Research Project
9134008
? DESCRIPTION (provided by applicant): 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. The presence of such aggregates can mean the discontinuation of potentially critical therapeutic products. The FDA has 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 the technology does not currently exist to accomplish this goal, particularly in the critical range from 100 nm to 10 microns. Protein aggregation occurs at almost every stage in the biopharmaceutical pipeline, from development, formulation, and manufacturing to storage and point of use. Thus, there is a pressing and as-yet unmet need for instrumentation that can assess the size distribution and morphology of protein aggregates in this size range. This SBIR Phase I program will meet this need by developing an instrument, using holographic video microscopy to detect and characterize protein aggregates in pharmaceutical formulations. This transformative technology, originally invented to characterize the properties of spherical colloids and emulsion droplets, can measure single clusters rapidly enough to be used for in-line characterization of pharmaceutical samples, and offers unprecedented and independently verified precision and accuracy. The proposed work will modify existing patented instrumentation and software for application to the measurement of protein aggregates in model systems, will verify the instrument's ability to distinguish protein clusters from industrially relevant contaminants, and will demonstrate the ability to monitor protein-clustering behavior under conditions that enhance or inhibit aggregation. Holographic characterization of protein aggregation will provide the detailed data needed for product development, process control and quality assurance in the biopharmaceutical industry and will result in increased efficiency, safety and cost savings in the promising and rapidly growing area of protein-based therapeutics.
