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.
