Linear Scalability of Virus Production in Integrity iCELLis Single-Use Fixed-Bed Bioreactors, From Bench Scale to Industrial Scale

S. Knowles (, J.C. Drugmand, S. Dubois, Y. Dohogne, F. Debras, N. Havelange, J. Castillo


Over the past decade, single-use bioreactors have been developed and accepted for cGMP use in the biomanufacturing industry. Among
them is the Integrity® iCELLis® series of bioreactors from ATMI LifeSciences, were designed for adherent cell culture.

Adherent cell processes for production of biomolecules and viruses often involve 2-D vessels (e.g. roller bottles, Cell Stacks/Cell Factories, etc.)
requiring many manual operations and large areas of cleanroom space, or microcarrier cultures which require complex cell transfer steps and a
very high level of expertise. Some cell culture processes allowing continuous production by medium perfusion also use adherent cells retained in
a bioreactor while culture media is continuously perfused.

In order to maximize surface area within a compact space and retain cells for easy medium exchange, the iCELLis bioreactors contain macrocarriers
trapped in a fixed-bed providing a 3-D matrix for the cells to grow. These bioreactors also enable precise temperature, pH and dissolved
oxygen control which cannot be done in 2-D cultures.

The iCELLis technology can be used at small and large scales with straightforward process scale-up, easy single-use operations and minimal
space requirement.

Here we present a summary of adherent cell process developments in iCELLis bioreactors, including:

  • HEK 293 cell expansion for production of adenovirus
  • MVA virus production in CEF cells
  • Bovine Herpes Virus production in MDBK cells
  • Recombinant Adeno-Associated Virus in A549 cells
  • Adenovirus production in A549 cells
  • Influenza virus production in Vero cells
  • Paramyxovirus production in Vero cells
  • Undisclosed lytic virus in Vero cells

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