Volume 8 Issue 2
Apr.  2018
Turn off MathJax
Article Contents
Robert Karlsson, Veronica Fridh, ?sa Frostell. Surrogate potency assays:Comparison of binding profiles complements dose response curves for unambiguous assessment of relative potencies[J]. Journal of Pharmaceutical Analysis, 2018, 8(2): 138-146.
Citation: Robert Karlsson, Veronica Fridh, ?sa Frostell. Surrogate potency assays:Comparison of binding profiles complements dose response curves for unambiguous assessment of relative potencies[J]. Journal of Pharmaceutical Analysis, 2018, 8(2): 138-146.

Surrogate potency assays:Comparison of binding profiles complements dose response curves for unambiguous assessment of relative potencies

  • Publish Date: Apr. 10, 2018
  • Surface plasmon resonance (SPR) systems are widely used for detailed characterization of antibody ac-tivities including antigen and Fc-receptor binding. During the later stages of development, where the focus is to ensure that established critical quality attributes (CQAs) are maintained during cell culture, purification and formulation processes, analysis is simplified, and relative potencies are often de-termined. Here, simulation of binding data revealed that relative potency values, determined via parallel line analysis (PLA) and half maximal effective concentration (EC50) analysis accurately reflect changes in active concentration only if binding kinetics remain unchanged. Changes in the association rate constant shifted dose response curves, and therefore relative potencies, in the same way as changes in analyte concentration do. However, for interactions characterized by stable binding, changes in the dissociation rate constant did not result in any shift, suggesting that this type of change may go unnoticed in the dose response curve. Thus, EC50 and PLA analyses of dose response curves obtained with an anti-TNF-αan-tibody were complemented with the Biacore functionality for sensorgram comparison analysis, whereby changes in antigen and Fc-receptor binding profiles could be detected. Next, analysis of temperature stressed TNF-α antibody revealed that calibration free concentration analysis (CFCA) data correlated perfectly with relative potency values. Together, these results demonstrate that combinations of SPR based dose response curves, sensorgram comparison and CFCA can be used to strengthen the confidence in relative potency assessments, and suggest that SPR can potentially be used as a surrogate potency assay in the quality control of biotherapeutic medicines.
  • loading
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (95) PDF downloads(0) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return