Batch-to-batch consistency of human-derived gonadotrophin preparations compared with recombinant preparations

Abstract

Different gonadotrophin preparations derived from human urine or manufactured by recombinant technology are currently used in clinical practice for the treatment of infertility. It has been widely assumed that gonadotrophin products manufactured by recombinant technology have better batch-to-batch consistency compared with human-derived preparations and that this potentially will be shown to provide a more constant clinical response, but there is little evidence for either statement. This study compared the batch-to-batch consistency between urinary-derived and recombinant manufactured gonadotrophin preparations using standard analytical techniques, as well as a novel in-vitro follicle bioassay to evaluate the consistency of the biological response at the target organ. Oligosaccharide isoform profiling, immunoassay testing, size exclusion chromatography analysis and in-vitro bioassay testing of urinary derived gonadotrophin preparations (MENOPUR and BRAVELLE) confirm that these products display a high degree of batch-to-batch consistency, similar to recombinant FSH (GONAL-f) either filled by mass or bioassay. The data also suggest that the batch-to-batch variation is independent of the manufacturing procedure (filled-by-bioassay or filled-by-mass) for the recombinant preparation (Gonal-f), but that the total FSH bioactivity delivered from a single dose preparation after reconstitution differs between the two manufacturing procedures.