EMA Guidance: Procedural Advice on Paediatric Applications

The European Medicines Agency (EMA) has issued updated guidance "Procedural advice on Paediatric Applications" to support stakeholders in submitting paediatric applications in line with Regulation (EC) No 1901/2006 (Paediatric Regulation). This essential guide, revised as of 15 April 2025, outlines how to submit, modify, and manage Paediatric Investigation Plans (PIPs), request waivers, and complete compliance checks via the EMA’s IRIS portal. It is targeted at applicants developing medicinal products for children and aims to ensure ethical, scientifically robust research and better access to safe and effective paediatric medicines.

The Paediatric Regulation (EC) No 1901/2006 came into force with the primary objective of improving the health of children in Europe. It strives to achieve this by:

• Ensuring medicines for children are high quality, ethically researched, and appropriately authorized.

• Improving the availability of information about medicine use in children.

• Avoiding unnecessary trials in children and preventing delays in authorizing medicines for adults.

This regulation fundamentally reshaped the landscape for paediatric medicines in Europe, establishing the Paediatric Committee (PDCO) to coordinate the EMA's efforts in this area.

For medicinal products not authorized in the EU as of July 26, 2008, the following must be included for the application to be considered valid:

• Results of all studies and details of all information collected, conducted in compliance with an agreed paediatric investigation plan (PIP). The application must include the PIP decision and the results.

• An EMA decision on a PIP, including the granting of a deferral. If applicable, any completed studies must also be submitted.

• An EMA decision granting a product-specific waiver.

• An EMA decision granting a class waiver, along with the EMA confirmation letter of applicability (if requested).

Where results of paediatric studies are submitted, applicants must include a rationale in the clinical overview, supporting proposed changes to the Product Information.

The following types of Applications are exempt from Paediatric Requirements:

• Generic medicinal products

• Hybrid medicinal products

• Similar biological medicinal products

• Medicinal products containing active substance(s) of well-established medicinal use

While most paediatric procedure fees are waived, an administrative charge may apply in cases of:

• Application withdrawal post-submission.

• Negative validation outcomes.

Micro, small, and medium-sized enterprises (SMEs) are exempt from administrative charges under certain conditions.

All paediatric applications must be submitted via EMA’s IRIS platform. This secure portal supports:

• Initial Paediatric Investigation Plan (PIP)

• Modification of a PIP

• Product-Specific Waiver

• Compliance Check

• Annual Report on Paediatric Deferred Measures

• Confirmation Requests (Class Waiver Applicability, Condition vs. Indication)

• Discontinuation of Paediatric Development

Applicants are encouraged to engage with the EMA prior to submission or resubmission of applications. The Paediatric Investigation Plan (PIP) is a mandatory development plan in the EU designed to ensure that medicines are appropriately studied in children to support their authorization for pediatric use.

The PIP is a crucial document that outlines the strategy for developing medicines for the paediatric population. It details the studies to be conducted, age groups to be included, and endpoints to be assessed.

Key Aspects of the PIP:

• Initial PIP: Submitted early in the development process.

• Modification of an Agreed PIP: Allows for adjustments based on new data or changing circumstances.

• Waivers: Can be granted if the medicine is unlikely to be effective or safe in children, or if the disease/condition does not occur in the paediatric population.

• Compliance Check Request: To ensure all requirements have been met before seeking marketing authorization.

Upon receiving a submission, the EMA validates the application. The procedure then moves to assessment, where PDCO reviewers provide feedback or request additional information. If modifications are necessary, a Request for Modification (RfM) is issued. The applicant must respond via IRIS, after which a final opinion is formed.

Following PDCO’s final opinion, EMA issues a decision within 10 days. This document is critical for future marketing authorisation procedures and is published on the EMA website.

For the most up-to-date information and the full guidance document, please refer to the EMA website: Procedural advice on paediatric applications