Orbitally shaken bioreactors for mammalian cell culture : engineering characterization and bioprocess scale-up

Driven by the commercial success of recombinant biopharmaceuticals, there is an increasing demand for novel, cost-effective mammalian cell culture bioreactor systems for the production of biologicals requiring mammalian protein processing. Recently, orbitally shaken bioreactors at scales from a few mLs to 2'000-L have been explored for the cultivation of mammalian cells and are considered to be attractive alternatives to conventional stirred-tank bioreactors because of increased flexibility and reduced costs. Although the choice of geometry of these shaken containers is diverse with the availability of conical (i.e. shake flask), square-shaped, or cylindrical containers, the latter are preferred because more regular and predictable flow patterns are generated at all volumetric scales. The main challenge facing the scale-up of the shaken container is to maintain a moderate oxygen transfer rate (OTR) to meet the oxygen requirement of cultured cells. The volumetric mass transfer coefficient (KLa) of shaken bioreactors with working volumes from a few mLs to 1'000-L were determined, and operating parameters having an impact on the oxygen transfer were investigated. KLa values between 10-30 h-1 were typically achieved in small-scale (