Completed paediatric studies: submission, processing and assessment
Source: gov.uk (2025-02-13)

Guidance on the submission, processing and assessment of all completed paediatric studies sponsored by marketing authorisation holders (MAHs).

1. Overview

This guidance explains the scope and legal basis for the initial and full submission requirements, as well as the processing and assessment of all completed paediatric studies sponsored by marketing authorisation holders (MAHs).

2. Legal background and scope

Regulation 78A(13) and (14) of the Human Medicines Regulations 2012, as amended by the Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (https://www.legislation.gov.uk/uksi/2019/775/part/5/made?view=plain) and the Human Medicines (Amendments relating to the Windsor Framework) Regulations 2024 (https://www.legislation.gov.uk/uksi/2024/832/made) (HMRs), require that holders of a UK marketing authorisation who sponsor a study which involves use in the paediatric population in respect of the medicinal product to which that authorisation relates must submit to the Medicines and Healthcare products Regulatory Agency (MHRA) results of the study within the period of 6 months beginning with the day on which the trial ended. The paediatric population is defined in the HMRs as “that part of the population consisting of persons under the age of 18 years”.

This applies whether or not:

the studies are conducted in accordance with an agreed paediatric investigation plan (PIP)

the MAH intends to apply for a marketing authorisation or a variation/extension for a paediatric indication in relation to the product

From 1 January 2025, the MHRA is making decisions on the licensing of all medicines across the UK, and medicinal products will be designated Category 1 or Category 2. See UK-wide licensing for human medicines (https://www.gov.uk/government/publications/uk-wide-licensing-for-human-medicines#full-publication-update-history). The UK paediatric submission requirements apply irrespective of product categorisation.

This guidance addresses the common scenarios for paediatric submissions to the MHRA, regardless of whether the product is Category 1 or Category 2. A case-by-case discussion should always be considered for paediatric submissions that do not meet the criteria listed in this guidance.

3. Submitting information

In line with the regulation, the MAH must submit a Cover letter (download template) (https://assets.publishing.service.gov.uk/media/67adf73e63d7f4cceef9e160/Cover_letter_for_completed_paediatric_studies__1_.docx) (MS Word Document, 43.2 KB) to the MHRA mailbox at xxx@xxx.xx (mailto:xxx@xxx.xx) within 6 months of completion of the concerned paediatric studies (that is, the date of the last visit of the last subject undergoing the trial, unless otherwise justified in the protocol).

In the cover letter, the MAH should state:

whether there is a need to update the product information as a result of the paediatric study and if there are any urgent safety or efficacy updates to the product information (PI)

whether the study(ies) have been submitted for assessment by a non-UK regulator such as the EU procedure under Article 46 of Regulation (EC) No 1901/2006

if so, provide a final assessment report from the non-UK regulator as soon as available

if the non-UK regulator assessment is ongoing, inform the MHRA of any urgent safety or efficacy updates identified during the review

whether the study(ies) are linked to other paediatric studies which have been or will be the subject of other submissions under Regulation 78A of the HMRs, if so:

provide the study title(s) with approximate date of completion

if the study(ies) relate to a UK PIP, provide the PIP number

whether the study(ies) have been or will be submitted in the UK as part of a marketing authorisation or variation/extension, if so:

specify the UK product licence (PL) number and the type of application this will be submitted under, planned timings and the route of submission

confirm that the application will be submitted within the next 6 months, if not, provide justification for the delay including an estimated date of submission

confirm that, based on the results of the study, no urgent safety update of the product information is required

4.Initial appraisal

On receipt of the cover letter, the MHRA will carry out an initial appraisal of whether an assessment procedure is required at this stage. One of the following may apply:

4.1 Assessment of study data is not required

Assessment of the study data is not required at this stage. The MHRA will maintain records including justification for the decision, for example:

a regulatory submission is planned in the next 6 months to the MHRA where the study data will be included for review

the MAH plans to submit the data directly as a variation to the MHRA

any other agreed reason(s) to defer the procedure

If the study has been submitted or will be submitted to the EU then the MAH must provide the final Article 46 EU assessment report as soon as possible when it becomes available.

If the assessment is ongoing, the MAH must inform the MHRA of any urgent safety or efficacy updates identified during the assessment. The final EU Article 46 outcome (together with cover letter information) will determine further MHRA action, for example, no further action, proceed to variation.

The initial appraisal step does not lead to change(s) to the product information (PI). If changes are required to the PI, the company must submit an appropriate MHRA regulatory submission (refer to section on ‘Legal background and scope’).

4.2 Assessment of study data is required

Assessment of the study data is required if, for example:

there are urgent safety or urgent efficacy updates to PI

the MAH prefers a full UK assessment

there is UK-specific concern for public health issues or UK-specific conditions such as pollen immunotherapy for pollen specific to UK only

4.2.1 Limited evaluation

If assessment of the study data is required, limited evaluation of the study data may be undertaken if the MAH provides robust justification that the study data is unlikely to warrant PI changes. The MAH will need to state in the cover letter that one or more of the following criteria are met:

the same data has been reviewed in another procedure by the MHRA or another regulatory authority and the review has not led to PI changes

the study was conducted mainly in adult patients with limited paediatric patients included

the drug is already licensed in the paediatric population and the study does not provide new pharmacokinetic, efficacy or safety data

the study, due to its design, limited number of paediatric patients, discontinuation or other reason does not allow drawing conclusions on efficacy or safety that would impact on the drug’s benefit:risk ratio or be useful to prescribers or patients

only interim results from an ongoing study are available - they will be assessed later in their totality

the study has been conducted in populations and/or diseases that are not applicable to the UK (for example, hay fever to specific seasonal pollen found in non-UK countries)

other justification as to why a detailed assessment is not required at this stage

If one or more of the above criteria are met, the MAH should also submit the study report and a short clinical overview - including justification why PI changes are not necessary – to xxx@xxx.xx (mailto:xxx@xxx.xx). The MHRA will not request a variation application if it is agreed with the MAH’s justification not to update the PI.

4.2.2 Full assessment

If review of the data is required (when the MAH proposes a PI update or when the MHRA concludes after the initial appraisal that a full assessment is needed to robustly conclude on prospective PI updates), the MHRA will notify the MAH to submit the paediatric data within 60 days as a type II variation application (under the appropriate change code with applicable fees). The MAH should submit the following:

final clinical study report

a short clinical overview clarifying the context of the data, including information on the pharmaceutical formulation used in the study, the existence of a suitable paediatric formulation and if relevant, conditions for an extemporaneous formulation

a summary of the Product Characteristics or Patient Leaflet (SmPC/PL) proposal to update the paediatric information, or when none is considered required, justification that changes are not necessary

or a paediatric study that is part of a development program including a PIP, a line listing of all relevant studies

If the MAH is unable to submit the Type II variation within the 60-day timeframe, they must justify the delay and propose a new submission date.

5. Studies remaining within EU framework

Regarding the following scenarios where assessment is ongoing:

results of paediatric studies that have been submitted to the EMA or the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) under Article 46 of Regulation (EC) No 1901/2006 before 1 January 2021, or

Paediatric Work Sharing Procedure (PdWS) for Mutual Recognition and Decentralised procedures – submitted before 1 January 2024, or

paediatric studies submitted under Article 45 of Regulation (EC) No 1901/2006 work sharing procedure

These studies will remain within the EU assessment framework and no UK equivalent procedure will be initiated unless the MAH indicates that an urgent safety and efficacy update of the PI is required. However, the cover letter still needs to be submitted to the MHRA for these studies.

Upon finalisation of the EU procedure and availability of the final assessment report, MAHs should submit it to xxx@xxx.xx (mailto:xxx@xxx.xx). The MHRA will check the applicability of the outcome of the EU procedure for UK products. If there are proposed changes to the PI which can be directly implemented to relevant UK products, if not already submitted, the MHRA will request MAHs to submit a Type IB variation to update the PI within 60 days.

6.Contact

For further information, email our Customer Services Centre xxx@xxx.xx (mailto:xxx@xxx.xx) or call xx-xxxx-xxxx.

You can also email xxx@xxx.xx (mailto:xxx@xxx.xx) with urgent questions.