A fermenter holding thousands of liters stands in front of you — a scale no startup can afford on its own. Yet at some facilities, a different problem surfaces once talks about using the equipment begin. The hardware is there, but there are not enough specialists who understand the process and can run pilot production alongside the company, leaving corporate researchers to operate the equipment themselves. The facility has been found, but the burden of proving the process still falls on the company.
In my previous column, I argued that turning precision fermentation-based bio-manufacturing into an industry requires public pilot infrastructure. That infrastructure includes not only buildings and equipment but also a specialist team to operate and maintain them and to validate companies' processes. Only when equipment and an operating team are in place together does a pilot base become something companies can actually use.
Korea does have sites equipped with fermenters of several thousand liters and other facilities, centered on techno-parks and regional support agencies in the biotechnology field. Some institutions have secured specialists and provide solid support for corporate pilot work. But what struck me while visiting numerous institutions to pursue commercialization is that quite a few have thin operating staff and support systems relative to their equipment.
At some of the institutions I visited, researchers from the user company had to operate the fermenter themselves. It is only natural for a company to understand its process well and take part in the pilot work. But the burden grows heavy if it must also handle operating unfamiliar equipment and responding to problems on site. A startup with few research and development staff has to dispatch people to learn how to run the equipment and carry out pilot production as well. Whether a company can work with a professional operating team determines whether the facility is usable in practice.
At some sites, the maintenance condition of the equipment was disappointing, and operating staff were too few for the scale of the hardware. Circumstances differ by institution, but such problems cannot be solved by the effort of individual staff members alone. When a small number of people manage multiple pieces of equipment while also supporting companies, delays are inevitable. Institutions should ask themselves whether they secured the necessary personnel and operating funds at the same time they brought in the equipment.
Running a fermenter requires skilled technique. Oxygen supply, agitation speed and nutrient feeding conditions must be adjusted according to the characteristics of the microorganism and the product. Equipment inspection, verification of sterile conditions and response to abnormalities during operation also matter. Even with identical equipment, the stability of a test and the reliability of its data can vary depending on who manages and operates it.
The same applies to separation and purification after fermentation. Owning filtration, concentration and purification equipment is one thing; running it as a single integrated process is another. Operating conditions must be set to match the characteristics of the product, and the causes of losses must be identified and reflected in the next test run. Those handling fermentation and downstream processing need to understand the entire process together and build up experience.
Belgium's Bio Base Europe Pilot Plant is a case worth studying. There, skilled engineers, operators and technicians support companies in process development and scaling up production. They also carry out experimental design, process analysis and mass and energy balance calculations. The company provides the technology, while the institution's specialist team runs the pilot work based on its experience with equipment and process operation.
Cooperation takes place through projects contracted directly with companies or through publicly funded joint research programs. Not all costs are covered, but the plant has an organization in place to develop corporate needs into concrete projects and execute them. In June this year, it also disclosed a partnership with BASF to scale up production of feed enzymes. When equipment and operating capability are combined, the result can be an industrial base that even large companies use.
Singapore also has a system linking equipment with expertise. A joint laboratory run by the Singapore Institute of Food and Biotechnology Innovation (SIFBI), under the Agency for Science, Technology and Research (A*STAR), and ScaleUp Bio supports 100-liter fermentation, separation and purification, and analysis. Production can then be scaled up by moving to ScaleUp Bio's facilities of up to 10,000 liters. ScaleUp Bio is a joint venture between ADM and Nurasa, a unit of Temasek.
There is also a platform supporting safety and regulatory work. The Future Ready Food Safety Hub (FRESH) is a research and advisory platform established jointly by A*STAR, the Singapore Food Agency (SFA) and Nanyang Technological University (NTU). It provides advisory and research services on safety assessment and supports scientific discussion between companies and regulators. It helps companies build the evidence to demonstrate safety, but final review and approval rest with the SFA.
The procedures I have experienced in Korea involving living modified organisms (LMOs) are another issue worth examining. The burden is heavy, because companies must identify and prepare the required documents and preparatory steps themselves. I plan to examine my experience on the ground and the support needed in my next column.
In a recent discussion on a precision fermentation infrastructure project where I served as a committee member, a point raised by another reviewer resonated deeply. The plans needed to spell out in greater detail who would take charge of operations and how companies would be supported, relative to the targets set for building facilities and installing equipment, as well as how operating costs would be covered once the project ended. As someone who has gone from site to site negotiating access to facilities, I agreed strongly.
There must be no gap between the completion of a facility and the start of support for companies. When drawing up equipment procurement plans, institutions should also set the composition of the operating team, hiring, training and commissioning schedules. If the person responsible for operations takes part from the equipment selection and installation stages, processes suited to corporate needs and maintenance methods can also be reviewed in advance. Preparation for operations must not be put off until after construction is complete.
Roles required for fermentation, separation and purification, analysis and quality verification, safety management and maintenance should be divided up, with personnel secured for each. Assigning multiple functions to a handful of people makes stable operation difficult. A project manager is also needed to agree on test goals and schedules and to explain the results. Only when each person collaborates do individual machines connect organically into a single pilot process.
Conditions that allow skilled staff to stay for the long term matter as well. Learning equipment and processes takes time, and the experience accumulated through repeated operation becomes an asset of the institution. Expertise and experience are hard to build up under a structure in which staff disperse once a short-term project ends. Labor and training costs for stable employment and the transfer of skills should be reflected in operating plans.
Operating costs are another core challenge. Beyond labor costs, there are continuing expenses for electricity, water, consumables, inspection, calibration and repairs. It must be designed in advance which costs will be covered by user fees and which by public funding, and how operations will continue once the construction project ends. If institutions try to recover all costs from user fees from the outset, charges could rise to levels startups cannot bear.
In systems to support companies, equipment rental and pilot services provided by a specialist team should be treated separately, with clear boundaries of responsibility. Roles should be assigned for each party, from process review and test planning through operation, analysis and reporting of results. Corporate researchers and the operating team must be able to collaborate on the strength of their respective expertise.
Performance should also be assessed not only by the number of machines installed but by what pilot services those machines can deliver. Assessments should check whether a specialist team has been secured, whether the equipment is properly maintained and whether requested pilot work was carried out on the promised schedule and to the promised quality. Only as an operating track record builds up can companies entrust follow-up tests with confidence.
Investment in precision fermentation infrastructure must be a project that puts in place not only buildings and equipment but also the team to operate them. The seed-money role of the central and local governments should likewise support continued operation, not just the construction of infrastructure. Securing the people who will take responsibility for a fermenter holding thousands of liters is as important as installing it. The next project proposal should spell out not only what equipment will be brought in but also who will carry out pilot work for companies.
He is...
He holds a B.S., M.S. and Ph.D. in chemical and biomolecular engineering from KAIST and completed postdoctoral research (adviser: Lee Sang-yup).
Former senior researcher, CJ CheilJedang Biotechnology Research Institute
Former head of Korea R&D, PhAST Diagnostics
Former director of research, GF Fermentech
Currently CEO of SilicoBio and research associate professor at KAIST's Bioprocess Engineering Research Center