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

通过扩展微流控石英粘度计的剪切速率范围来分析高浓度蛋白质制剂的可注射性

• 批准号: 10080997
• 负责人: Zehra Parlak
• 金额: $ 25万
• 依托单位: QATCH TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080997
• 关键词: Abate; Acoustics; Address; Algorithms; Antibody Therapy; Behavior; Biological Products; Blood capillaries; Data; Development; Devices; Dimensions; Dose; Ensure; FDA approved; Failure; Formulation; Frequencies; Health Care Costs; Height; Home environment; Industry; Injectable; Injections; Intravenous infusion procedures; Investments; Laws; Lead; Length; Liquid substance; Measurement; Measures; Microfluidics; Modulus; Monoclonal Antibodies; Motion; Patient Preferences; Patients; Phase; Positioning Attribute; Problem Solving; Proteins; Quartz; Research; Resolution; Rheology; Risk; Sampling; Side; Small Business Innovation Research Grant; Subcutaneous Injections; Surface; System; Techniques; Technology; Testing; Therapeutic; Thick; Thinness; Time; Viscosity; base; candidate selection; cost; drug development; early screening; improved; innovation; manufacturability; milliliter; preclinical development; protein protein interaction; research and development; scale up; screening; sensor

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.

SBIR I期建议的目的是扩大Qatch的粘度测量范围 创新的NanovisQTM技术，用于精确注射性和基于蛋白质的制造筛查 疗法。该目标是由不断增长的基于蛋白质的生物药物的需求激励的 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被用作 高浓度公式由于皮下注射的体积限制而引起的。但是，增加了 在这些高浓度下的蛋白质 - 蛋白质相互作用会导致注射性和制造问题， 由于样本量的高度要求，无法在药物开发的早期阶段确定 传统的流变技术。通过开发较大的剪切速率范围，低容量粘仪，蛋白质 可以针对注射性/生产性进行优化分子，并且可以更好地发育的候选者 选择进行扩展。该提议很重要，因为提议的设备可以评估 蛋白质在药物开发中的蛋白质配方比现有技术早，从而减少了时间和 研发成本在开发新的，可注射蛋白质的疗法方面的成本相当大。在初步研究中， NanovisqTM是一种具有声感应的微流体毛细管粘膜，在 仅在2分钟内使用少于10微升的低剪切速率测量粘度。 Qatch提议1）通过改善时间分辨率和 最小可检测的流量长度，2）通过开发增加高剪切速率的可检测粘度范围 后处理算法和3）比较通过纳米诺维斯基QTM结果和注射力计算的注射力 测量。随着剪切率和粘度范围的扩大，Nanovisqtm应该能够识别关键 基于蛋白质的治疗的剪切率，幂律合作以及高原粘度。