( ! 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 based on holographic video microscopy (HVM) to detect and count protein aggregates rapidly and reliably enough for monitoring pharmaceutical formulations. Results from the Phase II work has resulted in sales of instruments to major pharmaceutical companies and universities. Early adopters and prospective customers have identified key additional capabilities that would enable them to deploy this technique at all stages of their process from formulation development and metrology into quality assessment and manufacturing process control where Spheryx?s technology has the potential to improve product quality and reduce manufacturing costs. This Phase IIB work will extend Spheryx?s capabilities to meet their needs.
The specific aims of this work are: (1) detect and distinguish contaminants currently challenging biologics manufacturing including air bubbles and metal particles; (2) diagnosing handling-induced composition changes including changes caused by shear forces and by viscosity and temperature variation during processing. Both hardware and software innovations will be needed to accomplish these additional capabilities. The results of this work will be a powerful new manufacturing tool with unique capabilities to meeting critical needs for the biologics industry. ! !
The tendency for proteins to aggregate is a critical barrier to developing and manufacturing biopharmaceuticals, largely because there have been no fast, effective and reliable methods to detect and characterize protein aggregates in their native formulations. This SBIR Phase IIB program will extend the breakthrough capabilities for particle analysis developed in the Phase II program to meet expressed customer needs so that Spheryx technology can be deployed in quality control and manufacturing to create safer biologic products. Hardware and software innovations of holographic analysis will be implemented, tested, and confirmed for use in biopharmaceutical manufacturing by simultaneously measuring the concentrations of multiple categories of contaminants in real-world samples, under multiple simulated manufacturing conditions. .
