title: Interchangeability of Biosimilars: A European Perspective.
abstract: Many of the best-selling 'blockbuster' biological medicinal products are, or will soon be, facing competition from similar biological medicinal products (biosimilars) in the EU. Biosimilarity is based on the comparability concept, which has been used successfully for several decades to ensure close similarity of a biological product before and after a manufacturing change. Over the last 10 years, experience with biosimilars has shown that even complex biotechnology-derived proteins can be copied successfully. Most best-selling biologicals are used for chronic treatment. This has triggered intensive discussion on the interchangeability of a biosimilar with its reference product, with the main concern being immunogenicity. We explore the theoretical basis of the presumed risks of switching between a biosimilar and its reference product and the available data on switches. Our conclusion is that a switch between comparable versions of the same active substance approved in accordance with EU legislation is not expected to trigger or enhance immunogenicity. On the basis of current knowledge, it is unlikely and very difficult to substantiate that two products, comparable on a population level, would have different safety or efficacy in individual patients upon a switch. Our conclusion is that biosimilars licensed in the EU are interchangeable.
authors.affiliation: Finnish Medicines Agency, FIMEA, Mannerheimintie 103b, P.O. Box 55, 00034, Helsinki, Finland. pekka.kurki@fimea.fi.
authors.forename: Pekka
authors.initials: P
authors.lastname: Kurki
authors.affiliation: Medicines Evaluation Board, P.O. Box 8275, 3503 RG, Utrecht, The Netherlands.
authors.forename: Leon
authors.initials: L
authors.lastname: van Aerts
authors.affiliation: Paul-Ehrlich-Institut (PEI), Paul-Ehrlich-Straße 51-59, 63225, Langen, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Wolff-Holz
authors.affiliation: Foundation Pharmacy for Hospitals in Haarlem, Boerhaavelaan 24, 2035 RC, Haarlem, The Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: Giezen
authors.affiliation: Norwegian Medicines Agency, Sven Oftedalsvei 6, 0950, Oslo, Norway.
authors.forename: Venke
authors.initials: V
authors.lastname: Skibeli
authors.affiliation: Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.
authors.forename: Martina
authors.identifier: http://orcid.org/0000-0002-7767-4113
authors.initials: M
authors.lastname: Weise
mesh_terms: D000068879:Adalimumab / Q000009:adverse effects / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects* / Q000493:pharmacokinetics; D004345:Drug Industry / Q000379:methods; D000068817:Epoetin Alfa / Q000009:adverse effects; D000068800:Etanercept / Q000009:adverse effects / Q000627:therapeutic use; D005062:European Union; D000069585:Filgrastim / Q000009:adverse effects; D019382:Human Growth Hormone / Q000009:adverse effects; D006801:Humans; D007107:Immune System / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D059451:Biosimilar Pharmaceuticals; C000591237:CT-P13; D019382:Human Growth Hormone; D000068817:Epoetin Alfa; D000068879:Adalimumab; D000068800:Etanercept; D000069585:Filgrastim