title: Manufacturing of Recombinant Human Follicle-Stimulating Hormone Ovaleap®(XM17), Comparability with Gonal-f®, and Performance/Consistency.
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.
authors.affiliation: Teva Biotech GmbH, Member of the Teva Group, Dornierstrasse 10, 89079, Ulm, Germany. rainer.winstel@ratiopharm.de.
authors.forename: Rainer
authors.initials: R
authors.lastname: Winstel
authors.affiliation: Teva Biotech GmbH, Member of the Teva Group, Dornierstrasse 10, 89079, Ulm, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Wieland
authors.affiliation: Merckle GmbH, Member of the Teva Group, Graf-Arco-Straße 3, 89079, Ulm, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Gertz
authors.affiliation: Merckle GmbH, Member of the Teva Group, Graf-Arco-Straße 3, 89079, Ulm, Germany.
authors.forename: Arnd
authors.initials: A
authors.lastname: Mueller
authors.affiliation: Teva Biotech GmbH, Member of the Teva Group, Dornierstrasse 10, 89079, Ulm, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Allgaier
mesh_terms: D059451:Biosimilar Pharmaceuticals / Q000737:chemistry*; D005640:Follicle Stimulating Hormone / Q000737:chemistry*; D043373:Follicle Stimulating Hormone, Human / Q000737:chemistry*; D006801:Humans; D010062:Ovulation Induction / Q000379:methods; D011994:Recombinant Proteins / Q000737:chemistry*
chemical_list: D059451:Biosimilar Pharmaceuticals; D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; C571801:follitropin alfa; D005640:Follicle Stimulating Hormone