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

项目摘要 生物分析提供复杂生物药物产品活性的关键测量。 (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 产品质量控制。这些分析使用生命系统进行测量，并有特殊的设计和 分析以适应所涉及的较大差异和混杂因素。常见的实验室生物检测方法 强加复杂的统计结构，如果设计和分析不当，将导致 对效力的估计和对正在发展的问题的检测的有限的能力。这些问题 导致制造商的批次放行失败，并减缓或阻碍 面向消费者的生物制药产品。 精密生物检测为生物检测提供统计服务，帮助组织开发、使用、 使用现代方法执行、验证、监测和规范生物检测，以获得更好的信息和 性能，最终提高质量，加速生物制药的发现 产品。这项拟议的研究将产生三种新工具，它们将改进生物检测设计、分析和 监测，每个都将成为一个新的产品(软件和咨询支持的组合)。新的生物测定法 利用现代机器人能力的设计，与良好的分析相结合，将分开 与当前设计和分析相混淆的重要变化来源；这一改进 信息将加快生物检测的发展，并加强对生物检测的监测。改进的方法，用于 选择将哪些变异源纳入生物测定分析模型(基于等价性的随机 影响模型选择)将改进对经常被忽略的重要变异源的估计 目前的分析方法；这将大大改善生物检测监测。限制效力的偏差是 确保生物化验适合其预期用途的关键：一种设定界限的新方法 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 不相似性到预先指定的水平，确保大多数相似的样本将通过相似性，以及 估计实现这一性能目标所需的化验大小。 在第二阶段，我们将使用原型软件扩展此研究的概念验证结果 解决实际案例。这项研究的产品将成为我们现有产品的附加包装 将加快生物制药产品开发的软件和咨询服务。

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.