High-throughput injectability screening of high concentration protein formulations by microfluidic quartz resonators

通过微流控石英谐振器对高浓度蛋白质制剂进行高通量可注射性筛选

• 批准号: 10760592
• 负责人: Zehra Parlak
• 金额: $ 95.12万
• 依托单位: QATCH TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2025-09-14
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10760592
• 关键词: Acoustics; Address; Antibody Therapy; Behavior; Biological Assay; Biological Products; Blood capillaries; Chronic; Computer software; Consumption; Custom; Data; Development; Devices; Disease Management; Drops; Drug Formulations; Electronics; FDA approved; Failure; Formulation; Health Care Costs; Health care facility; Home; Industry; Infusion procedures; Injectable; Injections; Intravenous infusion procedures; Investments; Marketing; Measurement; Measures; Microfluidics; Nature; Patient Preferences; Patients; Persons; Phase; Positioning Attribute; Proteins; Quartz; Resolution; Rheology; Risk; Risk Reduction; Sampling; Small Business Innovation Research Grant; Solubility; Subcutaneous Injections; System; Technology; Temperature; Testing; Therapeutic; Time; Viral Vector; Viscosity; commercialization; cost; drug development; injection/infusion; instrument; manufacturability; manufacture; manufacturing process; milliliter; preclinical development; prevent; protein protein interaction; prototype; research and development; scale up; screening; sensor; small molecule; temporal measurement

The objective of this SBIR Direct Phase II proposal is to carry QATCH’s nanovisQ™ technology, which is a wide-shear-rate range and low volume viscometer for determining developability and injectability of biopharmaceutical formulations, from single-test sensors to high-throughput and automated format. This objective is motivated by the needs of the growing protein-based biopharmaceutical therapeutics industry (with global market size over $300 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 high viscosity and prevent injectability and manufacturability. Existing viscometers consume high volumes of sample, which prevents early-stage assessment and still have high protein and time costs at later stages. By developing a high-throughput, automated, wide shear rate range, low volume viscometer, protein molecules and formulations can be optimized for injectability/manufacturability earlier with less cost and risk. This proposal is significant because the proposed device can start assessing injectability of protein formulations earlier in drug development, perform this test in a higher number of formulations faster and with less material than existing technologies and consequently reduce the time and cost of R&D spent in developing new, injectable protein-based therapeutics considerably. As preliminary studies, QATCH demonstrated wide-shear-rate and low sample volume viscometers for protein formulations in single- test format. In addition, QATCH showed that 4 simultaneous measurements from 4 sensors with 9 mm spacing on the same quartz blank can be achieved accurately. As a result, the nanovisQ™ is now positioned to be a 6x4 sensor matrix and automated viscometer for high concentration protein formulations. In SBIR Phase II QATCH is proposing to 1) develop 4-sensor arrays with extended shear-rate viscosity measurements to serve high- concentration protein formulations 2) develop 6x4 sensor matrix for the high-throughput system with environmental control and the automated sample delivery capability. Developing a high-throughput and automated low-sample volume viscometer is a key step towards commercialization since low-sample volume and high-throughput are two most important parameters for drug development groups.

该SBIR直接II期建议的目的是携带Qatch的Nanovisq™技术，这是一个 宽剪切率范围和低容量粘度计，用于确定开发和注射性 从单测传感器到高通量和自动化格式的生物制药公式。这 目标是由成长基于蛋白质的生物药物治疗行业的需求激励的（与 全球市场规模超过3000亿美元）。基于蛋白质的治疗剂是作为高浓度的 由于皮下注射的体积限制而引起的公式。但是，蛋白质蛋白质增加 在这些高浓度下的相互作用会导致高粘度，并防止注射性和制造性。 现有的粘度计消耗大量样本，这可以防止早期评估，并且仍然具有 较高的蛋白质和时间成本在以后的阶段。通过开发高通量，自动化，宽的剪切速率范围， 低容量的粘蛋白，蛋白质分子和配方可以优化用于注射性/生产性 较早的成本和风险。该提议很重要，因为拟议的设备可以开始评估 在药物开发中较早的蛋白质配方的注射性，以较高数量的 公式比现有技术更快，材料少，因此降低了时间和成本 研发在开发新的，可注射蛋白质的疗法方面的支出。作为初步研究， QATCH显示了单个蛋白配方蛋白配方蛋白公式的宽剪切率和低样品体积粘度表 测试格式。此外，Qatch显示了4个带有9 mm间距的4个传感器的简单测量 可以准确地实现同一石英空白。结果，Nanovisq™现在位于6x4 高浓度蛋白配方的传感器基质和自动粘度计。在SBIR II期 提议1）开发具有延长的剪切粘度测量值的4传感器阵列，以服务高 浓度蛋白配方2）用高通量系统开发6x4传感器矩阵 环境控制和自动样品输送能力。开发高通量和 自动化的低样本卷粘仪是迈向商业化的关键步骤，因为低样本体积 高通量是药物开发组的两个最重要参数。