SBIR Phase II: A Bioprocessing System to Isolate and Purify Therapeutic Antibodies Directly from Cell Culture.

The broader impact of this Small Business Innovation Research (SBIR) Phase II project is to enable the manufacturing of novel lifesaving biologics, reduce the high manufacturing cost of current biologics, and improve their quality by significantly simplifying their purification using a nanoparticle-based technology. Current technologies require time-consuming harvest-clarification steps that are a prerequisite for traditional purification processes and require expensive cleaning and storage validations so that the costly purification resin can be stored for reuse. This technology eliminates the harvest-clarification step completely and its fast purification allows small amounts of resin to be fully utilized within a single batch so that it can be disposed of at the end. In addition, current purification technologies have minimal product recoveries when purifying viral vectors for gene therapy manufacturing. Improved purification of viral vectors with this technology may enable mass commercialization of cell and gene therapies and other novel therapies. This platform technology has applications beyond the manufacturing of biologics, such as a medical device to isolate antibodies from human blood, remove circulating toxins from human blood, and isolate therapeutic antibodies against novel pathogens or biothreats from immunized animals. The proposed project aims to address key downstream challenges associated with the manufacturing of biologics. While upstream processes have improved product titers to reduce the cost of biologics, there are no efficient solutions to manage harvest clarification that is required prior to the chromatography process. Furthermore, current-industry-standard porous chromatography is unsuitable for the purification of viruses and viral vectors. The goal of this project is to scale up the novel media and develop disposables and an automated prototype system to demonstrate direct purification of monoclonal antibodies from challenging cell cultures that cannot be processed efficiently with current technologies. In addition, the purification cycle time will be reduced such that Protein A media can be recycled 50 times in a day and discarded, removing the need for storage. The media will be further characterized and improved, and a cGMP-compliant single-use manifold will be developed. The prototype system will perform all process steps based on the parameters provided by the user and the information from the sensors. The system may be able to purify about 50 grams of monoclonal antibodies with 10 to 20 times less media than current chromatography systems while providing a better-quality product and not requiring harvest clarification. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.