The very forces critical to creating the three-dimensional structure of proteins are also responsible for unwanted and often dangerous protein aggregates in protein- based therapeutics. Protein aggregation occurs at every stage in the pipeline, from development, formulation, and manufacturing to shipping, storage and point of use. The FDA advised in its 2014 Guidance for Industry that ``It is critical for manufacturers of therapeutic protein products to minimize protein aggregation to the extent possible'', while acknowledging that technology does not currently exist to accomplish this goal, particularly in the critical sub-visible range from 100 nm to 10 microns. Thus, there is a pressing and unmet need for instrumentation that can assess the size distribution and morphology of protein aggregates in this size range. The parent SBIR Phase II program is meeting this need by developing an instrument that uses holographic video microscopy to characterize protein aggregates rapidly and reliably enough for in-line monitoring of pharmaceutical formulations. The Phase II work is harnessing patented capabilities for automated high-throughput measurement of real-world samples. Hardware and software innovations will ensure accuracy and efficacy in high-speed characterization, and to further increase the sophistication and reliability of particle differentiation even when different components are the same size. This program will also elucidate the influence of increased flow speed on protein aggregation. Holographic characterization of protein aggregation will provide detailed data needed for product development, process control and quality assurance in the biologics industry resulting in increased efficiency, safety and cost savings in this rapidly growing field. The diversity candidates will participate in this invention and discovery process providing them with critical training and experience at this important stage in their careers.
The tendency for proteins to aggregate is a critical barrier to developing and manufacturing biopharmaceuticals for targeting a wide array of diseases, largely because there are no fast, effective and reliable methods to detect and characterize these clusters. This proposed SBIR Phase II program will develop an instrument that uses holographic video microscopy to meet this need, resulting in increased efficiency, safety, and cost savings in the promising and rapidly growing area of protein-based therapeutics. The diversity candidates will participate in the modifications of holographic characterization of for use in the biopharmaceutical industry by simultaneously measuring the concentrations of similarly sized different components, including protein aggregates, in real-world samples, with high-throughput microfluidic sample handling.
