Bioreactors are essential tools for the food and pharmaceutical industries. They are used in fermentation, to produce alcohol, and convert raw materials like corn into useful by-products such as ethanol by food manufacturers. Biopharmaceutical companies also exploit bioreactors for production of biologics, vaccines, and antibodies. The main advantage of using bioreactors is scalable manufacturing. Commercially available stirred tank bioreactors can contain up to 20,000 L of volume. Equipped with aeration, impellers, and sensors to ensure efficient nutrient diffusion and waste product removal, such bioreactors have been key to provide reliable supplies of key ingredients and life-saving medical products.
However, large-scale production may not always be suitable and, arguably, is only necessary when there is a concomitant supply of a product. Benchtop bioreactors—which are cheaper to buy, install, and maintain—make use of fewer raw materials and occupy less physical footprint. These benefits make benchtop bioreactors a better choice for many companies, start-ups, and academic labs testing initial ideas and optimizing their production recipes. Here, we describe how benchtop bioreactors can be used in a cost-effective manner for novel applications in the food and pharmaceutical industries.
Synthetic meat production
Synthetic meat, also known as cultured meat, is a type of animal-free meat alternative that has recently become a hot area of research. Some of the reasons motivating the growth of this industry include high environmental cost of cattle rising, emergence of multi-drug resistant microbes due to overuse of antibiotics in livestock, and the possibility that such designer food products can provide better nutrients and are safer to consume.
Synthetic meat is made by seeding muscle (stem) cells into extracellular matrix scaffolds, followed by flowing nutrients into the system and harvesting the tissue layers two to eight weeks later. Most production of synthetic meats is still at the research stage, making benchtop bioreactors an ideal choice to test these initial ideas.
Start-ups and labs wanting to create synthetic meat using cells from various sources and grow tissue layers with different nutrient combinations and flow conditions can take advantage of benchtop bioreactors for cheaper and faster optimization. If such testing is done using conventional large-scale bioreactors, the upfront cost would be significant as such systems are expensive to purchase and maintain. Most importantly, they would consume large amounts of expensive reagents like growth culture serum.
“Before use, researchers need to consider that benchtop bioreactors are not meant to be scaled-down versions of their larger counterparts.”
Although the eventual goal of synthetic meat production is for the consumer meat market, cost savings for start-ups are crucial as most of their research activities are supported by limited funding from grants or investors who are eager to see results. By using smaller benchtop bioreactors, researchers will also be more agile in trying new ideas, giving up on ones that do not work, and identifying optimal formulae for their applications to have an advantage in processes like filing of intellectual properties—a key asset for start-ups. Finally, benchtop bioreactors made of glass and steel are compatible with existing autoclave sterilization protocols due to their compact sizes and do not require dedicated cleaning facilities, leading to additional cost savings.
Personalized cell manufacturing and therapy
Cell therapy is a rapidly growing industry expected to reach a market size of $48 billion by 2027. It involves the introduction of engineered stem or immune cells into patients for application in regenerative medicine and cancer immunotherapy. As of today, there are three FDA-approved cell therapy products such as Kymriah® from Novartis, a type of chimeric antigen receptor T cell (CAR-T) product and a few hundred ongoing CAR-T clinical trials.
Similar to the synthetic meat industry, most of the cell manufacturing industry is still at the research phase and many novel cell therapy products are only being produced at university-affiliated labs and clinics. Most importantly, many of these products are autologous, which means that they are personalized to each patient, making benchtop bioreactors more attractive for manufacturing.
For CAR-T therapy, an average patient would require about 108 cells/dose—a quantity that can be managed by a benchtop bioreactor. Due to its smaller size, more precise control of process parameters like oxygen levels and pH is also possible in benchtop bioreactors. This may help to minimize manufacturing failure to enhance cost savings and reduce treatment delay while boosting product robustness and consistency.
In fact, a number of companies have introduced benchtop-like bioreactors for cell therapy manufacturing. Examples of these instruments include CliniMACS Prodigy from Miltenyi and the modular CocoonTM bioreactor from Octane Biotech/Lonza for automated cell production. Bozza and colleagues recently integrated a novel gene delivery system with the CliniMACS Prodigy system for cell production that is compliant with good manufacturing practices (GMP), demonstrating that smaller, benchtop-like bioreactors can also create GMP-grade cell products. This is a key consideration, especially for academic labs and start-ups who need to convince regulators and funders of the safety and commercial viability of their technology.
Considerations and conclusions
There are multiple benefits to using benchtop bioreactors for researchers testing out new ideas and optimizing novel formulae. There are cost savings, as these smaller platforms are cheaper to buy, install, clean, and maintain. In addition, as they are smaller in scale, the amount of expensive consumables being used for each experiment is less. Importantly, companies are also recognizing the value of benchtop bioreactors and have started selling semi- to fully-automated platforms that can produce food- and GMP-grade products with better product consistency. These automated systems with less human interventions and errors can also help minimize failures during manufacturing, leading to additional cost savings.
Before use, researchers need to consider that benchtop bioreactors are not meant to be scaled-down versions of their larger counterparts. This means that users should not expect identical results from benchtop and conventional bioreactors even when parameters like stirring rate, volume, and temperature are scaled proportionately. This is because the physics of mass and heat transfers are complex and are interdependent in a non-linear fashion. However, data from benchtop bioreactors is still an excellent (and cost-effective) starting point for users developing new bioproduction system or cell manufacturing protocol. With increasing advances in computer simulations, artificial intelligence, and data collection through smart sensors deployable in bioreactors, it is hopeful that results from benchtop bioreactors can one day be directly translatable to larger bioreactors.