A research team that includes Andrew Zydney, Bayard D. Kunkle Chair and professor of chemical engineering at Penn State, and is led by the University of Delaware's Kelvin Lee has received a three-year, $10.5 million funding award through the Gates Grand Challenges Program aimed at significantly lowering the cost of manufacturing monoclonal antibodies. Penn State's share of the funding is $600,000.
These lab-made proteins work similarly to natural antibodies produced within your body when you catch a cold - your immune system jumps into action, with antibodies working to block and neutralize the virus and marking the invader for destruction by other immune cells.
Monoclonal antibodies (mAbs), however, are designed to target harmful cells with precision, making them powerful tools in treating illnesses such as the flu, cancer, autoimmune diseases like lupus and rheumatoid arthritis, neurological conditions such as multiple sclerosis and even allergic reactions. But creating these therapies is complex and costly.
In addition to Zydney, the project will be carried out by a collaboration of industry and academic partners, including many from the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL). Lee serves as director of NIIMBL, headquartered at the University of Delaware, a public-private partnership of more than 200 member organizations - including industry, academia and government - working to accelerate biopharmaceutical innovation and develop a skilled workforce for the industry. Other key partners on the project include researchers from the University of Delaware, Sartorius, Rensselaer Polytechnic Institute, Enquyst Technologies, Michigan Technological University and University College London.
"I am truly excited to be part of this international collaboration focused on expanding the accessibility of these life-saving drug products," Zydney said. "This is also a great recognition of the contributions that my lab has made, and continues to make, in the development of novel membrane systems for bioprocessing."
While mAb therapies are widely available in the developed world for a range of treatments including infectious diseases, cancers and autoimmune disorders, the complexity of the manufacturing process, stringent regulatory requirements, costly raw materials and significant infrastructure investments means they are prohibitively expensive for those in low- and middle-income countries.
The Grand Challenges are "a family of initiatives fostering innovation to solve key global health and development problems," according to the Gates Foundation Global Grand Challenges website. This Grand Challenge is focused on making an anti-malarial antibody at low cost. The learnings and technology will, however, be applicable to manufacturing all mAbs, Lee said. Globally, 263 million malaria infections and 597,000 deaths from the disease occurred across 83 countries in 2023, according to the World Health Organization.
The project team brings together specialized expertise in cell culture and separation technologies, economic modeling and manufacturing processes. The team will coordinate efforts over the lifespan of the award to test and demonstrate new approaches to mAb manufacturing that can be used as a basis to achieve the "$10 per gram" goal set out by the Gates Grand Challenge.
"We plan to achieve this dramatic reduction in the cost of monoclonal antibody products by re-envisioning both the cell culture used to produce the antibody and the downstream process used to purify the antibody to the levels required for use as a parenteral drug product," Zydney said.
Work in Zydney's lab at Penn State will specifically focus on the purification steps involving the application of membrane technology. This includes the use of membranes to remove host cell proteins as part of an integrated precipitation-filtration process as well as the use of membranes for the removal of any viruses or bacteria that might have inadvertently contaminated the antibody product. According to Zydney, improving the performance and reducing the cost of the membrane systems will be essential for production of these lower cost monoclonal antibody products.
This particular Grand Challenge is in honor of Steve Hadley, former senior program officer at the Gates Foundation, who championed the reduction of mAbs manufacturing costs to make life-saving treatments affordable and accessible.
