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Application of Disposable Bag-Bioreactors in Tissue Engineering and for the Production of Therapeutic Agents

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Advances in Biochemical Engineering / Biotechnology

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Abstract

In order to increase process efficiency, many pharmaceutical and biotechnology companies have introduced disposable bag technology over the last 10 years. Because this technology also greatly reduces the risk of cross-contamination, disposable bags are preferred in applications in which an absolute or improved process safety is a necessity, namely the production of functional tissue for implantation (tissue engineering), the production of human cells for the treatment of cancer and immune system diseases (cellular therapy), the production of viruses for gene therapies, the production of therapeutic proteins, and veterinary as well as human vaccines. Bioreactors with a pre-sterile cultivation bag made of plastic material are currently used in both development and manufacturing processes primarily operating with animal and human cells at small- and middle-volume scale. Due to their scalability, hydrodynamic expertise and the convincing results of oxygen transport efficiency studies, wave-mixed bioreactors are the most used, together with stirred bag bioreactors and static bags, which have the longest tradition. Starting with a general overview of disposable bag bioreactors and their main applications, the following paper summarizes the working principles and engineering aspects of bag bioreactors suitable for cell expansion, formation of functional tissue and production of therapeutic agents. Furthermore, results from selected cultivation studies are presented and discussed.

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Abbreviations

AAV:

Adeno-associated virus

ACD:

Aseptic connection device

AD:

Aujeszky’s disease

ADV:

Aujeszky’s disease virus

B cells:

Lymphocytes which produce antibodies against soluble antigens

BEV:

Baculovirus expression vector

BHK cells:

Baby hamster kidney cells

BHV:

Bovine herpes virus

CHO cells:

Chinese hamster ovary cells

CV:

Culture volume

dhfr− :

Dihydrofolate reductase deficient

E. coli:

Escherichia coli

E-FL cells:

Embryogenic feline lung fibroblast cells

FDA:

Food and Drug Administration

G. max:

Glycine max

GMP:

Good Manufacturing Practice

GS-NS0:

Glutamine synthethase deficient mouse cell line

H. muticus:

Hyoscyamus muticus

H. procumbens:

Harpagophytum procumbens

HEK cells:

Human embryogenic kidney cells

HSC:

Haematopoietic stem cells

IgG:

Immunoglobulin

IL-2:

Recombinant interleukin-2

ISO:

International Organization for Standardization

kLa:

Gas-liquid mass transfer coefficient

M:

Motor

M. domesticus:

Malus domesticus

mAb:

Monoclonal antibody

MDBK cells:

Madin-Darby bovine kidney cells

MDCK cells:

Madin-Darby canine kidney cells

MEV:

Mink enteritis virus

MOI:

Multiplicity of infection or optimal ratio of virus particles per cell

N. tabacum:

Nicotiana tabacum

NK cells:

Natural killer cells

NS0 cells:

Mouse myeloma cells

P. ginseng:

Panax ginseng

P. pastoris:

Pichia pastoris

pDNA:

Plasmid DNA

PEI:

Polyethyleneimine

PER.C6™ cells:

Human embryogenic retinoblast cells

PGA:

Polyglycolic acid

PLA:

Polylactic acid

P/V:

Power input per volume

r:

Recombinant

Re:

Reynolds number

rpm:

Revolution per minute

RV:

Rabies virus

S. cerevisiae:

Saccharomyces cerevisiae

SEAP:

Secreted alkaline phosphatase

SeMet:

Selenomethionine

Sf:

Spodoptera frugiperda

T. baccata:

Taxus baccata

T cells:

Thymus cells, belonging to the group of lymphocytes

TCID50 :

Tissue culture infectious dose

TIB:

Temporary immersion bioreactor

Tn5 cells:

Cells from Trichoplusia ni (insect cells, also called High Five® cells)

TOI:

Optimal density of cells at infection

tu:

Transducing units

USP:

United States Pharmacopeial Convention

V. vinifera:

Vitis vinifera

Vero cells:

Kidney epithelial cells from African green monkey

VLPs:

Virus-like particles

VM:

Vibromixer

vvm:

Volume per volume per minute

WIM:

Wave-induced motion

3D:

Three-dimensional

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  1. Zurich University of Applied Sciences, School of Life Sciences and Facility Management, Institute of Biotechnology, Campus Grüntal, Wädenswil, , CH-8820, Switzerland

    Regine Eibl & Dieter Eibl

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  1. Regine Eibl
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Eibl, R., Eibl, D. (2009). Application of Disposable Bag-Bioreactors in Tissue Engineering and for the Production of Therapeutic Agents . In: Advances in Biochemical Engineering / Biotechnology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2008_23

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