Reference Protocol to Assess Analytical Performance of Higher Order Structural Analysis Measurements: Results from an Interlaboratory Comparison.
Reference Protocol to Assess Analytical Performance of Higher Order Structural Analysis Measurements: Results from an Interlaboratory Comparison.
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DOI：
10.1021/acs.analchem.0c04625
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发表时间：
2021-07-06
影响因子：
7.4
通讯作者：
Quaglia, M
中科院分区：
文献类型：
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作者：
Groves, K;Ashcroft, A E;Quaglia, M
蛋白质高级结构(HOS)的测量提供了关于生物药物的稳定性、效力、有效性、免疫原性和生物相似性的重要信息，有大量的技术和方法可用于执行这些测量。然而，由于缺乏参考方案和参考测量程序，比较HOS方法的分析性能和结果的标准化并不是一项微不足道的任务。在这里，我们开发了一种方案，对重组生物疗法生长激素的样品进行结构改变和比较，并描述了通过使用一些技术、方法和在不同实验室获得的结果。这样做的最终目的是提供工具和生成数据池，以比较和基准分析平台，并确定对结构变化的方法敏感度。在这项研究中使用的许多方法中，以不同的灵敏度观察到了由于锌浓度增加而引起的生长激素HOS的变化，无论是在全球范围内还是在更局部的分辨率上，这表明该方案适合于提高对平台间和跨平台测量可比性的理解，并适当地评估分析性能。
Measurements of protein higher order structure (HOS) provide important information on stability, potency, efficacy, immunogenicity, and biosimilarity of biopharmaceuticals, with a significant number of techniques and methods available to perform these measurements. The comparison of the analytical performance of HOS methods and the standardization of the results is, however, not a trivial task, due to the lack of reference protocols and reference measurement procedures. Here, we developed a protocol to structurally alter and compare samples of somatropin, a recombinant biotherapeutic, and describe the results obtained by using a number of techniques, methods and in different laboratories. This, with the final aim to provide tools and generate a pool of data to compare and benchmark analytical platforms and define method sensitivity to structural changes. Changes in somatropin HOS, induced by the presence of zinc at increasing concentrations, were observed, both globally and at more localized resolution, across many of the methods utilized in this study and with different sensitivities, suggesting the suitability of the protocol to improve understanding of inter- and cross-platform measurement comparability and assess analytical performance as appropriate.