Newly patented single-use fermenter developed in the Lehigh Valley

A fermenter is an essential tool for producing vaccines and many other biopharmaceutical products. Though it resembles a sophisticated beer keg, a fermenter is a highly specialized vessel. As cells grow inside, its mechanical parts regulate the interior aeration, oxygen levels, agitation, temperature, pressure levels, and pH.

Since the 1950s, the production of vaccines and pharmaceuticals has increased. As a result, traditional fermenters grew significantly in size. While most hold around 500 liters, some can hold up to 100,000 liters (more than 26,400 gallons) and stand about 11 feet tall. Since these tanks are often used for extended periods, they require regular maintenance and careful assembly. Vertical tanks are often raised off of the floor to allow for these activities, requiring high ceilings, ladders, stairways, and railings to meet OSHA regulations—adding to overall costs.

A recent innovation in this field is the horizontal fermenter, patented by New Horizon Biotech, a privately held biotechnology and biopharmaceutical equipment manufacturer based in Bethlehem, PA. Designed to fit into spaces with lower ceilings, it accommodates all fermenter sizes from 50 to 3,000 liters within a 9-foot height constraint.

“Microbial cells do not care that they are mixing, respiring, doubling, and metabolizing product in a horizontal tank,” says Ernest Stadler, New Horizon Biotech founder and CEO.

A horizontal tank system also offers a greater range of pressurization and modularity, allowing a variety of configurations for specific types of production. Additionally, a horizontal orientation provides more surface area inside the tank, preventing overflow and contamination of the tank exhaust port.

New Horizon Biotech has developed a 50-liter (13-gallon) prototype single-use horizontal fermenter (SUHF) with a disposable fermentation bag that fits inside a stainless-steel bag retention vessel (BRV). Growing the cells in the bag allows for greater pressurization, which can enhance cell growth. The BRV fully encloses the entire bag, and includes ports and support faceplates to prevent bulging and inconsistent performance under pressure. The bag can be pressurized to create the conditions needed for high cell densities, or greater production, to be achieved.

Lehigh researchers used the SUHF at Lehigh University’s Mountaintop Campus and ran experiments to characterize its performance, allowing New Horizon Biotech to accurately represent the performance of its fermenter. Lori Herz, teaching full professor and associate chair of bioengineering at Lehigh University, leads the investigation with co-PIs Angela Brown, associate professor of chemical and biomolecular engineering, and Hugo Caram, professor of chemical and biomolecular engineering. Two master’s students and three undergraduate students also supported the research project.

"This project has provided students with real-world experience learning how to operate a fermenter, run an experiment, and analyze the data, like engineers do in industry,” says Herz. “All of these activities can help students prepare for work in graduate school and future careers.”

Case in point: Lehigh University alum Kevin Callahan (B.S. BIOE ’22, M.S. BIOE ’23) is now a process development scientist at Pfanstiehl Inc.

“The fermenter project I worked on with New Horizon Biotech facilitated my graduate bioengineering studies by complementing class work and offering real-world experience with a local start-up,” says Callahan. “Interfacing with a new and unique fermenter gave me valuable insight into the process of development and prototyping. In addition, working to collect data provided skills in both experimental design and lab techniques. This project was invaluable to my education and something that cannot be replicated in a classroom setting."

The proximity of New Horizon Biotech and Lehigh University in the Bethlehem area benefits researchers at both institutions. New Horizon Biotech gains access to Lehigh’s knowledgeable faculty and students, who, in turn, gain hands-on experience applying their work in real-world settings. Dr. Janice Phillips, Director of Technology at New Horizon Biotech, brings 30 years of experience in fermentation and bioprocess technology commercialization. She also served as a professor in chemical engineering at Lehigh from 1980 to 1999. Meanwhile, 19 undergraduate and master’s students from Lehigh’s Bioengineering and Chemical & Biomolecular Engineering departments have contributed to the development of the horizontal fermenter project.

Lehigh University and New Horizon Biotech are located near the greater Philadelphia biopharma research cluster, one of the top ten in the nation, according to Genetic Engineering & Biotechnology News, contributing to its growth and vitality. Pennsylvania’s robust pharmaceutical and device manufacturing sector is among the top states in bioscience R&D and innovation, patenting, and industry investment. Through PITA collaborations like the partnership between Lehigh and New Horizon Biotech, these successes will continue to drive progress in the Commonwealth.