Comparative Assessment of the Structural Features of Originator Recombinant Human Follitropin Alfa Versus Recombinant Human Follitropin Alfa Biosimilar Preparations Approved in Non-European Regions

Abstract

Although the full primary structures of the alfa and beta subunits of reference r-hFSH-alfa and its biosimilars are identical, cell context-dependent differences in the expressing cell lines and manufacturing process can lead to variations in glycosylation profiles. In the present study, we compared the structural features of reference r-hFSH-alfa with those of five biosimilar preparations approved in different global regions outside Europe (Primapur®, Jin Sai Heng®, Follitrope®, Folisurge®, and Corneumon®) with respect to glycosylation, macro- and microheterogeneity, and other post-translational modifications and higher order structure. The mean proportion of N-glycosylation-site occupancy was highest in reference r-hFSH-alfa, decreasing sequentially in Primapur, Jin Sai Heng, Corneumon, Follisurge and Follitrope, respectively. The level of antennarity showed slightly higher complexity in Corneumon, Primapur and Follitrope versus reference r-hFSH-alfa, whereas Jin Sai Heng and Folisurge were aligned with reference r-hFSH-alfa across all N-glycosylation sites. Sialylation level was higher in Corneumon and Follitrope, but small differences were detected in other biosimilar preparations compared with reference r-hFSH-alfa. Jin Sai Heng showed higher levels of N-glyconeuramic acid than the other preparations. Minor differences in oxidation levels were seen among the different products. Therefore, in summary, we identified var ious differences in N-glycosylation occupancy, antennarity, sialylation and oxidation between reference r-hFSH-alfa and the biosimilar preparations analyzed.

Comparative assessment of the DNA damage caused in cumulus cells by Corneumon®, Gonal-F®, Pergoveris® and Puregon® in women undergoing assisted reproduction techniques, and its impact on reproductive outcomes

“…After the rst rhFSH-α preparation (Gonal-F®) was produced using recombinant DNA technology, several rhFSH have been approved by the corresponding authorities for multifollicular development in women undergoing ART, an even when the full primary structures of the different rhFSH are identical, differences in the expressing cell lines and manufacturing process can lead to variations in glycosylation pro les that could lead to variations in the e cacy among the various rhFSH [13]. For this reason, several studies have been undertaken to evaluate the effectiveness and safety of different rhFSH in inducing COH in infertile women [17][18][19][20][21].…”

“…FSH preparations derived from a urinary source have been successfully used in women undergoing COH for ART, but recently several human recombinant follicle stimulating hormones (rhFSH) have become available [11,12]. Despite the identical amino acid sequences of the different rhFSH, various differences in N-glycosylation occupancy, sialylation, antennarity and oxidation have been reported between them, which in uence the isoform pro les of the rhFSH [13] The aim of the present study was to carry out a comparative assessment of the DNA damage caused in CCs by four rhFSH widely used in COH for IVF protocols, Corneumon®, Gonal-F®, Pergoveris® and Puregon® in women undergoing ART, and to analyze the impact of the CCs DNA damage on several reproductive outcomes.…”