Therefore, for a process to be cost effective, media formulation must be relatively inexpensive. For a 500-L process, that amount of media can easily total tens of thousands of liters over the course of the culture. Unlike batch and fed-batch processes, perfusion processes use a great deal of media -Â one-half to three times the volume of the bioreactor each day. Moreover, some ingredients (and their relative proportions) are critical to productivity and stability. As with fed-batch processes, media for perfusion systems can have as many as 80 ingredients, including amino acids, vitamins, trace elements, and buffering systems. But with a quality by design (QbD) approach, a perfusion production process can be designed and implemented efficiently and cost effectively.
![nova bioprofile 400 nova bioprofile 400](https://docplayer.net/docs-images/56/39550162/images/24-0.jpg)
Additional complexities can come from possible variations in total run time and the need to maintain a sterile system through the seed train and during the time in production culture. Perfusion requires the continuous removal and replacement of cell-culture fluid with fresh media, while maintaining a constant volume in a bioreactor. That said, perfusion is not used as often as it could be for producing biologics, largely because it is more complex to set up than fed-batch processes. Moreover, because a perfusion process is much closer to steady state than is a fed-batch process, it often produces a more consistent product - especially for molecules that are sensitive to changes in conditions inside a bioreactor.
![nova bioprofile 400 nova bioprofile 400](https://checkout.labx.com/pub/media/catalog/product/4/3/4301676-3_424055_4301676_2970.jpg)
![nova bioprofile 400 nova bioprofile 400](https://i.ebayimg.com/images/g/6YUAAOSwugJefEQ6/s-l640.jpg)
A 2013 study showed that perfusion is more cost effective than fed-batch processes for most combinations of titers and production volumes ( 1). Perfusion manufacturing can provide much higher levels of productivity than fed-batch systems can, thereby reducing production costs. Photo 1: Clones exhibit a number of behaviors, one of which is clumping.Ä«iotherapeutic proteins usually are produced by either fed-batch or perfusion processes.