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

SBIR第一阶段提案的目的是扩大QATCH的粘度测量范围 创新的nanovisQTM技术，用于蛋白质基聚合物的精确可注射性和可制造性筛选 治疗学这一目标的动机是不断增长的蛋白质为基础的生物制药的需求 治疗行业（全球市场规模超过800亿美元）。基于蛋白质的治疗剂作为 由于皮下注射的体积限制，高浓度制剂。然而，增加 在这些高浓度下的蛋白质-蛋白质相互作用可引起可注射性和可制造性问题， 由于高样品体积要求，在药物开发的早期阶段不能确定 传统的流变学技术。通过开发宽剪切速率范围、低体积粘度计， 分子可以针对可注射性/可制造性进行优化， 被选中进行升级。该提议是重要的，因为所提出的装置可以评估药物的可注射性。 蛋白质制剂在药物开发中比现有技术更早，因此减少了药物开发的时间， 研发成本花费在开发新的，可注射的蛋白质为基础的治疗相当。在初步研究中， nanovisQTM是一种具有声学传感功能的微流体毛细管粘度计，已成功应用于 在2分钟内使用小于10微升同时测量低剪切速率和非常高剪切速率下的粘度。 QATCH建议：1）通过提高时间分辨率来扩大nanovisQTM的低剪切速率范围， 最小可检测的流动长度，2）通过开发增加高剪切速率的可检测粘度范围 后处理算法，以及3）比较通过nanovisQTM结果计算的注射力和注射力 测量.随着剪切速率和粘度范围的扩大，nanovisQTM应该能够识别关键的 剪切速率、幂律系数以及基于蛋白质的治疗剂的高和低平台粘度。

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 R&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.