Manufacturing of Recombinant Human Follicle-Stimulating Hormone Ovaleap? (XM17), Comparability with Gonal-f?, and Performance/Consistency

摘要

Ovaleap? (XM17) is a recombinant human follicle-stimulating hormone to treat infertility by inducing ovulation or controlled ovarian stimulation for assisted reproductive technology (ART) procedures. Ovaleap? (follitropin-α) was approved by the European Medicines Agency in 2013 as a biosimilar medicinal product to the reference medicine, Gonal-f?. Information is often not easily accessible and/or publicly available regarding the rigorous manufacturing procedures for biosimilars. Objectives of the current analysis were to report on validation procedures for the Ovaleap? manufacturing process, to compare the characteristics of Ovaleap? versus Gonal-f?, and to describe the performance and consistency of Ovaleap?. Formal validation of the Ovaleap? manufacturing process was performed at full commercial scale, consisting of several consecutive fermentation and purification runs. Comparison with Gonal-f? involved numerous techniques to determine molecular structure, isoform distribution, biological activity, and product-related impurities. The stability of the multidose application system, targeted for long-term stability at ambient temperature, was assessed and demonstrated. All analyses showed the manufacturing process of Ovaleap? to be robust and consistent. Ovaleap? was found to have similar characteristics when compared with Gonal-f?. This analysis supports the role of Ovaleap? as a biosimilar to Gonal-f?, thus providing patients and clinicians with another therapeutic option during ART procedures.