title: Causes of drug shortages in the legal pharmaceutical framework.
abstract: BACKGROUND
  Different causes of drug shortages can be linked to the pharmaceutical legal framework, such as: parallel trade, quality requirements, economic decisions to suspend or cease production, etc. However until now no in-depth study of the different regulations affecting drug shortages is available. The aim of this paper is to provide an analysis of relevant legal and regulatory measures in the European pharmaceutical framework which influence drug shortages.
  
  
  METHODS
  Different European and national legislations governing human medicinal products were analyzed (e.g. Directive 2001/83/EC and Directive 2011/62/EU), supplemented with literature studies.
  
  
  RESULTS
  For patented drugs, external price referencing may encompass the largest impact on drug shortages. For generic medicines, internal or external reference pricing, tendering as well as price capping may affect drug shortages. Manufacturing/quality requirements also contribute to drug shortages, since non-compliance leads to recalls. The influence of parallel trade on drug shortages is still rather disputable.
  
  
  CONCLUSIONS
  Price and quality regulations are both important causes of drug shortages or drug unavailability. It can be concluded that there is room for improvement in the pharmaceutical legal framework within the lines drawn by the EU to mitigate drug shortages.
authors.affiliation: KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Herestraat 49, PO Box 521, 3000 Leuven, Belgium. Electronic address: elfi.deweerdt@pharm.kuleuven.be.
authors.forename: Elfi
authors.initials: E
authors.lastname: De Weerdt
authors.affiliation: KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Herestraat 49, PO Box 521, 3000 Leuven, Belgium. Electronic address: steven.simoens@pharm.kuleuven.be.
authors.forename: Steven
authors.initials: S
authors.lastname: Simoens
authors.affiliation: KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Herestraat 49, PO Box 420, 3000 Leuven, Belgium. Electronic address: luc.hombroeckx@pharm.kuleuven.be.
authors.forename: Luc
authors.initials: L
authors.lastname: Hombroeckx
authors.affiliation: KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Herestraat 49, PO Box 521, 3000 Leuven, Belgium. Electronic address: minne.casteels@kuleuven.be.
authors.forename: Minne
authors.initials: M
authors.lastname: Casteels
authors.affiliation: KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Herestraat 49, PO Box 521, 3000 Leuven, Belgium. Electronic address: Isabelle.huys@pharm.kuleuven.be.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Huys
mesh_terms: D003365:Costs and Cost Analysis / Q000191:economics / Q000331:legislation & jurisprudence; D004345:Drug Industry / Q000191:economics / Q000331:legislation & jurisprudence*; D016568:Drugs, Generic / Q000191:economics; D005062:European Union; D006297:Health Services Accessibility / Q000191:economics / Q000331:legislation & jurisprudence*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000191:economics; D012051:Reimbursement Mechanisms / Q000331:legislation & jurisprudence; D006113:United Kingdom; D014481:United States
chemical_list: D016568:Drugs, Generic; D004364:Pharmaceutical Preparations
keywords: Drug shortages; Legal framework; Market authorization; Parallel trade; Pricing; Quality requirements; Quota