Systems and methods for scalable manufacturing of therapeutic cells in bioreactors

A large scale suspension-based system for the production of cells grown on microcarriers or as cell aggregates, the system comprising:

• a bioreactor comprising a vessel and a mixer disposed in the vessel, the mixer operably coupled to a drive mechanism and being operated at an agitation rate;
• a suspension comprising cells suspended in a volume of culture fluid disposed in the vessel and being mixed by the mixer, the suspension including a plurality of turbulent eddies generated by the mixer, the plurality of turbulent eddies each having an energy dissipation rate (EDR), wherein a magnitude of the EDR of at least approximately 60%, at least approximately 70%, at least approximately 75%, at least approximately 80%, at least approximately 85%, at least approximately 90%, at least approximately 95%, or at least approximately 97% of the turbulent eddies is less than approximately 0.0015 m2/s3.

Method of production of therapeutic cells grown on microcarriers or as cell aggregates in a suspension-based bioreactor, the method comprising:

• depositing a suspension comprising cells suspended in a volume of culture fluid into a bioreactor,
• setting an agitation rate of a mixer disposed in the bioreactor,
• actuating the mixer at the set agitation rate to mix the suspension in the bioreactor, the suspension including a plurality of turbulent eddies generated by the mixer, wherein a magnitude of an energy dissipation rate (EDR) of at least approximately 60%, at least approximately 70%, at least approximately 75%, at least approximately 80%, at least approximately 85%, at least approximately 90%, at least approximately 95%, or at least approximately 97% of the turbulent eddies is less than approximately 0.0015 m2/s3.

41-54. (canceled)