How Multipurpose is a Disposable Bioreactor? - The authors discuss the use of single-use bioreactors throughout industry. - BioPharm International


How Multipurpose is a Disposable Bioreactor?
The authors discuss the use of single-use bioreactors throughout industry.

BioPharm International
Volume 24, Issue 3, pp. 51-56


Interest in microbial expression systems such as E. coli and Pichia pastoris, is increasing. That's the case not only for traditional products such as enzymes but also for production of biopharmaceuticals and the manufacturing of platform chemicals. Bulk fermentation products are produced on large scales of up to 400 – 800 m3 in stirred bioreactors, but for screening and pre-culture purposes, the single-use bioreactors offer the advantage of fast turnaround, speed in early stage development, and late stage development (scale-down experiments). The limited infrastructure required (no autoclaves or SIP/CIP) is also a key advantage for single-use equipment.

Figure 4. Cultivation of E.coli in a 10 L fed-batch in the CELL-tainer bioreactor. OD550 = biomass concentration in optical density units measured at 550 nm.
Figure 4 shows microbial culture in a 10L fed-batch performed in the CELL-tainer single-use bioreactor. The profile shows results that are comparable with those seen in stirred fermentors up to 100 L working volumes (5).

Figure 5. Single-use dialysis membrane. (COURTESY: TRACE ANALYTICS GMBH/CELLUTION BIOTECH BV.)
In addition to the pH and DO sensor, a device for measuring glucose and lactate is available, using the Trace Analytics ( technology of a dialysis membrane. The dialysis membrane is integrated in the bottom of the bag, comparable to the pH and DO sensors. The device is an integrated part of the gamma-irradiated bag (see figure 5).

Figure 6. Comparison of in-line and on-line glucose measurement in an E.coli culture using the ContiTRACE dialysis membrane plug integrated in the CELL-tainer.
In an E. coli fermentation, using glucose as substrate, online and offline data are compared (see figure 6). There is only a slight, negligible discrepancy between on-line and off-line data. The off-line data are based on an enzymatic method in collected samples using an autosampler. The discrepancy is easy to explain: the off-line data show lower values because of the metabolic activity that continues after a sample till analysis takes place (2–5 minutes before the sample is –5 C). The online measurements are highly accurate because there is continuous equilibrium between the culture and the cell-free dialysate. The ability of online measurement of an important parameter such as glucose (and lactate) offers the possibility to develop advanced on-line control strategies, thus making the single-use bioreactor increasingly suitable for process development.


Figure 7. Relative operational cost comparison of 15-L bioreactors of different types.
Single-use bioreactors offer the advantage of fast installation, lower investments in infrastructure, and a significant decrease of validation costs. Similarly a comparison of operational costs of a 5-day microbial process as performed in a 15L autoclavable, in a 15L SIP bioreactor, versus the process in the single-use CELL-tainer, reveals significantly lower costs in the single-use system per run (see figure 7). This includes the costs of bags (fully equipped with sensors). Because the single use CELL-tainer bioreactor has a fast turnaround time, in the same bioreactor system, 40% more runs/year can be made, when compared to an autoclavable fermenter.

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