Dynamic single-use bioreactors used in modern scale biotechnological processes

During the past 10 years, single-use bioreactors have been well accepted in modern biopharmaceutical production processes targeting high-value products. Up to now, such processes have mainly been small- or medium-scale mammalian cell culture-based seed inoculum, vaccine or antibody productions.This has even led to the development of new single-use bioreactor types. Moreover, due to safety issues it has become clear that single-use bioreactors are the ‘‘must have’’ for expanding human stem cells delivering cell therapeutics, the biopharmaceuticals of the next generation. So it comes as no surprise that numerous different dynamic single-use bioreactor types, which are suitable for a wide range of applications, already dominate the market today. Bioreactor working principles, main applications, and bioengineering data are presented in this review, based on a current overview of greater than milliliter-scale, commercially available, dynamic single-use bioreactors. The focus is on stirred versions, which are omnipresent in R&D and manufacturing, and in particular Sartorius Stedim’s BIOSTAT family. Results and ConclusionFinally, we examine development trends for single-use bioreactors, after discussing proven approaches for fast scaling-up processes. For the bioprocess controller, first a generalized model with double-substrate limitation was framed. The bioprocess model considered is basically an unsegregated and unstructured model having four bioprocess state variables and four control inputs. The model considered is nonlinear, having time-varying parameters. In addition, the model has a lot of unmodeled dynamics. The only measurable bioprocess variable is the dissolved oxygen concentration.

Keywords:

Computational fluid dynamics , Engineering characteristics , Main applications , Scale-up , Single-use bioreactor types