GovWire

1. Overview

This guidance explains the process for applicants applying for a paediatric investigation plan (PIP), modification, waiver or compliance check. It explains UK paediatric requirements including those related to applications made through the International Recognition Procedure (IRP) and includes changes related to the Windsor Framework arrangements for medicines, which come into force on 1 January 2025.

You should read this guidance in conjunction with the guidance on the format and content of paediatric investigation plans and related applications in the UK. The format and content guidance provides definitions of terminology used in this guidance.

2. General approach to UK paediatric investigation plans

The legal requirements for United Kingdom (UK) paediatric medicines are set out in the Human Medicines Regulations 2012 (HMRs), as amended.

This guidance addresses the common scenarios for paediatric submissions to the MHRA. A case-by-case discussion should always be considered for paediatric submissions that do not meet the criteria listed in this guidance.

All MHRA regulatory submissions which trigger the UKs paediatric requirements must have an agreed or adopted UK PIP (and relevant compliance checks) or full product specific waiver or confirmation of a class waiver in place. This applies irrespective of regulatory route (direct national, IRP, Access or Project Orbis).

Applicants must include the latest MHRA decision documents (and MHRA compliance check outcomes, if applicable) in the MHRA regulatory submission which triggers paediatric requirements to ensure validation of the marketing authorisation (MA) or variation application.

Agreed paediatric plans from other regulatory authorities cannot be used to validate an MHRA regulatory application. This is regardless of whether a paediatric study/investigation plan has been agreed by another regulator in the context of an IRP, Access or Project Orbis application.

All requests for agreements of UK PIPs, full product specific waivers, confirmation of class waivers, modifications and compliance checks for agreed or adopted UK PIPs must be submitted to the MHRA through the dedicated PIP submissions portal.

Further information on the format and submission process for PIPs and related procedures via the MHRA submissions portal is available in separate, published user reference guides in the portal and via published guidance. Email applications for these procedures will not be accepted.

Applicants should include information that is relevant and specific to the UK, particularly with respect to any areas of unmet therapeutic need that the product intends to cover (see section 8).

EU PIPs which became UK PIPs on 1 January 2021 will be referred to as adopted UK PIPs in this guidance.

New PIP submissions after 1 January 2021 that have been assessed and agreed by the MHRA will be referred to as agreed UK PIPs in this guidance.

3. The Windsor Framework

Until 31 December 2024

Where applicable, UK paediatric requirements apply to Great Britain-only MA applications and variations, whereas UK and EU paediatric requirements apply to UK-wide MA applications and variations.

After 1 January 2025

The MHRA will license medicines across the whole of the UK from 1 January 2025.

Medicines that were previously within the scope of the EUs centralised procedure will be authorised under UK-wide MAs and no longer be limited in territorial scope as GB MAs. These products will be designated in line with definitions in UK law as category 1?. Medicines outside this scope (which can already be authorised as UK-wide MAs), will be designated as category 2. Each MA application and existing authorised product will be assigned by the MHRA to one or other category.

Where applicable, UK paediatric requirements will apply to MA applications and variations for category 1 products whereas UK and EU paediatric requirements will continue to apply to MA applications and variations for category 2 products. Detailed information on UK-wide licensing and product categorisation is available in the UK-wide licensing of human medicines guidance.

The MHRA expects that the majority of regulatory submissions triggering paediatric requirements will be for category 1 products. Guidance on specific paediatric requirements for category 2 products is provided in section 9.

4. PIP submissions

4.1 Applications subject to paediatric requirements

Since 1 January 2021, the requirement for certain applications to include the results of a PIP are set out in Regulation 50A of the HMRs.

The following MHRA regulatory applications are subject to PIP requirements, regardless of route (direct national, IRP, Access or Project Orbis).

Initial marketing authorisation applications:

• Regulation 50: new active substance, or

• Regulation 50: known active substance, or

• Regulation 55: fixed combination products, or

• Regulation 50E: paediatric use marketing authorisation applications (PUMAs)

Line extensions (changes to the active substance(s) including the salt/ester, isomer or biological active substance, or changes to strength, pharmaceutical form or route of administration):

• where a supplementary protection certificate (SPC) or a qualifying patent applies, and

• application is for new indications, new pharmaceutical forms or new routes of administration

Variations:

• to add new indications where an SPC or a qualifying patent applies

• related to PIP implementation

4.2 Timing of UK PIP submissions

According to Regulation 50B (3) of the HMRs, applications for the agreement of a 