based on a definition of the term ‘‘disposable bioreactor’’, a categorisation of the prevalent types for plant liquid cultures is presented. We describe the bioreactor regimes, working principles and bioengineering parameters of mechanically and pneumatically agitated bag Bioreactors, which have advantages of process scalability and efficiency. Furthermore, results from the literature and data from our own research (obtained during production of undifferentiated bioactive cells, expressions of secondary metabolites and glycoproteins, and micropropagations of plant tissues) are discussed.

Regine Eibl – One of the best experts on this subject based on the ideXlab platform.

  • Encyclopedia of Industrial Biotechnology – Antibody Manufacture, Disposable Systems
    Encyclopedia of Industrial Biotechnology, 2010
    Co-Authors: Regine Eibl, Dieter Eibl

    Abstract:

    The growing demand for biotherapeutics and, in particular, antibodies has resulted in an increasing use of disposables over the last ten years. This concerns both, process development and commercial manufacturing, where animal cells are grown in suspension or on microcarriers. The use of disposable devices have been implemented in all three stages of biotechnological production processes: (i) upstreaming, (ii) downstreaming as well as (iii) final formulation and filling. The majority of applications are to be found in upstream processing. Here, disposable expendable laboratory items, simple peripheral elements, and equipment for unit operations are well-established. Among the components listed, disposable Bioreactors have achieved the highest growth rate over the last year.

    Following an introduction in which the term “single-use” is defined, a general overview of single-use devices in antibody production processes is given. We focus on frequently used disposable bioreactor types, their characteristics, and obtainable results, and discuss apparent trends for disposables in antibody manufacture.

    Keywords:

    characteristics;
    disposable system overview;
    downstream processing;
    membrane bioreactor;
    orbitally shaken bioreactor;
    stirred Bioreactors;
    terminology;
    upstream processing;
    wave-mixed Bioreactors

  • Disposable Bioreactors: the current state-of-the-art and recommended applications in biotechnology
    Applied Microbiology and Biotechnology, 2010
    Co-Authors: Regine Eibl, Stephan Kaiser, Renate Lombriser, Dieter Eibl

    Abstract:

    Disposable Bioreactors have increasingly been incorporated into preclinical, clinical, and production-scale biotechnological facilities over the last few years. Driven by market needs, and, in particular, by the developers and manufacturers of drugs, vaccines, and further biologicals, there has been a trend toward the use of disposable seed Bioreactors as well as production Bioreactors. Numerous studies documenting their advantages in use have contributed to further new developments and have resulted in the availability of a multitude of disposable bioreactor types which differ in power input, design, instrumentation, and scale of the cultivation container. In this review, the term “disposable bioreactor” is defined, the benefits and constraints of disposable Bioreactors are discussed, and critical phases and milestones in the development of disposable Bioreactors are summarized. An overview of the disposable Bioreactors that are currently commercially available is provided, and the domination of wave-mixed, orbitally shaken, and, in particular, stirred disposable Bioreactors in animal cell-derived productions at cubic meter scale is reported. The growth of this type of reactor system is attributed to the recent availability of stirred disposable benchtop systems such as the Mobius CellReady 3 L Bioreactor. Analysis of the data from computational fluid dynamic simulation studies and first cultivation runs confirms that this novel bioreactor system is a viable alternative to traditional cell culture Bioreactors at benchtop scale.

  • disposable Bioreactors for plant liquid cultures at litre scale
    Engineering in Life Sciences, 2009
    Co-Authors: Regine Eibl, Soren Werner, Dieter Eibl

    Abstract:

    Driven by the demands of the market and the manufacturing industry, disposable Bioreactors have gained in importance in cell culture-based processes during the last 10 years. Today they are widely accepted in R&D and also in manufacturing where process simplicity, safety and flexibility have top priority. Although disposable Bioreactors are mainly used for cell expansions, glycoprotein secretions and virus generations realised with mammalian and insect cell lines, there are several reports delineating their suitability for the cultivation of plant cell and tissue cultures. This review describes the current disposable bioreactor types suitable for growing plant cell suspensions and organ cultures (hairy roots, meristematic clusters, somatic embryos) at Litre-scale. Based on a definition of the term ‘‘disposable bioreactor’’, a categorisation of the prevalent types for plant liquid cultures is presented. We describe the bioreactor regimes, working principles and bioengineering parameters of mechanically and pneumatically agitated bag Bioreactors, which have advantages of process scalability and efficiency. Furthermore, results from the literature and data from our own research (obtained during production of undifferentiated bioactive cells, expressions of secondary metabolites and glycoproteins, and micropropagations of plant tissues) are discussed.

Katrin Zeilinger – One of the best experts on this subject based on the ideXlab platform.

  • scaling down of a clinical three dimensional perfusion multicompartment hollow fiber liver bioreactor developed for extracorporeal liver support to an analytical scale device useful for hepatic pharmacological in vitro studies
    Tissue Engineering Part C-methods, 2011
    Co-Authors: Katrin Zeilinger, Jörg C. Gerlach, Thomas Schreiter, Malin Darnell, Therese Soderdahl, Marc Lubberstedt, Birgitta Dillner, Daniel Knobeloch, Andreas K Nussler, Tommy B Andersson

    Abstract:

    Within the scope of developing an in vitro culture model for pharmacological research on human liver functions, a three-dimensional multicompartment hollow fiber bioreactor proven to function as a clinical extracorporeal liver support system was scaled down in two steps from 800 mL to 8 mL and 2 mL Bioreactors. Primary human liver cells cultured over 14 days in 800, 8, or 2 mL Bioreactors exhibited comparable time-course profiles for most of the metabolic parameters in the different bioreactor size variants. Major drug-metabolizing cytochrome P450 activities analyzed in the 2 mL bioreactor were preserved over up to 23 days. Immunohistochemical studies revealed tissue-like structures of parenchymal and nonparenchymal cells in the miniaturized bioreactor, indicating physiological reorganization of the cells. Moreover, the canalicular transporters multidrug-resistance-associated protein 2, multidrug-resistance protein 1 (P-glycoprotein), and breast cancer resistance protein showed a similar distribution patt…

  • effect of human patient plasma ex vivo treatment on gene expression and progenitor cell activation of primary human liver cells in multi compartment 3d perfusion Bioreactors for extra corporeal liver support
    Biotechnology and Bioengineering, 2009
    Co-Authors: Eva Schmelzer, Jörg C. Gerlach, Kerim Mutig, Petra Schrade, Sebastian Bachmann, Katrin Zeilinger

    Abstract:

    Cultivation of primary human liver cells in innovative 3D perfusion multi-compartment capillary membrane Bioreactors using decentralized mass exchange and integral oxygenation provides in vitro conditions close to the physiologic environment in vivo. While a few scale-up Bioreactors were used clinically, inoculated liver progenitors in these Bioreactors were not investigated. Therefore, we characterized regenerative processes and expression patterns of auto- and paracrine mediators involved in liver regeneration in Bioreactors after patient treatment. Primary human liver cells containing parenchymal and non-parenchymal cells co-cultivated in Bioreactors were used for clinical extra-corporeal liver support to bridge to liver transplantation. 3D tissue re-structuring in Bioreactors was studied; expression of proteins and genes related to regenerative processes and hepatic progenitors was analyzed. Formation of multiple bile ductular networks and colonies of putative progenitors were observed within parenchymal cell aggregates. HGF was detected in scattered cells located close to vascular-like structures, expression of HGFA and c-Met was assigned to biliary cells and hepatocytes. Increased expression of genes associated to hepatic progenitors was detected following clinical application. The results confirm auto- and paracrine interactions between co-cultured cells in the bioreactor. The 3D bioreactor provides a valuable tool to study mechanisms of progenitor activation and hepatic regeneration ex vivo under patient plasma treatment.