High Precision Bioassay Using Robotics and Statistics

描述（由申请人提供）：摘要即使经过大量的开发努力，细胞培养生物测定通常也是费力和不精确的。这些生物测定法在生物技术工业中广泛用于测量开发中的蛋白质或疫苗产品和批量放行。不精确的检测和缓慢的检测开发导致产品开发缓慢。细胞培养生物测定的常见做法忽略了统计和监管指导，没有利用适当的随机化，也没有考虑群体效应（即，由多通道移液器引起的）。此外，缺乏对分析中的位置效应的关注，再加上对分析数据的简单分析，损害了细胞培养生物分析的准确性和效率。Lansky咨询有限责任公司将开发一种标准化的方法，使用实验室机器人进行细胞培养生物测定，然后进行现代统计分析。这一组合将解决随机化、定位效应、连续稀释、分组稀释和分析反应的多种变异源的需求。本提案中描述的工作将展示与以下方面相关的性能收益：1)标准化设计（包括需要机器人进行随机化的设计），2)用于生物测定分析的线性和非线性混合分割或条形图模型，以及3)实现这种现代标准化生物测定方法的进展。从现代生物测定方法的组合包的精度增益将显示减少需要一个数量级或更多的样品复制。模拟数据和生物分析的长期实验室实验都将被使用。这些新方法的优点包括降低分析成本，快速应用于新的分析系统，以及易于获得设计、实施和分析的最佳实践。最重要的是，通过建立一个交钥匙机器人和分析生物测定系统，这种水平的测定性能将广泛地提供给生物技术行业以及非营利研究人员。生物测定是药物蛋白和疫苗产品开发和批量放行的关键测量系统。方便地获得高效的生物测定方法将使生物技术产品的开发更快、更明智。改进的生物测定技术将把独特的、重要的蛋白质和疫苗产品更快地推向市场，以满足迫切的医疗需求。

DESCRIPTION (provided by applicant): Abstract Cell culture bioassays are often laborious and imprecise even after substantial development efforts. These bioassays are used broadly in the biotechnology industry to measure protein or vaccine products in development and for lot release. Imprecise assays and slow assay development contribute to slow product development. Common practice in cell culture bioassay ignores statistical and regulatory guidance by failing to utilize proper randomization and not accounting for group effects (i.e.; as caused by multi-channel pipettes). In addition, lack of attention to location effects within the assays, combined with simplistic analyses of assay data, compromise the precision and efficiency of cell culture bioassays. Lansky Consulting LLC will develop a standardized approach to cell culture bioassay using laboratory robots followed by modern statistical analysis. This combination will address the need for randomization, location effects, serial dilution, grouped dilution, and multiple sources of variation in assay response. The work described in this proposal will demonstrate the performance gains associated with: 1) standardized designs (including designs that require robots for randomization), 2) linear and nonlinear mixed split- or strip-plot models for bioassay analysis, and 3) advances in implementation of this modern standardized approach to bioassays. The precision gains from the combined package of modern bioassay methods will be shown to reduce the need for sample replication by an order of magnitude or more. Both simulated data and long-term lab experiments with bioassays will be used. The benefits of these new methods include lower assay costs, rapid application to new assay systems, and easy access to best practices in design, implementation, and analysis. Most importantly, by building a turnkey robotic and analysis bioassay system, this level of assay performance will be made broadly available to the biotechnology industry as well as to non-profit researchers. Project Summary Narrative Bioassays are critical measurement systems for both development and lot release of pharmaceutical protein and vaccine products. Easy access to high performance bioassays will enable faster and better informed development of biotechnology products. Improved bioassay technology will bring unique, important protein and vaccine products to market more quickly to address pressing medical needs.