Published April 30, 2021 | Version v1
Journal article Open

Theoretical justification of selecting a method for cultivation of mammal cells as a basis for designing membrane bioreactors in accordance with the requirements of good manufacturing practice

Creators

  • 1. National Technical University of Ukraine «Igor Sikorsky Kyiv Polytechnic Institute»; Pharmaceutical Corporation Artertium
  • 2. National Technical University of Ukraine «Igor Sikorsky Kyiv Polytechnic Institute»

Description

The object of research is technological cultivation systems, the central element of which are bioreactors, which ensure efficient metabolism of mammalian cells (Metazoa). Fundamental differences in the phenotypic characteristics of mammalian cells from microorganisms and the special phase-hydrodynamic state of the cultivation system form special requirements for the design and operation of bioreactors. One of the most problematic areas in the process of using cell cultures to obtain medicinal products of biological origin is to ensure the correct cultivation conditions in order to obtain the maximum amount of the target product. The quality assurance system for drug production is based on good manufacturing practice, which puts forward a number of general requirements for the organization of production of drugs of specified quality, efficacy and safety.

The study analyzed the phenotypic characteristics of mammalian cells. The analysis of industrial cultivation systems is carried out and a new classification is proposed, which takes into account the phase-hydrodynamic state of the culture and the specifics of the hydrodynamics of the bioreactor. The analysis made it possible to determine membrane cultivation systems as the most promising. The choice of this cultivation system has a number of features, in particular, the provision of favorable conditions during a long process of cultivation of support-dependent cells. This system guarantees a constant and efficient supply of nutrients, including dissolved oxygen, and the removal of waste products. A wide range of materials for the manufacture of membranes allows to use an individual approach to different types of cell lines. Due to this, it is ensured that high cultivation rates are obtained - the density of cells on the growth surface, the provision of the necessary substances during the entire cultivation process without negative mechanical effects on the cells. The modular design of the membrane elements allows for scalability of the cultivation process from laboratory development to industrial cultivation. The results obtained in this work can be the initial data in the study of hydrodynamic and mass transfer characteristics and in the development or construction of new bioreactors, which will reduce the stage of laboratory development and accelerate the introduction of innovative drugs.

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References

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