Characterization of Colloidal Plasma Volume Expanders

摘要：在截至2001年9月30日的报告年度内，CBER没有就该项目开展任何工作。然而，在2000年期间，作为羟乙基淀粉原料药生产新方法验证的一部分，Fresenius Kabi Austria（FKA）测定了CBER提供的6批羟乙基淀粉和4份创新羟乙基淀粉样品的各种重均和数均分子量（分别为Mw和Mn）值。FKA采用非商业化、复杂的SE-HPLC方法，该方法需要唯一的校准标准品，并已通过CBER验证。尽管如此，所得数据现在提供了一种评估Wyatt Technology，Corp.的商业MALLS-SE-HPLC方法准确测定级分GTE 50，000的羟乙基淀粉Mn值的能力的方法，该值可能与效价更相关由于分子量LT 50，000的分子从脉管系统中快速清除，因此整体的Mn（或整体的Mw）比整体的Mn（即，体内粘附潜力）高。我们注意到，Wyatt Technology的MALLS-SE-HPLC方法允许测定相对准确的整体Mw值（目前用于监管目的），但由于SE-HPLC分布中较低分子量物质的散射效率相对较低，因此不允许准确测定整体Mn。 如果2002财年期间时间允许，我们将要求Wyatt Technology Corp.通过MALLS-SE-HPLC测定上述4个CBER样品以及上述6批FKA羟乙基淀粉（如果我们能够获得这些FKA材料的样品，其值已在上文报告）的全部和馏分GTE 50，000的Mw和Mn值。

Summary: During the reporting year ending September 30, 2001, no work was performed on this project at CBER. However, during the year 2000, as part of the validation of a new method of manufacturing Hetastarch drug substance, Fresenius Kabi Austria (FKA) determined various weight average and number average molecular weight (Mw and Mn, respectively) values for 6 lots of their Hetastarch and 4 samples of innovator Hetastarch, supplied by CBER. FKA utilizes a non-commercial, complicated SE-HPLC method that requires a unique standard for calibration and that has been validated by CBER. Nevertheless, the resultant data now provide a way of assessing the ability of the commercial MALLS-SE-HPLC method of Wyatt Technology, Corp. to accurately determine values for Hetastarch of Mn of the Fraction GTE 50,000, a value probably more related to potency (i.e. in vivo oncotic potential) than Mn of the Whole (or Mw of the Whole) since molecules of molecular weight LT 50,000 are rapidly cleared from the vasculature. We note that the MALLS-SE-HPLC methodology of Wyatt Technology allows the determination of relatively accurate values of Mw of the Whole (currently used for regulatory purposes) but does not permit accurate determination of Mn of the Whole due to the relatively low scattering efficiency of the lower molecular weight species in the SE-HPLC distribution. If time permits during FY 2002, we will request that Wyatt Technology Corp. determine by MALLS-SE-HPLC the Mw and Mn values of the Whole and Mn of the Fraction GTE 50,000 of the 4 CBER samples referenced above in addition to the 6 lots of FKA Hetastarch for which values are reported above if we can procure samples of these FKA materials.