The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to provide analytical technology that will foster the commercial development of complicated biomanufactured products. The most pressing need is to reduce the time and cost to bring the latest generation of biotherapeutic drugs to market. Currently, upwards of eight years and $1B is spent to move a candidate drug from discovery through final approval. Along the way $300M is consumed by analytical testing procedures to certify the product. The American healthcare system will benefit from new and less expensive analytical technologies that reduce certification costs and lead to less expensive drugs. Manufacturing efficiency also can be improved using the proposed technology. Biomanufactured products are harvested from cultured cells, and there are times when the culturing process fails to produce a perfect product. Detecting impurities and spoilage during manufacturing will further reduce manufacturing costs and directly benefit the consumer through the delivery of better therapeutic products and treatment regimens.This SBIR Phase I project proposes to quantify the validity of an ion mobility spectrometer as a high-throughput tool for screening conformational variation, purity, and aggregation of biotherapeutic drugs. Conformation imparts functionality to a protein and any variation in conformation implies there is a variation in biochemical activity, which is undesirable. Ion mobility is a technique that determines molecular cross-section, which in turn is a measure of a molecule's conformation. The gold standard for determining protein conformation is x-ray crystallography, a methodology limited by throughput. There is an unmet need to develop faster ways to measure protein conformation. The proposed technology determines a protein conformation rapidly across all phases of biotherapeutic drug development from discovery, expression system testing, scale up and manufacturing. Additionally, the patented design for this ion mobility spectrometer provides a way to measure changes in conformation that might result as a consequence of exposure to thermal, chemical, and photo-induced stress as needed for drug stability and developability testing. The proposed work will quantify resolution, reproducibility, accuracy, and throughput for this benchtop instrument. The evaluation will be performed using antigen-antibody pairs and several biotherapeutic drugs in collaboration with an academic group and industry partners.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.
