title: Contribution of animal studies to evaluate the similarity of biosimilars to reference products.
abstract: The European Union (EU) was the first region to establish a regulatory framework for biosimilars, in which animal studies are required to confirm similarity to a reference product. However, animal studies described in European public assessment reports (EPARs) or marketing authorization applications (MAAs) did not identify clinically or toxicologically relevant differences despite differences in quality, suggesting that animal studies lack the sensitivity to confirm biosimilarity. Scientific advice provided learning opportunities to evolve existing guidance. Altogether, the data support a step-wise approach to develop biosimilars that focuses on quality and clinical efficacy of biosimilar. This approach might be more effective and does not necessarily require animal studies, which is also reflected in new EU draft guidance.
authors.affiliation: Utrecht Institute of Pharmaceutical Sciences, Department of pharmaceutics, Utrecht University, Universiteitsweg 99, 3584 CG Utrech, The Netherlands; Medicines Evaluation Board, Graadt van Roggenweg 500, 3531 AH Utrecht, The Netherlands. Electronic address: p.j.k.vanmeer@uu.nl.
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: van Meer
authors.affiliation: Utrecht Institute of Pharmaceutical Sciences, Department of pharmaceutics, Utrecht University, Universiteitsweg 99, 3584 CG Utrech, The Netherlands.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Ebbers
authors.affiliation: Copernicus Institute of Sustainable Development, Innovation studies, Utrecht University, Heidelberglaan 2, 3584 CS Utrecht, The Netherlands.
authors.forename: Marlous
authors.initials: M
authors.lastname: Kooijman
authors.affiliation: Medicines Evaluation Board, Graadt van Roggenweg 500, 3531 AH Utrecht, The Netherlands.
authors.forename: Christine C
authors.initials: CC
authors.lastname: Gispen-de Wied
authors.affiliation: iMED-UL, Department of Pharmacological Sciences, University of Lisbon, Avenida Professor Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Silva-Lima
authors.affiliation: Copernicus Institute of Sustainable Development, Innovation studies, Utrecht University, Heidelberglaan 2, 3584 CS Utrecht, The Netherlands.
authors.forename: Ellen H M
authors.initials: EH
authors.lastname: Moors
authors.affiliation: Utrecht Institute of Pharmaceutical Sciences, Department of pharmaceutics, Utrecht University, Universiteitsweg 99, 3584 CG Utrech, The Netherlands; Copernicus Institute of Sustainable Development, Innovation studies, Utrecht University, Heidelberglaan 2, 3584 CS Utrecht, The Netherlands.
authors.forename: Huub
authors.initials: H
authors.lastname: Schellekens
mesh_terms: D000818:Animals; D059451:Biosimilar Pharmaceuticals / Q000494:pharmacology* / Q000592:standards / Q000633:toxicity; D017277:Drug Approval / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000592:standards; D005062:European Union; D017408:Guidelines as Topic; D006801:Humans; D023421:Models, Animal; D011786:Quality Control; D018570:Risk Assessment; D013045:Species Specificity; D018675:Toxicity Tests
chemical_list: D059451:Biosimilar Pharmaceuticals