Single-use technology for bioreactors has come a long way during the past 25 years, yet some of its capabilities remain to
be exploited. Equipment manufacturers have adopted the technology as if it were an evolutionary step, but it is, in fact,
revolutionary. Current offerings in single-use technologies often are not presented this way, however.
Single-use bioreactors currently follow one of two general formats. In one of these, the single-use components are used as
linings for stainless-steel tanks. In a second model, a flexible bag is affixed to a rocker system that helps aerate and mix
components inside the bag (1–3). Both of these models limit the value of single use systems, however.
Equipment manufacturers conduct extensive exercises to chart the future of bioprocessing methods, but the real judge of what
is needed is the consumer. The development of large-scale bioreactors for the manufacture of commercial quantities of monoclonal
antibodies and vaccines at an affordable cost and with a short development time would fill an unmet need. Therapeutic Proteins
is looking at ways to meet this demand by incorporating a comprehensive bioprocessing unit capable of upstream and downstream
processing inside a single bag without any moving parts. The company has filed or received dozens of US and worldwide patents
for these inventions. In this way, the company hopes to spur the further evolution of single-use technologies.
Figure 1: A 400-L bioreactor for bacterial fermentation used by Therapeutic Proteins to manufacture filgrastim.
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In this new unit, mixing is achieved by gentle pressing on the bag to create a wave. Figure 1 shows a bioreactor with a flapper
that pushes down on the bag to create a wave motion inside the bag. The bag itself lies flat and does not move. The Navier–Stokes
equations describe the motion of fluid substances, such as liquids and gases (4). These equations state that changes in the
momentum (i.e., force) of fluid particles depend only on the external pressure and internal viscous forces (which are similar
to friction) acting on the fluid. The equations also describe the balance of forces acting at any given region of the fluid.
A force applied to any portion of a fluid would thus be transferred to the rest of the fluid (4). A flexible bag never needs
to be shaken or rocked. All that is needed is to apply a minimal force, a pressure on any part of the bag, to start the motion
of liquid. Rocking and shaking technologies generally fail to account for the physical constraints on the amount of stress
that can be applied to the bag. Bags used in the rocking model cannot hold more than 500 L of media because the bag would
break when rocked at a larger size.
