EU Paediatric Regulation EU Paediatric Regulation How to prepare PIP/waiwer How to prepare PIP/waiwer dossier? dossier? EMEA SME workshop EMEA SME workshop October 23, EMEA, London October 23, EMEA, London Anu Tummavuori Associate Director European Regulatory Liaison Celgene, Switzerland Anu Tummavuori 1
Overview Overview • EU Paediatric Regulation – what does it mean in practise? • Where to start for PIP/waiver – what needs to be considered? • How to get it to EMEA and pass validation? Anu Tummavuori 2
3 EU Paediatric Regulation EU Paediatric Regulation Anu Tummavuori
Objectives of the Paediatric Regulation Objectives of the Paediatric Regulation � Improve the health of children • Increase high quality, ethical research into medicines for children • Increase availability of authorised medicines for children • Increase information on use of medicines in children � Achieve the above • Without unnecessary studies in children • Without delaying authorisation for adults � Development of medicines for children should be an integral part of the development of medicinal product � Integrated into the development program for adults Anu Tummavuori 4
What is a PIP? What is a PIP? • Roadmap to obtain paediatric indication (and formulation) • Same criteria as for MAA (Q, S & E) • Basis for the reward • No “PIP light” Anu Tummavuori 5
Need a PIP because of Need a PIP because of Paediatric Regulation states that there is an obligation to submit results of paediatric studies compliant with PIP, or a waiver or deferral, in Module 1 of Approved product (Art 8) when new New Products (Art 7): indication, route of administration, - MAA application formulation: - Need to cover MAA - Variation/line-extension application* indication(s) - Need to cover all existing and - All new products new indications irrespective of - Only products with SPC (or patent patent status qualifying for SPC) *new/change to indication, new formulation, new route of administration Anu Tummavuori 6
What does PIP & Waiver need to cover? What does PIP & Waiver need to cover? - Example for overview for a product - Example for overview for a product Pre-term Term Infants & Children Adolescents newborn newborn toddlers (2-11 years) infants infants (28 d - 23 m) (12-17 y) (0-27 days) Class waiver Class waiver Class waiver Class waiver Class waiver Adult indication A Waiver Waiver PIP including PIP including PIP including Adult deferrals & deferrals & deferrals & indication B formulation formulation formulation development development development PIP including PIP including PIP including Waiver Waiver Paediatric deferrals & deferrals & deferrals & indication formulation formulation formulation development development development Anu Tummavuori 7
When to submit PIP? When to submit PIP? Products in development: - Regulation: end of Phase 1 - Well in time for having PIP approved, and compliance check done before MAA filing Products already approved: -Well in time for having PIP approved, and compliance check done before variation/line-extension filing Worthwhile to consider: - reward opportunities (timing for having Pae studies in MA) - withdrawal/re-submission of PIP - impact on due diligence Anu Tummavuori 8
PIP compliance PIP compliance • Compliance = verification that the measures agreed in PIP & Decision have been conducted in accordance with the decision including the timelines • Is needed for 2 instances 1) filing of MAA/extension/indication submission (unless relevant conditions waived or deferred) 2) pre-requisite for obtaining the reward Anu Tummavuori 9
MAA/variaon/extension validation MAA/variaon/extension validation • Validation = verification that the applicant meets the administrative and legal dossier requirements, now including Paeditric Regulation • Is performed before assessment if no positive validation, the assessment will not start Anu Tummavuori 10
Validation and compliance Validation and compliance - Example for a product - Example for a product Pre-term Term Infants & Children Adolescents newborn newborn toddlers (2-11 years) (12-17 y) infants infants (28 d - 23 m) (0-27 days) Adult Waiver Waiver Waiver PIP* PIP Subject to compliance indication A: for MAA validation Subject to MAA Subject to compliance Adult Waiver Waiver PIP* PIP* PIP* indication for indication filing B: Subject to validation filing later Paediatric PIP* PIP* PIP* Waiver Waiver Subject to compliance indication for completed PIP validation for reward * Must include formulation development (if applicable) Anu Tummavuori 11
Validation Decision Tree Validation Decision Tree - PIP with (partial) deferral - PIP with (partial) deferral Is it relevant to indication applied for? Yes Have the results that are needed been submitted ? No Yes Not Is there EMEA cover letter valid & PDCO report for these? No Yes Is it Validation compliant? Suspended & Referred to No Yes PDCO for Compliance for Not these needed VALID valid measures Anu Tummavuori 12
Preparing for PIP – what Preparing for PIP – what needs to be considered? needs to be considered? Anu Tummavuori 13
Question to ask about product? Question to ask about product? • Is this a new or already approved product? • Does the product have a SPC (patent)? • Does the product have an Orphan Designation? • Has/Is the product been/being registered in the US? Is there a WR? • Are the indications/conditions applicable for paediatric population? • Can the product be developed in other paediatric indications/conditions? Anu Tummavuori 14
EU and US: what needs to be done? EU and US: what needs to be done? Chemical NME Biotech Orphan Other EU Regulation Mandatory Mandatory Mandatory Voluntary PIP for MAA and for MAA and for MAA and + PUMA possible indications/ indications/ indications/ for product out of line extensions line extensions line extensions patent All adult indications All adult indications All adult indications + pae possible + pae possible + pae possible Reward possible Reward possible Reward possible Reward possible Mandatory to Mandatory to Does not apply PREA Not applicable include assessment, include assessment, to generics, US waiver or deferral in waiver or deferral in OTC NDAs/sNDAs NDAs/sNDAs No reward No reward Voluntary; Written Voluntary ; WR Not applicable BPCA Request (WR) linked to active US linked to active moiety, not NDA moiety, not NDA Reward possible Reward possible Anu Tummavuori 15
P(a)ediatric Plan + Waivers EU and US P(a)ediatric Plan + Waivers EU and US - Possible breakdown for “novel oncology biotech product” - Possible breakdown for “novel oncology biotech product” Pre-term ~0-1 month ~1– 24 months ~2-12 years ~12-(16) 17 newborns years Adult Waiver Waiver Waiver Waiver Waiver indication A: Waiver Waiver Waiver Waiver Breast Cancer Adult Waiver Waiver PIP including PIP including PIP including indication B: deferrals & deferrals & deferrals formulation formulation Leukemia development development Waiver PREA plan PREA plan with PREA plan with with deferrals deferrals, deferrals, formulation formulation development development Paediatric PIP incl PIP including PIP including Waiver Waiver indication: (not deferrals & deferrals & deferrals & planned) formulation formulation formulation Medullo- development development development WR not WR not blastoma WR not WR not possible possible possible possible Anu Tummavuori 16
Timing of pae submissions and Timing of pae submissions and discussions with FDA and EU regulators discussions with FDA and EU regulators EU meetings Scientific PIP/waiver EMEA + Advive End of Ph I Further included in MAA rapporteur/co- EMEA – PIP/waiver/ Scientific rappoteur pre- deferral Advice on SAWP submission + (CHMP) EMEA – PDCO development meetings PDCO compliance check and data included in MAA Development Phase I-III Pre-Submission Submission Must address PREA End of Ph I End of Ph II Pre-NDA meeting Pre-IND requirement in NDA meeting meeting meeting PREA plans (with assessment, Pediatric plan confirmed waiver, or deferral) (PREA +/- BPCA) should be discussed BPCA plans confirmed & WR issued pre- or post-approval FDA meetings: overall timing is product-specific, but PREA must be addressed in NDA Anu Tummavuori 17
The Rewards in the EU The Rewards in the EU Regulation has possibility for different rewards: 1. Patented products (products under patent which qualifies for SPC): + 6 months SPC extension or + 1 year on MP for innovative new pae indication 2. Orphan Medicinal Products: + 2 years extension to ME 3. Off-patent medicinal products: New type of MA: Paediatric Use Marketing Authorisation (PUMA) Anu Tummavuori 18
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