If review of the data is required (when the MAH proposes a PI update or when MHRA concludes after the initial appraisal, that a full assessment is needed to robustly conclude on prospective PI updates), MHRA will notify the MAH to submit the paediatric data within 60 days as a type II variation application (change code C.I.13 - complex type II variations fees will be applicable). The MAH should submit the following:

specify the UK procedure number, if available or the type of application this will be submitted under planned timings and the route of submission. If the MAH holds other paediatric studies for the same active substance falling under the scope of EU Article 45 of Regulation (EC) No 1901/2006 which have not yet been assessed by a competent authority, these should be submitted along with a clinical overview clarifying the context of the data. the same data have been reviewed in another regulatory procedure by MHRA or another competent authority and the review has not led to PI changesIf 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. 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) the drug is already licensed in the paediatric population and the study does not provide new PK, efficacy or safety data 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 HP Inc UK Limited is authorised and regulated by the Financial Conduct Authority (FCA FRN 973346) and acts as a credit intermediary and not a lender, offering credit products provided by a limited number of finance providers. Such credit products may not be suitable for everyone. Borrowing more than you can afford or paying late may negatively impact your financial status and ability to obtain credit.

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. 3. Studies remaining within EU framework 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. 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.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 agrees with the MAH’s justification not to update the PI. If the proposed PI changes are directly applicable to UK products, if not already submitted, the MHRA will send a request to the UK MAHs to submit a type IB variation within 60 days. 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: The Micro Fine 78A Toner provides highly accurate placement and control to ensure consistently sharp text and smooth grayscales while HP’s Smart Print Technology makes automatic adjustments to optimize print quality and enhance reliability.

If proposed PI changes are not directly applicable to the UK products, the MHRA may adapt the recommendations and subsequently send requests to UK MAHs for type IB variation, where the UK adapted recommendations will be provided, within 60 days. 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. 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. In accordance with the Microsoft Silicon Support Policy, HP does not support or provide drivers for Windows 8 or Windows 7 on products configured with Intel or AMD 7th generation and forward processor UK specific concern for public health issues or UK specific conditions e.g. pollen immunotherapy for pollen specific to UK only.For a paediatric study that is part of a development program including a PIP, a line listing of all relevant studies. Upon finalisation of the EU procedure and availability of the final assessment report, MAHs should submit this to [email protected]. only interim results from an ongoing study are available which will be assessed later in their totality

Regulation 78A(13) and (14) of the Human Medicines Regulations 2012, as inserted by the Human Medicines (Amendment etc.) ( EU Exit) 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. HP calculations based on ENERGY STAR® normalised TEC data comparing the HP LaserJet 300/400 series and 500 series monochrome printers introduced in spring 2019. HP 58/59/76/77A/X compared to HP 26A/X, and HP 89A/X/Y compared to HP 87A/X. A Summary of Product Characteristics/ Patient Leaflet ( SmPC/PL) proposal to update the paediatric information, or when none is considered required, justification that changes are not necessary. If the results of a paediatric study have been submitted to EMA or CMDh under Article 46 of Regulation (EC) 1901/2006 before 1 January 2021 or a decentralised procedure the process will remain within the EU assessment framework and no UK equivalent procedure will be initiated unless the MAH indicates that an urgent safety update of the product information ( PI) is required. In line with the regulation, the MAH must submit a cover letter. Suggested cover letter template Suggested cover letter template ( MS Word Document, 41 KB) 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: [email protected] 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 and patients 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: 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