title: Reflections on Decisions Made on the Well-Established Use of Medicinal Products by EU Regulators and the ECJ.
abstract: In the European Union (EU), a medicinal product needs a marketing authorization (MA) to be placed on the market. The EU's medicinal products' legislative framework allows for a reduced application for medicines outside their data exclusivity. One such type of application is the well-established use (WEU) medicinal product application (i.e. bibliographic applications). Recently, these MA applications have been subject to arbitration procedures at the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) because of disagreements between member states during the authorisation process. This paper reflects on these cases and highlights their potential impact on future WEU applications.
  
  
  
  Decisions adopted by the European Commission on WEU applications between 2009 and 2012 were identified from the EU Community Register on medicinal products for human use. Subsequently, decisions were reviewed to understand the potential serious risk to public health (PSRPH) that EU regulators raised during MA application procedures.
  
  
  
  Four decisions were adopted by the EU commission between 2009 and 2012. Three followed disagreements between member states on PSRPH grounds. One decision was the outcome of a centralised marketing authorisation application. Six key messages were identified from the four cases reviewed and presented.
  
  
  
  A guideline on WEU to implement the technical specifications to fulfil Annex I of Directive 2001/83/EC for MA applications is not available. Thus, reflections on recent decisions on WEU applications provide scientific direction to the industry as well as the medicinal product regulators on the documentation required to successfully file and obtain a WEU MA.
authors: Medicines Authority, 203 Level 3, Rue D'Argens, Gzira, GZR 1368, Malta; School of Pharmacy, University of Tor Vergata, Rome, Italy.
authors: John Joseph
authors: JJ
authors: Borg
authors: BASG/AGES Medizinmarktaufsicht, Traisengasse 5, A-1200 Vienna, Austria.
authors: Andrea
authors: A
authors: Laslop
authors: Italian Mediciens Agency, AIFA, Via del Tritone, 181, 00186 Rome, Italy.
authors: Luca
authors: L
authors: Pani
authors: State Medicines Control Agency, Savanoriu, pr 220, LT-50148 Kaunas, Lithuania; Institute of Physiology and Pharmacology, Nephrology Clinic, Lithuanian Health Science University, A. Mickevičiaus g. 9, Kaunas LT-44307, Kaunas, Lithuania.
authors: Romaldas
authors: R
authors: Maciulaitis
authors: Department of Physiology and Pharmacology, University of Rome "Sapienza", Rome, Italy.
authors: Daniela
authors: D
authors: Melchiorri
keywords: Abridged applications; Generics; Medicinal products; Regulatory affairs; Well-established use