Tech ReviewA field that’s setting a tremendous pace
12.05.10Rising yields from biomanufacturing processes are opening up new avenues in upstream processing, especially when it comes to mammalian cell culture technology. This EuroBiotechNews biomanufacturing special (pages 32-44) trains the spotlight on new developments in the field, among them decreasing volume demands for biomanufacturing processes , the use of disposable materials or new media and the fresh challenges facing downstream processing . With the hype surrounding the sustainable production of fine chemicals, industrial biotechnology has continued to gain in importance – a fact demonstrated by the establishment of the first industrial-scale plant for succinic acid production to make use of a carbon dioxide consuming fermentation process.
Driven by increasing product titres of up to 20g/L, biomanufacturing scales aren’t necessarily rising – in many cases they’re actually dropping. That’s driving the move towards disposable equipment such as bioreactors, which offer the benefits of both reduced effort when it comes to cleaning/cleaning validation and lower investment costs. In areas like microbial fermentation however using disposables often limits scale. The largest systems on the market that have the necessary mass and energy transfer rates required for the cultivation of bacteria and yeasts are in the 200-500L range (wave-mixed: Biostat Cultibag RM, WaveBioreactor, stirred; XDR-DSTB microbial). The largest disposable system for animal cell culture, which is mostly used in the manufacture of recombinant proteins and antibody drugs, has a maximum volume of 2,000L (XDR-DSTB, animal). Other factors besides scalability that are currently slowing market adoption are limited experience in using such bioreactors, insufficient strength of the plastic material used, high cost for consumables, and the detection of leachables and extractables that could potentially interact with the product.
Trend to stirred disposable bioreactors
Stirred systems are the gold standard with classic stainless steel bioreactors, and market adoption of stirred disposable bag bioreactors has been very strong since its late market entry in 2006. Aside from stirred systems for small and mid-scale production such as the S.U.B., Biostat Cultibag STR, Nucleo Bioreactor and XDR-DSTB, wave-mixed systems such as the Biostat Cultibag RM Wave Bioreactor are available up to 500L, and are dominating seed inoculum production. New systems with two-dimensional platform movement promise to improve the volumetric oxygen transfer rates, and thus expand the disposable bag systems to processes with even higher oxygen demands.
The new developments in upstream processing and formulation are proving a challenge for current product purification methods. It remains to be seen whether in the longer term other techniques such as protein crystallisation will augment current standards like chromatography and filtration.