Injectability analysis of high concentration protein formulations by extending shear-rate range in microfluidic quartz viscometers

The objective of this SBIR Phase I proposal is to expand the viscosity measurement range of QATCH’s innovative nanovisQTM technology for accurate injectability and manufacturability screening of protein-based therapeutics. This objective is motivated by the needs of the growing protein-based biopharmaceutical therapeutics industry (with global market size over $80 billion). Protein-based therapeutics are administered as high concentration formulations due to the volume constraints of subcutaneous injections. However, increased protein-protein interactions at these high concentrations can cause injectability and manufacturability issues, which cannot be determined at early stages of drug development due to the high sample volume requirements of conventional rheology techniques. By developing a wide shear rate range, low volume viscometer, protein molecules can be optimized for injectability/manufacturability and candidates with better developability can be selected for scaling-up. This proposal is significant because the proposed device can assess injectability of protein formulations earlier in drug development than existing technology and consequently reduce the time and cost of Randamp;D spent in developing new, injectable protein-based therapeutics considerably. In preliminary studies, nanovisQTM, which is a microfluidic capillary viscometer with acoustic sensing, has been shown successful in measuring viscosity at low and very high shear-rates simultaneously using less than 10 microliters in 2 minutes. QATCH is proposing to 1) expand the low shear-rate range of nanovisQTM by improving the time-resolution and the minimum detectable flow length, 2) increase the detectable viscosity range of high shear-rates by developing a post-processing algorithm, and 3) compare injection forces calculated by nanovisQTM results and injection force measurements. With the expanded shear-rate and viscosity range, nanovisQTM should be able to identify critical shear-rates, power-law coefficients, and high and low plateau viscosities of protein-based therapeutics.Subcutaneous injections of protein-based therapeutics enable home administration and reduce healthcare costs. However, the injectability of protein-based formulations at the necessary high concentrations for injection cannot be determined at early stages of drug development due to a lack of material. Thus, protein molecules cannot be optimized or selected for injectability. Our technology addresses this by allowing the measurement of viscosity at shear-rate ranges relevant to injectability and manufacturability using very small volumes of formulations. This technology will enable prescreening and optimizing proteins for injectability during early stages of drug development and reduce the risk of scaling, and the associated costs, of uninjectable proteins. In the long-term, the availability of this technology is expected to increase the number of injectable protein-based therapeutics to address patients needs.