Bioengineering Parameters for Single‐Use Bioreactors: Overview and Evaluation of Suitable Methods

Abstract

During the past five years, the number of single‐use bioreactors used in biopharmaceutical research and production has increased tremendously. This increase has been particularly associated with mammalian cell culture processes from small‐ to medium‐scale volumes. Even though nowadays customers can choose from a multitude of 2nd and 3rd generation single‐use bioreactors, ranging from mL‐ up to m3‐scale, there is a lack of knowledge of their engineering parameters. Different approaches have been applied to characterization investigations, resulting in an inability to compare different single‐use bioreactors with each other and their reusable counterparts, creating an obstacle to a systematic approach to scaling‐up the process. This article describes parametric, experimental and computer‐based numeric methods for biochemical engineering characterization of single‐use bioreactors, which have already been used successfully for the characterization of their reusable counterparts. For the first time, these methods have been evaluated in terms of their practical application.

Design space definition for a stirred single‐use bioreactor family from 50 to 2000 L scale

“…This is motivated by several advantages of these bioreactors like reduced risk of cross contaminations or shortening lead times [2]. Singleuse bioreactors differ in terms of shape, agitation principle and gassing strategy [3]. Hence, a direct process transfer or scale-up between different systems can be a challenge.…”

Single-Use Bioreactors for Animal and Human Cells

“…Currently SU bioreactors with working volumes of up to 2,000 L are commercially available (Löffelholz et al 2013a). Eibl and Eibl (2010) distinguish between small-volume systems (screening scale), medium-volume systems (benchtop and pilot scale) and large-volume systems (production scale).…”

“…50 L, which were validated by PIV measurements (Löffelholz 2013), revealed that the pitched blade impeller generated a downward pumping axial flow pattern, where the fluid recirculated upwards along the outer walls. Below the impeller, two differentlysized flow loops are induced due to the off-center position of the impeller (Löffelholz 2013a;Löffelholz et al 2013a). Based on the steady fluid flow pattern, a constant power number of Ne ¼ 1.9 was predicted above a critical Reynolds number of 4 · 10 4 (Löffelholz et al 2010).…”

Design space definition for a stirred single-use bioreactor family from 50 to 2000 L scale

“…For the quantification the dimensionless Newton number (Ne) was determined by torque measurements [3]. From the results the power input per volume was calculated for tip speeds between 0.6 and 1.8 m/s.…”