June 1, 2010 (Vol. 30, No. 11)

Ilene Schneider

Bioengineering Touts Customized Stainless Steel Systems as Benefiting Bottom Line & Environment

Can technology that is environmentally friendly be equally friendly to the bottom line? Bioengineering in Wald, Switzerland, believes it can.

The company has been making stainless steel fermentors since 1972, at which time no such equipment was available for most applications, according to professor Sebastian Niklaus, quality unit manager. “Product development meant just making what was needed. Today product development is a complex, interdisciplinary, and time-consuming process,” he says.

“Our approach is efficiency with resources and consciousness concerning waste. That has always been a concern for the founders of Bioengineering. Switzerland is conscious of environmental issues, so green technology came naturally.”

“Customer-specific, upgradable steel fermentors represent progress,” adds Karin Koller, scientific assistant. “Sustainability means resourcefulness, as well as developing the innovation to ensure product quality, enhance product yields, and thus ensure economic success.”

Dr. Niklaus notes that the current product line includes fermentors and equipment from the laboratory, pilot, and up to production scale for microbial, cell culture, and extremophile applications. “The emphasis, however, is on customized equipment and professional production applications.” 

The bioengineering division of the company designs and builds customized fermentation and cell-cultivation plants. The bioequipment division manufactures standard equipment for fermentation and cell cultivation from lab to pilot scale. Vessel sizes from 1 to 3,000 L facilitate the upscaling of newly developed processes in several steps up to the actual production scale.

Reactor types include airlift fermentors, photo bioreactors, enzyme membrane reactors, fluidized bed reactors, high-pressure/high-temperature fermentors, loop safety fermentors, NMR reactors, solid substrate fermentors, or cell culture reactors. Bioequipment also provides a full range of peripherals, fermentation accessories, probes and measuring systems, components, and spare parts.

Individual, process-oriented design of automation and control systems is the task of the biocontrol division, which designs fully automated high-tech plants equipped with high-precision measurement and control technology.

BioQS develops and complements the quality assurance manual, prepares the validation protocols, and monitors their application in practice.

The key to success, says Dr. Niklaus, has been stainless steel fermentors that have proven themselves over the years. The modular components make the fermentors easy to upgrade, thus improving production processes in a sustainable way. While some people argue that disposable fermentors require less cash outlay and installation time and eliminate cleaning requirements, Dr. Niklaus maintains that an integrated, modular stainless steel fermentation system has a number of advantages.


Bioengineering’s bioequipment division manufactures standard equipment for fermentation and cell cultivation from lab to pilot scale.

Benefits of Stainless Steel

“Stainless steel fermentors do not have the production volume, mass, and heat-transfer limitations of disposable fermentors,” he explains. “Stainless steel plants include piping and transfer lines, while disposables require employees to do the transfer, posing safety risks for employees and product losses when employees make mistakes.”

“A stainless steel production system runs day and night with just a specialist checking some process data, while a disposable production line requires employees walking between fermentors and carrying around dangerous and expensive intermediates.

“SIP and CIP processes become unnecessary with disposable fermentors, reducing chemical, water, and energy consumption and facilitates validation. The process seems to be much less complicated,” Koller says. “On the downside, are the increased operational costs, the high output of waste in the form of plastic bags, possible leaching of extractables, and reduced possibilities for process control.”

She describes several ways to help ensure the highest possible biotechnology yields with the smallest expenditure of time and money. “One approach is to enhance product formation rates by creating optimum conditions for bacterial or cell cultures using feedback control, addition of inducers, or controlled process management.

“Another approach is the utilization of more productive organisms. Extremophile and marine microorganisms have yielded promising results, from the production of enzymes for detergents to the development of drug delivery systems. Genetically manipulated bacteria generate high product yields either directly or in the form of inclusion bodies that provide pure products after refolding. If correct glycosylation of proteins is required, genetically modified yeast can be a more productive alternative to cell culture,” Koller says.

“A third approach is biotransformation for the production of high-value molecules and bulk products that previously could be manufactured only in an expensive multistep chemical synthesis.” Each of these approaches requires exactly defined culture conditions and special equipment and control systems for creating them. The system is “designed to suit the requirements of the processes developed in the laboratory” and to “operate for many years.”

Because it is difficult to anticipate future requirements, all of Bioengineering’s bioreactors are of modular design, including hardware and software. Koller gives examples, including the rotorfilter for the perfusion of cell cultures, the fixed-bed insert for adherent cells, and the methanol control system for protein expression in methylotrophic yeasts. She explains that all steel components in Bioengineering glass fermentors can be replaced with the high-performance thermoplastic PEEK for the refolding of inclusion bodies and the cultivation of marine microorganisms.

Transferring the laboratory process to production scale is easier with stainless steel bioreactors as well, according to Koller, because data such as hydrodynamic characteristics have been collected for decades. “Automated steel bioreactors have highly developed, complex control technology with data analysis, feedback control, and individual process management, combined with components specially selected or even custom-made for the process to enable the maximization of product yields. A high degree of automation decreases labor input and failures caused by human errors.”

Requirements for sterilization, CIP, and validation remain a disadvantage compared to disposable bioreactors. Consumption of resources and residual risk of cross-contamination in multipurpose plants are the main arguments against steel fermentors. However, fully automated systems, recycling, constant monitoring of solutions, efficient cleaning, and sophisticated documentation minimize contamination and consumption issues.

“In addition to regulatory trends, there is a strong tendency toward individually optimized process control comprising the integration of new technology, such as intelligent sensors, as well as optimizing the hierarchy and structure of process control,” Dr. Niklaus notes.

Where does Bioengineering go from here? “Our specialty is to customize. In five years that will continue to be our direction.”

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