title: Classification of Recombinant Biologics in the EU: Divergence Between National Pharmacovigilance Centers.
abstract: OBJECTIVE
  Biological medicinal products (biologics) are subject to specific pharmacovigilance requirements to ensure that biologics are identifiable by brand name and batch number in adverse drug reaction (ADR) reports. Since Member States collect ADR data at the national level before the data is aggregated at the European Union (EU) level, it is important that an unambiguous understanding of which medicinal products belong to the biological product category exists. This study aimed to identify the level of consistency between Member States regarding the classification of biologics by national authorities responsible for ADR reporting.
  
  
  METHODS
  A sample list of recombinant biologics from the European Medicines Agency database of European Public Assessment Reports was created to analyze five Member States (Belgium, the Netherlands, Spain, Sweden, and the UK) according to which products were classified as biologics by each Member State. We calculated the Fleiss kappa value to analyze interrater reliability.
  
  
  RESULTS
  A considerable divergence was identified regarding the classification of the 146 recombinant biologics from the sample list: one Member State classified 100 % of the recombinant biologics from the sample list as biologics, whereas the classification rates in the remaining four Member States ranged between 70 and 88 % for products available on the national market. The interrater reliability for 87 products available on the market in all five Member States was considered poor.
  
  
  CONCLUSIONS
  Discrepancies exist between Member States in the classification of biologics; less divergence exists for common well-known biologics. These findings highlight the need to think about the best approaches to translate EU legislation into national practices. Additionally, we recommend a publicly available and frequently updated list of centrally authorized biologics.
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands. k.klein@escher-project.org.|TI Pharma Escher, Galileiweg 8, 2333BD, Leiden, The Netherlands. k.klein@escher-project.org.|Exon Consultancy, Amsterdam, The Netherlands. k.klein@escher-project.org.
authors.forename: Kevin
authors.initials: K
authors.lastname: Klein
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands. M.L.deBruin@uu.nl.
authors.forename: Marie L
authors.initials: ML
authors.lastname: De Bruin
authors.affiliation: TI Pharma Escher, Galileiweg 8, 2333BD, Leiden, The Netherlands.
authors.forename: Andre W
authors.initials: AW
authors.lastname: Broekmans
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.|TI Pharma Escher, Galileiweg 8, 2333BD, Leiden, The Netherlands.|Exon Consultancy, Amsterdam, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Stolk
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000592:standards; D001688:Biological Products / Q000145:classification* / Q000592:standards; D016208:Databases, Factual / Q000145:classification / Q000592:standards; D005062:European Union; D006801:Humans; D007880:Legislation, Drug / Q000592:standards; D060735:Pharmacovigilance; D011994:Recombinant Proteins / Q000145:classification / Q000592:standards
chemical_list: D001688:Biological Products; D011994:Recombinant Proteins