GovWire

1. Overview

The rolling review is a route for marketing authorisation applications (MAA), where an applicant for a marketing authorisation submits modules of the ?eCTD? dossier incrementally for pre-assessment by the?MHRA?rather than as part of a consolidated full dossier submission.

The rolling review is intended to streamline the development of novel medicines by offering periodic enhanced regulatory interaction and advice to reduce the risk of failure at the final phase and may be integrated with the?Target Development Profile (TDP)?to provide a clearer pathway for development of innovative medicines.

Until the Windsor Framework is implemented on 1 January 2025 [1], Rolling Review applications can only be submitted for applications to Great Britain. From that date the MHRA will license new active substances and biosimilars UK-wide and the rolling review process will be available for UK-wide applications.

2. Eligibility

Rolling review can be used for a full dossier new active substance (NAS) in the UK or for a similar biological medicinal product (a biosimilar). Supporting data requirements for a new active substance are unchanged from those set out in regulation 50(5) of the Human Medicines Regulations, or for a biosimilar in regulations 53A (for Great Britain) or 53B (for UK) of the Human Medicines Regulations.

3. How to apply

The process is a modular approach to submission and evaluation. The quality, non-clinical and clinical data may be submitted separately or jointly, depending on individual circumstances and/or data availability, in the format of common technical modules ?CTD? modules 3-5.

Applicants should refer to guidance on?Procedures for UK Paediatric Investigation Plans (PIPs)?and the UK compliance check (CC) should be completed 60 days before the intended submission.

Applicants intending to use the rolling review you should request a pre-submission meeting to discuss the product, its intended target populations and the data in each module to be submitted.

To apply for a pre-submission meeting, a completed application should be sent to?AcceleratedandRollingReview@mhra.gov.uk.

Applications, including the first module(s) to be assessed, should be submitted through our portal, MHRA?Submissions. Read our guidance about using the?MHRA?submission portal.

4. Fees

Fees will be payable for each phase of assessment.

Find out more about the fees we charge in the guidance:?MHRA ?fees.

Find out more about how to pay your fees in our guidance:?Make a payment to the?MHRA.

5. Assessment

5.1 Pre-assessment of modules

The assessment of the first module will start following validation of the application. The assessment cycle will be completed within 60 days. Following each assessment cycle, a Module Assessment Summary (MAS) will be issued by Day 60. The MAS will offer the applicant opportunities to update the module which should be included in the final (marketing authorisation application) phase. The same timeline above will be applied for each modular assessment.

The assessment process may include consultation with the?CHM ?and/or therapy area experts during the pre-assessment process.

5.2 Before submission

Applicants should refer to guidance on Procedures for UK Paediatric Investigation Plans (PIPs) and the UK compliance check (CC) should be completed 60 days before the intended submission.

5.3 Pre-submission meeting

A pre-submission meeting with the? MHRA? around 90 days in advance of the intended submission for the final marketing authorisation application is recommended. At the meeting applicants may wish to provide a short summary of the dossier, as well as to raise any special issues such as requests for consideration for orphan MA, conditional MA or MA under exceptional circumstances.

The pre-submission meeting may offer the opportunity to enhance joint discussion with the National Institute for Health and Care Excellence (NICE) Health Technology Assessment (HTA) evaluation process. The ?MHRA ?will operate a fixed submission date system to facilitate consultation with the Commission on Human Medicines and will publish a set of submission dates to facilitate planning the submissions and coordinate with appropriate meeting dates of? CHM.

5.4 Validation of applications (MAAs)

A valid application/dossier should include submission of any unassessed modules or data, which may include the clinical module, UK specific ?CTD? module 1, consisting of an appropriate Risk Management Plan (RMP) and/or orphan designation application (if applicable).

The?SmPC/PIL ?may be submitted as word documents in the working documents folder. There is an option to put the UK specific?SmPC / PIL / labelling text / mock-ups in the UK specific folder which is available within the? eCTD ?structure.

The assessment clock will begin after validation of the application.

5.5 Final phase assessment

The final phase should be completed within 100 days in two stages as 60 + 40 days with an intervening clock off period. If required, a letter requesting further information (RFI) may be issued by Day 60 with the clock stopped. Applicants will have the opportunity to discuss any issues identified with the ?MHRA? within 30 days.

Once the?RFI?response is received, the clock will resume on Day 61, and the final decision on approvability will be reached by Day 100. The orphan status will be determined at the time of grant of the marketing authorisation.

6. Appeals

If the?MHRA?proposes to refuse to grant the MA based on advice from?CHM, there is an opportunity for the applicant to request a review of the decision. The procedure for such a review is set out in Schedule 5 and paragraph 11 of Schedule 11 to the Human Medicines Regulations 2012.

The?MHRA?decision letter will detail the appeal process and timelines. If orphan status is not agreed and the applicant company wishes to appeal this decision, the grant of a marketing authorisation will only be possible when the appeal process is completed.

7. Publication

The granting of a marketing authorisation will lead to the publication of a Public Assessment Report for the product.

8. Further information

For further information, please email our Customer Services Centre atRIS.NA@mhra.gov.uk or call 020 3080 6000

[1] Subject to the UK providing written guarantees to the European Commission as provided for in Article 8 of EU Regulation 2023/1182 and following the entry into force and application procedure provided for in Article 14