Better bioassays via designs for robots analyses with improved model selection and similarity bounds that limit potency bias

通过机器人分析设计实现更好的生物测定，并改进模型选择和限制效力偏差的相似性界限

• 批准号: 10155988
• 负责人: David Matthew Lansky
• 金额: $ 25.2万
• 依托单位: PRECISION BIOASSAY, INC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10155988
• 关键词: Address; Area; Biological; Biological Assay; Biological Products; Biological Response Modifier Therapy; Biotechnology; Cell Therapy; Collection; Complex; Computer software; Consult; Data; Development; Ensure; Failure; Generations; Goals; Knowledge; Laboratories; Lead; Manufacturer Name; Measurement; Measures; Medical; Methods; Modeling; Modernization; Monitor; Non-linear Models; Organism; Output; Performance; Pharmaceutical Preparations; Phase; Process; Production; Proteins; Quality Control; Random Allocation; Randomized; Research; Risk; Robot; Robotics; Sampling; Services; Small Business Innovation Research Grant; Source; Specific qualifier value; Statistical Methods; Structure; Technology; Testing; Vaccines; Variant; base; commercial application; consumer product; cost; design; experience; gene therapy; improved; manufacturing process; novel; novel strategies; product development; prototype; software as a service; statistical service; therapeutic protein; tool

Project Summary Biological assays (bioassays) provide critical measurements of the activity of complex biological drug products (proteins, vaccines, cell therapy, and gene therapy products) particularly during product development and production quality control. These assays use living systems for measurement and have special designs and analyses to accommodate the large variation and confounding factors involved. Common lab bioassays impose complex statistical structures that, if not designed and analyzed properly, lead to poor precision for estimates of potency and limited capabilities to monitor assays for developing problems. These problems contribute to lot release failures for manufacturers and slow down or block the development of biopharmaceutical products for consumers. Precision Bioassay provides statistical services for bioassays, helping organizations that develop, use, perform, validate, monitor, and regulate bioassays use modern methods to get better information and performance, ultimately improving the quality and accelerating the discovery of biopharmaceutical drug products. The proposed research will lead to three new tools that will improve bioassay design, analyses and monitoring, each will become a new product (a combination of software and consulting support). New bioassay designs that exploit the capabilities of modern robots will, in combination with good analyses, separate important sources of variation that are confounded with current designs and analyses; this improved information will accelerate bioassay development and enhance monitoring of bioassays. Improved methods for selection of which sources of variation to include in bioassay analysis models (equivalence-based random effects model selection) will improve estimation of important sources of variation that are often ignored with current analysis methods; this will substantially improve bioassay monitoring. Limiting bias of potency is essential to ensuring that a bioassay is fit for its intended use: a new approach to setting bounds for equivalence tests of similarity of test samples to standards will limit bias of potency associated with allowed non-similarity to pre-specified levels, ensure that most samples that are similar will pass similarity, and estimate the assay size required to achieve this performance target. In Phase II we will extend the proof-of-concept results from this research using prototype software able to address practical cases. The products from this research will become additional packages in our existing software and consulting services that will accelerate the development of biopharmaceutical products.

项目概要 生物测定（生物测定）提供复杂生物药品活性的关键测量 （蛋白质、疫苗、细胞治疗和基因治疗产品）特别是在产品开发和 生产质量控制。这些测定使用生命系统进行测量，并具有特殊的设计和 分析以适应所涉及的巨大变化和混杂因素。常见的实验室生物测定 强加复杂的统计结构，如果设计和分析不当，会导致精度较差 监测检测方法以发现问题的效力和有限能力的估计。这些问题 导致制造商批次放行失败，并减慢或阻碍开发 面向消费者的生物制药产品。 Precision Bioassay 为生物测定提供统计服务，帮助组织开发、使用、 执行、验证、监控和监管生物测定，使用现代方法来获取更好的信息和 性能，最终提高质量并加速生物制药药物的发现 产品。拟议的研究将产生三种新工具，这些工具将改进生物测定设计、分析和 监控，每一个都将成为一个新产品（软件和咨询支持的组合）。新生物测定法 利用现代机器人能力的设计将结合良好的分析，将 与当前设计和分析相混淆的重要变异来源；这改善了 信息将加速生物测定的发展并加强对生物测定的监测。改进方法 选择将哪些变异来源纳入生物测定分析模型（基于等效性的随机 效应模型选择）将改善对重要变异源的估计，而这些变异源经常被忽视 当前的分析方法；这将大大改善生物测定监测。效力的限制偏差是 确保生物测定适合其预期用途至关重要：设定界限的新方法 测试样品与标准相似性的等效性测试将限制与允许的效力相关的偏差 与预先指定的水平不相似，确保大多数相似的样本将通过相似性，并且 估计实现该性能目标所需的检测规模。 在第二阶段，我们将使用原型软件扩展这项研究的概念验证结果，该软件能够 解决实际案例。这项研究的产品将成为我们现有的附加包 软件和咨询服务将加速生物制药产品的开发。