Gyrolab™xP是用于进行配体结合测定(LBA)的微流体平台,并因其在发现生物分析中的实用性而得到认可。然而,很少有报道关注受管制的生物分析技术。该技术具有试剂消耗少的优点,低样品体积,和自动化配体结合方法。为了改善生物分析测试时间表,并提高向患者提供生物治疗药物的速度,我们评估了该技术在减少检测时间内提供高质量数据的潜力,用于调节生物分析.验证了六种LBA方法,以支持GLP毒代动力学或临床药代动力学研究的生物分析。验证,样本分析,和方法转移进行了描述。总的来说,大约4000个样本已被测试用于调节生物分析,以支持6个GLP毒理学研究,大约1000个样本支持2个临床研究.Gyrolab™xP具有高的运行合格率(≥83%)和高的招致样品再分析(ISR)合格率(>94%)。对于所有六个LBA,在给定测定的所有QC水平上观察到的最大总误差<30%。在光盘(CD)中观察到高仪器响应精度(CV≤5%),和方法被验证为在Gyrolab™xP运行中使用跨多个CD的单个标准曲线。与标准手动基于平板的方法相比,生物分析时间缩短,和方法被成功地转移到测试实验室,为该平台用于后期临床开发铺平了道路。
The Gyrolab™ xP is a microfluidic platform for conducting ligand binding assays (LBAs) and is recognized for its utility in discovery bioanalysis. However, few
reports have focused on the technology for regulated bioanalysis. This technology has the advantage of low reagent consumption, low sample volume, and automated ligand binding methods. To improve bioanalysis testing timelines and increase the speed at which biotherapeutics are delivered to patients, we evaluated the technology for its potential to deliver high-quality data at reduced testing timelines for regulated bioanalysis. Six LBA methods were validated to support bioanalysis for GLP toxicokinetic or clinical pharmacokinetic studies. Validation, sample analysis, and method transfer are described. In total, approximately 4000 samples have been tested for regulated bioanalysis to support 6 GLP toxicology studies and approximately 1000 samples to support 2 clinical studies. Gyrolab™ xP had high run pass rates (≥83%) and high incurred sample reanalysis (ISR) pass rates (>94%). The maximum total error observed across all QC levels for a given assay was <30% for all six LBAs. High instrument response precision (CV ≤5%) was observed across compact discs (CDs), and methods were validated to use a single standard curve across multiple CDs within a Gyrolab™ xP run. Reduced bioanalysis timelines were achieved compared to standard manual plate-based methods, and methods were successfully transferred across testing labs, paving the way for this platform for use in late-stage clinical development.