kLa as a predictor for successful probe-independent mammalian cell bioprocesses in orbitally shaken bioreactors

The aim of this study was to gain a better understanding of orbitally shaken bioreactors (OSRs) operated without controllers for pH and dissolved oxygen (DO) concentration. We used cylindrical OSRs with working volumes ranging from 250 mL to 200 L to determine that the volumetric mass transfer coefficient of oxygen (kLa) is a good predictor of the performance of OSRs at different scales. We showed that kLa values of 7–10 hour−1 were required to avoid DO limitations and to prevent conditions of low pH during the cultivation of CHO cells. Overall, cell cultures in probe-independent OSRs of different nominal volumes ranging from 250 mL to 200 L achieved similar cell densities, recombinant protein concentrations, and pH and DO profiles when having the same kLa. We conclude that kLa is a key parameter for probe-independent bioprocesses in OSRs and can be used as a scale-up factor for their operation.

► The kLa is a good predictor of the performance of orbitally shaken bioreactors. ► kLa of 7–10 hour−1 were required to avoid DO or pH limitations during CHO cell cultivation. ► Probe-independent OSRs from 250 mL to 200 L with the same kLa achieved similar yields.