title: Biosimilars entering the clinic without animal studies. A paradigm shift in the European Union.
abstract: The concept of biosimilars has spread from Europe to other regions throughout the world, and many regions have drafted regulatory guidelines for their development. Recently, a paradigm shift in regulatory thinking on the non-clinical development of biosimilars has emerged in Europe: In vivo testing should follow a step-wise approach rather than being performed by default. To not require animal testing at all in some instances can well be seen as a revolutionary, but science-based, step. Here, we describe the internal discussions that led to this paradigm shift. The mainstay for the establishment of biosimilarity is the pharmaceutical comparability based on extensive physicochemical and biological characterization. Pharmacodynamic comparability can be evaluated in in vitro assays, whereas pharmacokinetic comparability is best evaluated in clinical studies. It is considered highly unlikely that new safety issues would arise when comparability has been demonstrated based on physicochemical and in vitro comparative studies.
authors.affiliation: a Medicines Evaluation Board (CBG-MEB) ; Utrecht , Netherlands.
authors.forename: Leon A G J M
authors.initials: LA
authors.lastname: van Aerts
authors.forename: Karen
authors.initials: K
authors.lastname: De Smet
authors.forename: Gabriele
authors.initials: G
authors.lastname: Reichmann
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: van der Laan
authors.forename: Christian K
authors.initials: CK
authors.lastname: Schneider
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001688:Biological Products / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D059451:Biosimilar Pharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017277:Drug Approval / Q000379:methods; D004345:Drug Industry / Q000379:methods* / Q000639:trends; D004358:Drug Therapy / Q000379:methods* / Q000639:trends; D005062:European Union; D006801:Humans; D013810:Therapeutic Equivalency
chemical_list: D001688:Biological Products; D059451:Biosimilar Pharmaceuticals
keywords: biosimilar; comparability; follow-on biologicals; regulatory expectations; safety