Current wisdom holds that microbial fermentations—particularly larger production processes—still rely heavily on glass and stainless steel construction. But that is beginning to change. Due to growing demand for single-use products for microbial cultures, Eppendorf has introduced the BioBLU® 0.3f, a 250 mL single-use vessel designed specifically for microbial fermentation. Eppendorf sees market potential for these products, and plans to address growing demand with additional single-use products for fermentation.
Where this will lead remains to be seen, as process developers lack a clear upward scalability path for single-use fermentors. But Mirro is optimistic. “Years of development, and ample comparative data, show process comparability and cell-line compatibility for stainless steel and single-use bioreactors,” he says. He hints that the same factors that justify single use in cell culture processes may one day apply to fermentation, even at large scale.
Gross physical design characteristics for fixed tank bioreactors do not change much: “The basic parameters have been around forever,” notes Jeff Watkins, principal at Blue Star Engineering. Blue Star designs glass and stainless steel bioreactors, as well as single-use systems, for many of the top bioreactor OEMs.
The main variables include the ratio of height to diameter, and matching the impeller and gassing mechanism to the volume, cell type, and process. For mammalian cell cultures, disposable reactors have achieved performance characteristics comparable to stainless, which allows direct scaleup from smaller single-use bioreactors to stainless steel.
What has emerged from design orthodoxy is a keen interest in bioprocessors in process understanding, for monitoring reaction conditions in real time, and employing that information to control the process.
“As processes become more complex, operators watch for more process parameters, to introduce later into their recipes,” Watkins says. “That’s good for us because it indicates that customers want custom-designed systems, not just something off-the-shelf.”
Custom designs are also an option with single-use bioreactors, but there the challenge is incorporating measurement instruments and probes into the bags, before it reaches the customer, without compromising sterility. Most plastic bioprocess containers are sterilized at the manufacturer, and intended for use directly out of the box, with no modification.
“Having customers insert their own sensors goes against the whole idea of presterilization,” Watkins observes. By contrast, users can insert sensors and other devices into glass or stainless reactors, then sterilize the entire assembly in place.