The 1990s and 2000s saw a great increase in single-use technology for upstream production. In addition to the first single-use bags for storage and transport of buffers and media from HyClone (today a unit of Thermo Fisher Scientific), two-compartment membrane bioreactors and the first wave-mixed bag bioreactor system for mammalian cell cultures, the Wave Bioreactor 20, entered the market. The product was developed by Wave Biotech U.S, which was later acquired by GE Healthcare, and Wave Biotech Switzerland, which is now part of Sartorius Stedim Biotech.
Despite their lack of in-line sensors, single-use bioreactors prevailed in cell-expansion projects, screening experiments, and preclinical sample production at lab scale. Studies documented the advantages of wave-induced motion, which was initially viewed with skepticism, in surface-aerated bags manufactured from multilayer films. Positives included lower shear stress acting on cells, the opportunity for direct inoculation with cells pooled from T flasks (omitting intermediate cultivation steps), removal of need to add antifoam, and cost savings of 30–50%.
The Wave Bioreactor 20 and its successful application beyond cell expansion was a driver for the rapid further development of single-use technology in the 2000s.
In addition to aseptic connection devices, new sampling and transfer systems, single-use membrane filters and bioprocess containers, as well as stirred single-use mixers (e.g., LevTech’s Magnetic Mixer), have found their way into the development and commercial manufacture of small- and mid-volume protein therapeutics.
Since 2005 stirred single-use bioreactors have been available from HyClone and Xcellerex (XDR™ Disposable Stirred Tank Bioreactor) in addition to further wave-mixed systems (Tsunami Bioreactor and the AppliFlex from Applikon) for mammalian cells. In addition, all single-use bioreactors operating with bags have been available with optical single-use or standard sensors for in-process control of pH and DO.