PDCO EMA Update AMK 13-06-2017

1 PDCO / EMA updateChallenges and opportunities in paediatric developmentAnn Marie Kaukonen, Researcher, Pharmaceutical AssessorPDCO member, PDCO FWG memberJoint NORDICPedMed / PIF Nordic Conference on Pediatric Medicines 13th June, Helsinki, Finland L kealan turvallisuus- ja kehitt miskeskus The views expressed in this presentation are the personal views of the presenter and may not be understood or quoted as being made on behalf of or reflecting the position of the Finnish Medicines Agency, the European Medicines Agency or any of its committees or working Paed Conference - AMK2 DisclaimerL kealan turvallisuus- ja kehitt miskeskusStructure Background - paediatric Regulation and PIPs Dialogue with PDCO/EMA Global interaction EMA / FDA Enpr-EMA2017-06-13 Nordic Paed Conference - AMK3L kealan turvallisuus- ja kehitt miskeskus2017-06-13 Nordic Paed Conference - AMK4 Background Regulation (EC) No 1901/2006 2007: entry into force 2017: EC to present report to EP (Article 50 (3)) EMA report on the objectives of the regulation:1.

2 More medicines for children2. More information for prescribers & patients3. Ethical high-quality researchL kealan turvallisuus- ja kehitt miskeskus2017-06-13 Nordic Paed Conference - AMK5A system of obligations and rewards New medicines (and new indications, new routes of administration, new pharmaceutical forms) must have an agreed paediatric Investigation Plan (PIP) or a waiver at time of marketing authorisation application Submission of draft PIP or waiver no later than completion of adult PK studies (generally understood as end of phase 1) Agreement of PIP with the paediatric Committee (PDCO) Reward is 6-month extension of Supplementary Protection Certificate (EU medicine patent extension, but not available to all medicines)

3 Voluntary process for off-patent medicinesL kealan turvallisuus- ja kehitt miskeskusPaediatric Committee (PDCO)2017-06-13 Nordic Paed Conference - AMK6+ alternatesL kealan turvallisuus- ja kehitt miskeskus2017-06-13 Nordic Paed Conference - AMK7 paediatric Investigation PlanBinding contract to perform agreed studies paediatric formulation(s) (appropriate for age and condition) Pre-clinical studies (pot. juvenile; toxicology, disease models; excipients) Clinical studies (efficacy, safety, PK/PD, acceptability of formulations) Timelines (and interdependency) for each componentFormulationToxicology,PK, PD, carcino, genotoxjuvenile animalsSafety -Proof ofconceptDose-Finding -PKEfficacySafety issuesL kealan turvallisuus- ja kehitt miskeskusWherewearetoday 10 years from first PDCO meeting in July 2017 966 agreed PIPs by May of 20172017-06-13 Nordic Paed Conference - AMK8L kealan turvallisuus- ja kehitt miskeskusModifications of agreed PIPs2017-06-13 Nordic Paed Conference - AMK9 Numbers increasing, now appr.

4 200 procedures per year Timelines, trial design (sample size, endpoints, dosing), formulationsL kealan turvallisuus- ja kehitt miskeskus2017-06-13 Nordic Paed Conference - AMK10 Based on deferral reportsOnly applies to already authorised products (not before MA)Recruitment difficulties ( )Problems with PIP progressIrmgard Eichler: Enpr-EMA webinar Dec 201610-year Report to EC on the paediatric kealan turvallisuus- ja kehitt miskeskusPIP life-cyclePlanning paediatric development and the PIP paediatric needs / previous PIPs Scientific guidelines and workshops Enpr-EMA, paediatric networks, patient organisations, YPAGs, Expert groups2017-06-13 Nordic Paed Conference - AMK11 PIP agreed with PDCO / EMA EMA Early interaction meetings (pilot) Pre-submission / Clarification TC Oral explanations at PDCOPIP ProgressModifications of agreed PIPL kealan turvallisuus- ja kehitt miskeskusEarly paediatric interaction meetings (EPIM)

5 Request from industry for early dialogue with the PDCO Pilot initiated in June 2015 to explore concept Takes place at an early stage of development EMA Paediatrics and PDCO representative(s) involved Possibility to discuss overall development strategy paediatric needs and scope of development in children Integration to adult development Avoiding unnecessary studies in children Possible extrapolation Appropriateness of waiver Not intended to evaluate data to support PIP application2017-06-13 Nordic Paed Conference - AMK12L kealan turvallisuus- ja kehitt miskeskusAnalysis after 22 months experience2017-06-13 Nordic Paed Conference - AMK13 Gunter Egger: Early dialogue on paed development plans, April 25.

6 2017 Industry stakeholder platform on research and development supportL kealan turvallisuus- ja kehitt miskeskusPre-submission meeting When PIP is nearly ready for submission Purpose to ensure smooth validation Not a pre-assessment of the scientific documentation Offered as teleconference to all applicants Request at least two months prior to planned PIP submission At least paediatric co-ordinator and rapporteur present2017-06-13 Nordic Paed Conference - AMK14 Clarification teleconference Clarify the PDCO position and Request for Modifications to facilitate the preparation of answers At least paediatric co-ordinator and rapporteur present Not a pre-assessment of the scientific documentationL kealan turvallisuus- ja kehitt miskeskusOral explanations in front of PDCO Invitation by the Committee to discuss issues in relation to their application Applicants may request a meeting with the Committee Opportunity for both to present their position Particularly to explain a negative PDCO position Major discrepancies exist, which cannot be resolved within the remaining timeframe External experts may be invited (by PDCO and/or applicant) Last resort due to time restrictions at the meetings2017-06-13 Nordic Paed Conference - AMK15L kealan turvallisuus- ja kehitt miskeskusGlobal collaboration paediatric Cluster EMA/FDA, extended to PMDA (Jp), TGA (AUS)

7 , also Health Canada Started in 2012, monthly teleconferences Both specific products and general issues Information exchange, understanding of (different) scientific views, harmonisation where possible Joint Working Groups, Workshops and Expert Meetings for extended discussions Gaucher disease collaborative approach from the EMA and FDA June 12-13, 2017 EMA/FDA/Health Canada joint workshop addressing unmet needs of children with pulmonary arterial hypertension Revision of ICH E112017-06-13 Nordic Paed Conference - AMK16L kealan turvallisuus- ja kehitt miskeskusEnpr-EMAE uropean Network of paediatric Research at the European Medicines Agency2017-06-13 Nordic Paed Conference - AMK17 Enpr-EMA- umbrella network of existing European networks provides access to networks/sites with expertise in performing clinical trials in the paediatric population enables collaboration / learning of individual networks from each other Different role from the clinical trial networks.

8 Which actually conduct and perform the clinical trials Member networks perform research with children (newborns to adolescents), in multiple therapeutic areas, and ranging from pharmacokinetics to pharmacovigilance L kealan turvallisuus- ja kehitt miskeskusEnpr-EMA2017-06-13 Nordic Paed Conference - AMK18 Platform for close interactions of all stakeholders necessary to facilitate the conduct of (large) studies in children To link together existing networks EU and extra-EU To share best practices To offersingle point of contact for (European) networks To define strategies for resolving major challenges Enpr-EMA does NOT fund / conduct clinical trials act as a CRO and manage studiesL kealan turvallisuus- ja kehitt miskeskus2017-06-13 Nordic Paed Conference - AMK19 What Enpr-EMA can offer to industry Expert advice Treatment options (standard of care)

9 paediatric needs Feasibility of paediatric clinical trials Pool of patients for inclusion - Speeding up recruitment Neutral platform for multi-stakeholder meetings with investigators, networks, patient/parents, regulators Access to academic partners through collaboration with EMA s SME officeL kealan turvallisuus- ja kehitt miskeskusMember networks and Enpr-EMA activities At the end of 2016, Enpr-EMA has 39 networks registered in the Enpr-EMA database (fully searchable) Annual workshops at the EMA Working groups Dialogue and interaction with Ethics Committees Sharing good practices within Enpr-EMA and with industry Neonatology Young Persons Advisory Groups (YPAGs) Educational Training of Research Staff involved in paediatric CTs Clinical trial designs for paediatric antibiotic trials Regular meetings with the paediatric Committee - initiated in 20162017-06-13 Nordic Paed Conference - AMK20L kealan turvallisuus- ja kehitt miskeskus2017-06-13 Nordic Paed Conference - AMK21 Fully searchable Enpr-EMA database L kealan turvallisuus- ja kehitt miskeskusWhere to find Enpr-EMA on EMA homepage2017-06-13 Nordic Paed Conference - AMK22L kealan turvallisuus- ja kehitt miskeskusThank you for you attention!

10 Please feel free to ask questions now or laterEmail: at Paed Conference - AMK23