title: Establishing medical plausibility in the context of orphan medicines designation in the European Union.
abstract: In the European Union, sponsors have the responsibility to demonstrate the "intention to diagnose, prevent or treat" a serious and rare condition before the Committee of Orphan Medicinal Products (COMP), for a medicinal product to meet the criteria for Orphan Designation. This requirement is commonly referred to as "medical plausibility" and the justification of this intention is assessed on the merits of each application by the COMP, which deliberates over the scientific evaluation of the evidence submitted. The scientific assessment of the applications for orphan designation by the Committee is based on the review of non-clinical (such as in vitro and in vivo) and/or clinical data submitted by the sponsor. Several challenges regarding the evidence provided emerge when the sponsor is applying for a designation at an early stage of development. Herein we discuss specific examples from the experience of the COMP, in order to elaborate on the type and level of evidence generally considered necessary for the purpose of justification of the intention to treat an orphan condition. Importantly, it is pointed out that bridging of data from other products, irrespectively of how comparable they may be, or from settings not directly associated with the condition as applied for designation, is by and large not a successful exercise and may only be exceptionally considered. It is further exemplified that, as reflected in the updated 'Guideline on the format and context of the applications for designation' and the guidance document 'Recommendation on elements required to support the medical plausibility and the assumption of significant benefit for an orphan designation' available on the EMA website, the sponsor should provide data with the specific product as applied for in specific models of the condition or in patients affected by the same condition subject of each application.
authors.affiliation: Orphan Medicines Office, European Medicines Agency, 7 Westferry Circus, Canary Wharf, E144HB, London, UK. Stylianos.Tsigkos@ema.europa.eu.
authors.forename: Stelios
authors.initials: S
authors.lastname: Tsigkos
authors.affiliation: Orphan Medicines Office, European Medicines Agency, 7 Westferry Circus, Canary Wharf, E144HB, London, UK. segundo.mariz@ema.europa.eu.
authors.forename: Segundo
authors.initials: S
authors.lastname: Mariz
authors.affiliation: Orphan Medicines Office, European Medicines Agency, 7 Westferry Circus, Canary Wharf, E144HB, London, UK. jordi.llinares@ema.europa.com.
authors.forename: Jordi
authors.initials: J
authors.lastname: Llinares
authors.affiliation: Orphan Medicines Office, European Medicines Agency, 7 Westferry Circus, Canary Wharf, E144HB, London, UK. laura.fregonese@ema.europa.eu.
authors.forename: Laura
authors.initials: L
authors.lastname: Fregonese
authors.affiliation: Orphan Medicines Office, European Medicines Agency, 7 Westferry Circus, Canary Wharf, E144HB, London, UK. stiina.aarum@ema.europa.eu.
authors.forename: Stiina
authors.initials: S
authors.lastname: Aarum
authors.forename: Frauke
authors.initials: F
authors.lastname: Naumann-Winter
authors.affiliation: Bundesinstitut für Arzneimittel und Medizinprodukte, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany. Frauke.Naumann-Winter@bfarm.de.
authors.forename: Naumann-Winter
authors.initials: NW
authors.lastname: Frauke
authors.affiliation: Läkemedelsverket, Dag Hammarskjölds vägen 42, 75103, Uppsala, Sweden. kerstin.westermark@mpa.se.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Westermark
authors.affiliation: Research Institute for Medicines (iMED.ULisboa), Faculty of Pharmacy, University of Lisbon, 1649-003, Lisboa, Portugal. bruno.sepodes@ema.europa.eu.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sepodes
mesh_terms: D017277:Drug Approval; D005062:European Union; D006801:Humans; D009965:Orphan Drug Production; D035583:Rare Diseases / Q000188:drug therapy*