Quantification of Follicle Stimulating Hormone (follitropin alfa): Is In Vivo Bioassay Still Relevant in the Recombinant Age?

R. Driebergen, G. Baer


Curr Med Res Opin. 2003;19(1) 

In This Article

Alternative Physico-Chemical Methodology

Size exclusion high performance liquid chromatography (SE-HPLC) represents an alternative physico-chemical method by which Serono - the manufacturers of Gonal-F* (r-hFSH, follitropin-alfa) - are now able to quantify r-hFSH protein in both drug substance and final product with high reliability. This technique has far greater precision than the Steelman-Pohley in vivo bioassay (%CV 1-2% vs %CV 10%) and supports an intended 'target mass' ± 10% specification range. This represents a significant improvement in product quality and batch-to-batch consistency compared with the current protein content range of ± 23% for Gonal-F 75 IU vials/ampoules, filled by IU and released by bioassay against the 80-125% biopotency specification. The SE-HPLC method used is very robust and provides highly consistent analytical results at multiple laboratories, as shown in Table 1 . However, this optimised SE-HPLC method is only viable because:

  • The drug substance manufacturing process produces r-hFSH protein with a consistent physico-chemical quality

  • The compounding, filling and finishing process maintains the integrity of the r-hFSH molecule, ensuring consistent biological quality

  • A reliable conversion factor has been determined to calculate the equivalent of IU in µg.

*Gonal-F is a registered trade name of Serono S.A., Switzerland


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.