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.”