No Impellers Needed
PBS Biotech designs and manufactures single-use bioreactors with a twist. According to Daniel Giroux, vp of R&D, duplicating the agitation mechanisms of small reactors in large systems is problematic without subjecting cells to significant shear damage.
PBS’ U-shaped bioreactors employ a patented mixing technology, the Air-Wheel™, that exploits the fact that cell cultures must be oxygenated. Air-Wheel uses the buoyancy of rising gas bubbles to turn the Air-Wheel structure, thus avoiding the need for external actuation of the stirring mechanism.
The result, according to the company, is rapid, homogeneous mixing and a high mass transfer rate with extremely low shear stress on cells.
PBS offers scalability from three liters for lab work, and 80 liters for preclinical and clinical batches. In targeting full-scale GMP production, the company plans to produce a 500 L system later this year, and a 2,500 L bioreactor in 2012.
“Since the mixing mechanism is proportional to the size of the vessel, Air-Wheel works more efficiently as bioreactor volume increases,” explains Giroux, a definite benefit given that mixing is one of scaleup’s biggest challenges.
According to Giroux, traditional bioreactors were designed for steam sterilization—essentially as pressure vessels. “They were never optimized for mixing. Mammalian cell culture reactors were adapted from chemical mixing tanks, which used shaft-and-impeller mixing.”
As bioreactors grew in size, designers were more or less forced to retain the original form factor and stirring mechanism, including impeller design. “Which is why mixing and mass-transfer problems get worse as the size increases.”
Designers of traditional single-use reactors, he says, never fully appreciated that cleaning was unnecessary. Except for Wave, now part of GE, they mostly retained the shape and mechanical characteristics of traditional tanks. “But it becomes difficult to put impellers into the right locations.”
He claims that at three liters, glass or stainless steel reactors exhibit up to ten times as much shear as the PBS bioreactors. “Our shear goes up a bit at higher scale, but very little.” Ditto for mixing time. Time to 95% mixing is claimed to be less than one minute.
“If you have a tool where critical parameters are so similar across all scales, scaleup will be much easier.”
What about cells for which shear is not a problem? Many such lines exist, Giroux says, but for early-stage development lines, where shear sensitivity is unknown, knowing that shear will not be a problem across production scales is no small comfort.