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

重组人促卵泡激素Ovaleap® (XM17)的生产、与Gonal-f®的可比性以及性能/一致性

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Abstract

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.

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