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1. Overview听听

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

and the (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 鈥渢hat part of the population consisting of persons under the age of 18 years鈥�.听听

This applies whether or not:听

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

• 迟丑别鈥�MAH鈥痠ntends to apply for a marketing authorisation or a variation/extension for a paediatric indication in relation to the product听

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. The UK paediatric submission requirements apply irrespective of product categorisation.听听

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, 迟丑别鈥�MAH must submit a (MS Word Document, 43.2 KB) to 迟丑别鈥�MHRA鈥痬ailbox at鈥�paediatricstudies@mhra.gov.uk 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:听

• 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)听

• 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听

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

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

• 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:听

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

  • if the study(ies) relate to a UK鈥�PIP, provide 迟丑别鈥�PIP鈥痭耻尘产别谤听

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

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

  • 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听

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

4.Initial appraisal听

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

4.1 Assessment of study data is not required听

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

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

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

• any other agreed reason(s) to defer the procedure听

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.听

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 鈥楲egal background and scope鈥�).听

4.2 Assessment of study data is required听

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

• there are urgent safety or urgent efficacy updates to PI听

• the MAH prefers a full UK assessment听

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

4.2.1 Limited evaluation听

If assessment of the study data is required, limited evaluation of the study data may be undertaken if 迟丑别鈥�MAH鈥痯rovides robust justification that the study data is unlikely to warrant PI changes. The鈥�MAH鈥痺ill need to state in the cover letter that one or more of the following criteria are met:听

• the same data has been reviewed in another procedure by鈥痶he MHRA鈥痮r another regulatory authority and the review has not led to鈥�PI鈥痗hanges听

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

• the drug is already licensed in the paediatric population and the study does not provide new鈥痯harmacokinetic, efficacy or safety data听

• 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鈥檚 benefit:risk ratio or be useful to prescribers or patients听

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

• 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)听

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

If one or more of the above criteria are met, 迟丑别鈥�MAH鈥痵hould also submit the study report and a short clinical overview - including justification why鈥�PI鈥痗hanges are not necessary 鈥� to paediatricstudies@mhra.gov.uk. The MHRA will not request a variation application if鈥痠t is鈥痑greed with 迟丑别鈥�MAH鈥檚 justification not to update 迟丑别鈥�PI.听

4.2.2 Full assessment听

If review of the data is required鈥�(when 迟丑别鈥�MAH鈥痯roposes a鈥�PI鈥痷pdate or when the MHRA听concludes after the initial appraisal that a full assessment is needed to robustly conclude on prospective鈥�PI鈥痷pdates), 迟丑别鈥�MHRA鈥痺ill notify 迟丑别鈥�MAH鈥痶o submit the paediatric data within 60 days as a type II variation application (under the appropriate change code with applicable fees). The鈥�MAH鈥痵hould submit the following:听

• final clinical study report听

• 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听

• 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听

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

If 迟丑别鈥�MAH鈥痠s unable to submit the Type II variation within the 60-day timeframe, they must justify the delay and propose a new submission date.听听

5. Studies remaining within EU framework听

Regarding the following scenarios where assessment is ongoing:听

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

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

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

These studies will remain within 迟丑别鈥�EU鈥痑ssessment framework and no UK equivalent procedure will be initiated unless 迟丑别鈥�MAH鈥痠ndicates 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.听

Upon finalisation of 迟丑别鈥�EU鈥痯rocedure and availability of the final assessment report, MAHs听should submit it to鈥�paediatricstudies@mhra.gov.uk. The MHRA鈥痺ill check the applicability of the outcome of 迟丑别鈥�EU鈥痯rocedure for UK products. If there are proposed changes to 迟丑别鈥�PI鈥痺hich can be directly implemented to relevant UK products, if not already submitted, 迟丑别鈥�MHRA鈥痺ill request鈥�MAHs鈥痶o submit a Type IB variation to update 迟丑别鈥�PI鈥痺ithin 60 days.听

6.Contact听

For further information, email our Customer Services Centre info@mhra.gov.uk鈥痮r call 020 3080 6000.听听

You can also email鈥�paediatricstudies@mhra.gov.uk with urgent questions.