21Evaluation procedure of PIPs PDCO FWG Formulation Group – monthly meetingPDCO members (Chair: Dr Siri Wang) + external experts (hospital, academia).Discussion on formulation aspects and reporting to the PDCO.PDCO Paediatric Committee - monthly meeting
22Applications assessed by FWG Around 1000 PIPs validated PIP/waiver applications (March 2011)60%15/m
23Critical Points for Paediatric Formulations Route of administrationAppropriate dosage formsExcipients - 50% of the PIPs- choice excipient, safety, level, side effects……Taste and palatabilityDelivery devicesRate of infusionVolume to be administeredWastage23
24Regulatory references 2 (Draft) Guideline on pharmaceutical development of medicines for paediatric useCollaborative work between QWP, PDCO, and external experts.Public consultation aimed very soon.
27WGroups Non-Clinical Opportunity StartClockStopClockReStartClockOpinionDAY 0 or 30DAY 60 or 90Opportunityto discuss need for juvenile animal studiesOpportunityto discuss need for juvenile animal studies
29WGroups Methodology Opportunity Opportunity StartClockStopClockReStartClockOpinionDAY 0 or 30DAY 60 or 90Opportunityto discuss extrapolations statistics ?modellingOpportunityto discuss extrapolations statistics ?modelling
30Reasonable to assume equivalence of disease Children = Adults - similar progression?- similar response to intervention?NoYesYesConduct PK studiesConduct S & E trialsReasonable to assume similar concentration response (C-R) in Children = Adults?NoYesIs there a PD measurement that can be used to predict E?Conduct PK studies to achieve levels similar to AdultsConduct S trialsNoYesConduct PK/PD studies to get CR for PD measurementConduct PK to achieve target concentration based on CRConduct S & E trials
31Prevalence Diagnosis Project Resources Protocol Methodological constraints in small populationsOverall populationPrevalenceAffected populationDiagnosisSick population(patients)ProjectAvailable Population(volunteers)ResourcesParticipatingPopulation(Cases)Protocol“Classical Power”CT
33Definition of Models Published Paradigm PBPK (Physiologically Based PK)PBPK-PDPOP PK (Population Based PK)POP PK/PDDisease progression models and response modelsKinetic (K)–PD modelsToxicity/AE models
396% How many trials have effectively started? How many children to be included?How many indications to be developed?What is the expected product attrition rate?What are finalisation delays overall?6%
40PDCO Achievements Plan Implementation of proceduresPIP Evaluation and OutcomesSurvey of the NeedsPriority list & FP7EnpremaChallenges
41REPORT ON THE SURVEY OF ALL PAEDIATRIC USES OF MEDICINAL PRODUCTS IN EUROPE established according to article 42of Regulation (EC) No 1901/2006of the European Parliament and of the Councilon medicinal products for paediatric usePresented by: Dr. Radu BotgrosScientific Administrator, Safety and Efficacy of Medicines
42Results (I) mainly in Scandinavia. Most frequent medicines used off-label/ unauthorised:antiarrhythmics,antihypertensives (rennin-angiotensin inhibitors and beta- blockers),proton pump inhibitors and H2-receptor antagonists,antiasthmatics, andantidepressants (mainly selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and tricyclic antidepressants).High rate of off-label use of oral contraceptives in adosmainly in Scandinavia.
43Results (II) Extensive off-label use of ABs in very young children. macrolidesbetalactamines plus betalactamase inhibitorscarbapenemsCorticosteroids used off-label in the systemic treatment of very young children.Some for systemic use (e.g. dexamethasone) are not even authorised in some countries (Norway)
44Results (III) Analysis of the pharmaceutical forms off-label use of both oral and parenteral formulations are being used unauthorised or off-label,common reason: lack of appropriate dosages and strengths for the treated age groups.off-label use ofmultivitaminsmany antiasthmatics.
45PDCO Achievements Plan Implementation of proceduresPIP Evaluation and OutcomesSurvey of the NeedsPriority list & FP7EnpremaChallenges
57Scientific Advice (paediatric only) SA +PAPaed%20072817.520083207.220093887.7201040085757
58PDCO Achievements Conclusion Change of mindset with Industry475 PIPs agreedStart of Network of NetworksLimited view of immediate impact…Better overview of Paediatric needsTrials of off-label drugs (FP7)Reflection ongoing to improve/ facilitate work
59Take home messageGood research in children is a need & time is needed to develop good research