21 Evaluation 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
22 Applications assessed by FWG Around 1000 PIPs validated PIP/waiver applications (March 2011)60%15/m
23 Critical 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
24 Regulatory references 2 (Draft) Guideline on pharmaceutical development of medicines for paediatric useCollaborative work between QWP, PDCO, and external experts.Public consultation aimed very soon.
27 WGroups Non-Clinical Opportunity StartClockStopClockReStartClockOpinionDAY 0 or 30DAY 60 or 90Opportunityto discuss need for juvenile animal studiesOpportunityto discuss need for juvenile animal studies
29 WGroups Methodology Opportunity Opportunity StartClockStopClockReStartClockOpinionDAY 0 or 30DAY 60 or 90Opportunityto discuss extrapolations statistics ?modellingOpportunityto discuss extrapolations statistics ?modelling
30 Reasonable 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
31 Prevalence Diagnosis Project Resources Protocol Methodological constraints in small populationsOverall populationPrevalenceAffected populationDiagnosisSick population(patients)ProjectAvailable Population(volunteers)ResourcesParticipatingPopulation(Cases)Protocol“Classical Power”CT
33 Definition 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
39 6% 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%
40 PDCO Achievements Plan Implementation of proceduresPIP Evaluation and OutcomesSurvey of the NeedsPriority list & FP7EnpremaChallenges
41 REPORT 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
42 Results (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.
43 Results (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)
44 Results (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.
45 PDCO Achievements Plan Implementation of proceduresPIP Evaluation and OutcomesSurvey of the NeedsPriority list & FP7EnpremaChallenges
57 Scientific Advice (paediatric only) SA +PAPaed%20072817.520083207.220093887.7201040085757
58 PDCO 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
59 Take home messageGood research in children is a need & time is needed to develop good research