Characterization of Non-Protein Colloidal Plasma Volume

摘要：在截至2002年9月30日的报告年度中，CBER没有对该项目进行任何工作。然而，在2000年期间，作为一种新的Hetastarch原料药生产方法验证的一部分，奥地利费森尤斯卡比公司（FKA）测定了由CBER提供的6批Hetastarch和4批创新Hetastarch样品的各种重量平均和数平均分子量（分别为Mw和Mn）值。FKA采用了一种非商业的、复杂的SE-HPLC方法，该方法需要一个独特的校准标准，并已通过CBER验证。然而，所得数据现在提供了一种评估Wyatt Technology， co .的商用MALLS-SE-HPLC方法的能力的方法，可以准确地确定分数GTE 50,000 Mn的Hetastarch值，这个值可能与效价（即体内肿瘤潜能）更相关，而不是整体Mn（或整体Mw），因为分子量lte 50,000的分子会迅速从血管中清除。我们注意到，Wyatt Technology的MALLS-SE-HPLC方法可以相对准确地测定整体的Mw值（目前用于监管目的），但由于SE-HPLC分布中低分子量物质的散射效率相对较低，因此不能准确测定整体的Mn值。如果时间允许，我们将要求Wyatt Technology co .通过MALLS-SE-HPLC测定上述4个CBER样品的Whole和分数GTE 50,000的Mn的Mw和Mn值，以及上述6批FKA Hetastarch的值，如果我们能获得这些FKA材料的样品。

Summary: During the reporting year ending September 30, 2002, 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, 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.