Gonadotrophins--filled-by-mass versus filled-by-bioassay

Application of recombinant technology to FSH in the early 1990s produced a highly purified preparation. Calibration of the product was dependent on the rat 'bioassay' based on measurement of ovarian weight after injection of FSH into rats. This test is associated with variability in the measurement of FSH bioactivity (10-20%) and in the batch-to-batch FSH content. To improve calibration of the final product, a new concept of measuring the final product by mass was developed for follitropin alfa, which has a very consistent isoform profile and a high specific activity. The new formulation of follitropin alfa (FbM) displays a very low batch-to-batch variability (< 2%). The advantages of the FbM formulation have been assessed in clinical practice. A significant improvement in the consistency of the ovarian response reported in IVF cycles is likely to be related to the more precise dosing of FbM batches. Similarly, in patients treated for ovulation induction, the cycle cancellation rate was significantly reduced, as well as the need for dose adjustment and repetitive monitoring. Furthermore, the duration of treatment and the total dose of FSH required for cycles with and without IVF were significantly reduced. In conclusion, the new filled-by-mass formulation of follitropin alfa, by providing a more precise dosing of the FSH content in each batch, markedly improves the convenience and effectiveness of stimulation cycles.