title: Oral medicines for children in the European paediatric investigation plans.
abstract: BACKGROUND
  Pharmaceutical industry is no longer allowed to develop new medicines for use in adults only, as the 2007 Paediatric Regulation requires children to be considered also. The plans for such paediatric development called Paediatric Investigation Plans (PIPs) are subject to agreement by the European Medicines Agency (EMA) and its Paediatric Committee (PDCO). The aim of this study was to evaluate the key characteristics of oral paediatric medicines in the PIPs and the changes implemented as a result of the EMA/PDCO review.
  
  
  METHODS
  All PIPs agreed by 31 December 2011 were identified through a proprietary EMA-database. PIPs were included if they contained an agreed proposal to develop an oral medicine for children 0 to 11 years. Information on the therapeutic area (EMA classification system); target age range (as defined by industry) and pharmaceutical characteristics (active substance, dosage form(s) as listed in the PIP, strength of each dosage form, excipients in each strength of each dosage form) was extracted from the EMA website or the EMA/PDCO assessment reports.
  
  
  RESULTS
  A hundred and fifty PIPs were included corresponding to 16 therapeutic areas and 220 oral dosage forms in 431 strengths/compositions. Eighty-two PIPs (37%) included tablets, 44 (20%) liquids and 35 (16%) dosage forms with a specific composition/strength that were stored as a solid but swallowed as a liquid e.g. dispersible tablets. The EMA/PDCO review resulted in an increase of 13 (207 to 220) oral paediatric dosage forms and 44 (387 to 431) dosage forms with a specific composition/strength. For many PIPs, the target age range was widened and the excipient composition and usability aspects modified.
  
  
  CONCLUSIONS
  The EMA/PDCO review realized an increase in the number of requirements for the development of oral dosage forms and a larger increase in the number of dosage forms with a specific composition/strength, both targeting younger children. Changes to their pharmaceutical design were less profound.
authors.affiliation: Medicines Evaluation Board in the Netherlands (MEB), Department of Chemical Pharmaceutical Assessment, Utrecht, the Netherlands; Utrecht University, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences (UIPS), Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht, the Netherlands.
authors.forename: Diana A
authors.initials: DA
authors.lastname: van Riet-Nales
authors.affiliation: Utrecht University, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences (UIPS), Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht, the Netherlands.
authors.forename: Erwin G A W
authors.initials: EG
authors.lastname: Römkens
authors.affiliation: European Medicines Agency, Human Medicines Special Areas, London, United Kingdom.
authors.forename: Agnes
authors.initials: A
authors.lastname: Saint-Raymond
authors.affiliation: European Medicines Agency, Quality of Medicines, London, United Kingdom.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kozarewicz
authors.affiliation: Medicines Evaluation Board in the Netherlands (MEB), Department of Chemical Pharmaceutical Assessment, Utrecht, the Netherlands; Utrecht University, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences (UIPS), Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht, the Netherlands.
authors.forename: Alfred F A M
authors.initials: AF
authors.lastname: Schobben
authors.affiliation: Utrecht University, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences (UIPS), Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht, the Netherlands; University Medical Centre Utrecht, Department of Clinical Pharmacy, Utrecht, the Netherlands.
authors.forename: Toine C G
authors.initials: TC
authors.lastname: Egberts
authors.affiliation: University Medical Centre Utrecht, Department of Clinical Pharmacy, Utrecht, the Netherlands.
authors.forename: Carin M A
authors.initials: CM
authors.lastname: Rademaker
mesh_terms: D000284:Administration, Oral; D026683:Advisory Committees; D002648:Child; D002675:Child, Preschool; D062313:Databases, Pharmaceutical; D004304:Dosage Forms; D004345:Drug Industry; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D055553:Prescription Drugs / Q000008:administration & dosage*
chemical_list: D004304:Dosage Forms; D055553:Prescription Drugs