Department of Therapeutic Discovery, One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
Biosimilar Business Unit, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
Anal Biochem. 2022 Oct 1;654:114804. doi: 10.1016/j.ab.2022.114804. Epub 2022 Jul 14.
Surface plasmon resonance (SPR) analysis provides important binding characteristic information for an antibody to its binding partner, such as binding specificity and affinity (K). In recent years, SPR has been increasingly used in biosimilar development as part of the comparative analytical similarity assessment. Although there is no systematic study describing how to qualify SPR assays, there are various SPR result types (outputs) that have been used for assay qualification in publicly available regulatory documents. The mixed usage of SPR output can cause confusion and can be misleading when comparing binding attributes among antibody molecules. In this report, using a recombinant huIgG1 (mAb 1) antibody as an example, we performed assay qualification strictly based on the nature of the biomolecular interaction. We recommend that K should be used as the output of assay qualification when the K can be measured accurately by SPR. When K cannot be accurately determined in a SPR setting, sensorgram comparison and Parallel Line Analysis (PLA) can be used to qualify the assay. We emphasize the importance of setting up appropriate SPR assay conditions for target and/or Fc receptor interactions to ensure the assay qualification parameters, such as accuracy and repeatability, to meet the criteria acceptable for regulatory filings. With increasing numbers of biotherapeutics being developed, the methods and guidelines provided here can help to align SPR application between the drug development industry and regulatory authorities which will benefit the scientific communities involved in biotherapeutic drug development.
表面等离子体共振（SPR）分析为抗体与其结合配偶体的结合特性提供了重要信息，例如结合特异性和亲和力（K）。近年来，SPR 已越来越多地用于生物类似药的开发，作为比较分析相似性评估的一部分。尽管没有系统的研究描述如何对 SPR 分析进行验证，但在公开的监管文件中，已经使用了各种 SPR 结果类型（输出）来进行分析验证。SPR 输出的混合使用可能会造成混淆，并且在比较抗体分子之间的结合属性时可能会产生误导。在本报告中，我们使用重组 huIgG1（mAb 1）抗体作为示例，严格基于生物分子相互作用的性质进行分析验证。我们建议，当 SPR 可以准确测量 K 时，应将 K 用作分析验证的输出。当在 SPR 环境中无法准确确定 K 时，可以使用传感器图比较和平行线分析（PLA）来验证分析。我们强调为目标和/或 Fc 受体相互作用设置适当的 SPR 分析条件的重要性，以确保分析验证参数（如准确性和重复性）符合监管备案可接受的标准。随着越来越多的治疗性生物药物的开发，这里提供的方法和指南可以帮助药物开发行业和监管机构之间协调 SPR 的应用，这将使参与治疗性生物药物开发的科学界受益。
