Medicines Healthcare Products Regulatory Agency
Legal background and scope
Regulation 78A(13) and (14) of the Human Medicines Regulations 2012, as inserted by the Human Medicines (Amendment etc.) (EUExit) Regulations 2019, requires 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 six months beginning with the day on which the trial ended.
This applies irrespective of whether or not:
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the studies are conducted in accordance with an agreed paediatric investigation plan (PIP); or
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the?MAH?intends to apply for a marketing authorisation for a paediatric indication in relation to the product.
These provisions replace Article 46 of Regulation (EC) No 1901/2006 (the Paediatric Regulation).
MHRA?will also consider the outcome of?CMDh?paediatric work-sharing procedures (PdWS) reviewed under Article 45 of Regulation (EC) No 1901/2006 (as amended). If required,?MHRA?will request updates to the product information (PI) for UK Marketing Authorisations.
1. Submission of information
In line with the regulation, the?MAH must submit a cover letter. Suggested?cover letter template within 6 months of completion (i.e. date of last visit of last subject undergoing the trial, unless otherwise justified in the protocol) of the concerned paediatric studies to the?MHRA?in eCTD format to this mailbox:?paediatricstudies@mhra.gov.uk.
The?MAH?should provide the cover letter the following information:
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TheMAHsshould state whether as a result of the paediatric study there is a need to update the product information and if there are any urgent safety of efficacy updates to the product information.
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The MAH should state whether the study(ies) have been submitted for assessment as an EU PdWS procedure under Article 46 of Reg. 1901/2006.
- If the study has been submitted to EU, the MAH should provide the final EU Assessment Report when available. Also we are asking the companies to inform us of any urgent safety or efficacy or updates identified during the EU assessment if on-going.
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The MAH should indicate 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 Human Medicines Regulations 2012, as inserted by the Human Medicines (Amendment etc.) (EU?Exit) Regulations 2019.
If this is the case, the?MAH?should provide the study title(s) with approximate date of completion. If the study(ies) relate to a UK?PIP, the?MAH?should provide the?PIP?number.
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The MAH should state whether the study(ies) have been or will be submitted in the UK as part of a variation/extension or any other application including this paediatric study. If this is the case, the?MAH?should:
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specify the UK procedure number, if available or the type of application this will be submitted under planned timings and the route of submission.
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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
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confirm that, based on the results of the study, no urgent safety update of the product information is required
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2. Initial appraisal
On receipt of the cover letter,?MHRA?will carry out an initial appraisal of whether an assessment procedure is required at this stage. One of the following may apply:
2.1. Assessment of the data is not required at this stage and?MHRA?will maintain records including justification for the decision, e.g. that a regulatory submission to vary the Marketing Authorisation is planned in the next 6 months, the MAH plans to submit the data directly as a variation or any other agreed reason(s) to defer the procedure.
If the study has been or will be submitted to the EU, the MAH must provide the final EU assessment report when available and inform us of any urgent safety or efficacy updates identified during the EU assessment if on-going. The final EU outcome (together with cover letter information) will determine further MHRA action e.g. no further action, proceed to variation.
2.2 Assessment of study data is required if, for example:
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urgent safety or urgent efficacy updates to PI.
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national licences including split GB/Northern Ireland licences.
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companys preference for a UK National type II submission
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UK specific concern for public health issues or UK specific conditions e.g. pollen immunotherapy for pollen specific to UK only.
If assessment of the study data is required:
2.2.1. Limited evaluation of the study data may be undertaken if the MAH provides robust justification that the study data are unlikely to warrant product information (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 have been reviewed in another regulatory procedure by MHRA or another competent 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 PK, 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 drugs benefit:risk ratio or be useful to prescribers and patients
- only interim results from an ongoing study are available which will be assessed later in their totality
- the study has been conducted in populations and/or diseases that are not applicable to 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 submit the study report and a short clinical overview including justification why PI changes are not necessary. A variation application will not be requested if MHRA ag