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Paediatric investigation plans

A paediatric investigation plan (PIP) is a development plan aimed at ensuring that the necessary data are obtained through studies in children, to support the authorisation of a medicine for children. All applications for marketing authorisation for new medicines have to include the results of studies as described in an agreed PIP, unless the medicine is exempt because of a deferral or waiver.

This requirement also applies when a marketing-authorisation holder (MAH) wants to add a new indication, pharmaceutical form or route of administration for a medicine that is already authorised and covered by intellectual property rights.

Guideline on the format and content of applications for agreement or modification of a paediatric investigation plan and requests for waivers or deferrals and concerning the operation of the compliance check and on criteria for assessing significant studies

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According to Article 16 of the Paediatric Regulation, applications should be submitted, unless duly justified, 'not later than upon completion of the human pharmaco-kinetic (PK) studies', as specified in Section 5.2.3 of Part 1 of Annex 1 of Directive 2001/83/EC. Recital 10 of the Regulation states that 'paediatric investigation plans should be submitted early during product development, in time for studies to be conducted in the paediatric population, where appropriate, before marketing authorisation applications are submitted. It is appropriate to set a deadline for the submission of a PIP in order to ensure early dialogue between the sponsor and the Paediatric Committee’.

The timing of submission should not be later than the end of healthy subject or patient PK, which can coincide with the initial tolerability studies, or the initiation of the adult phase-II studies (proof-of-concept studies); it cannot be after initiation of pivotal trials or confirmatory (phase-III) trials. Applicants are welcome to submit their PIP applications during or even before initial PK studies in adults. Submitting a PIP application for a new active substance during confirmatory or phase-III trials in adults, or after starting clinical trials in children, is likely to be considered unjustified.

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