How the rolling review process for marketing authorisation applications will work, and how to apply.
The rolling review is a new route for marketing authorisation applications (MAA), where an applicant for a marketing authorisation submits increments of the eCTD dossier 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.
It may be used for a new active substance (NAS) in the UK, Great Britain (England, Scotland and Wales), or Northern Ireland. This is in accordance with regulation 50(5) of the Human Medicines Regulations, or for a similar biological medicinal product in Great Britain in accordance with regulations 53A of the Human Medicines Regulations.
Products eligible for the rolling review
MAAs for any NAS based on a ‘full dossier’, including biological products, are eligible for the rolling review. Similar biological applications, i.e., biosimilar products, are also eligible.
Submission of the application
Companies who wish to enter the rolling review should request a pre-submission meeting to discuss the product, its intended target populations and the data in each module to be submitted. Companies may specify future MAA designated for UK, Great Britain (England, Scotland and Wales) only, or Northern Ireland only.
To apply for a pre-submission meeting, a completed application should be forwarded to the AcceleratedandRollingReview@mhra.gov.uk. Following receipt of the request, the MHRA will arrange a mutually acceptable date for the meeting. There is no fee payable for the pre-submission meeting.
Applications, including the first module(s) to be assessed, should be submitted via the MHRA Portal.
Each phase of assessment (for quality, non-clinical and clinical modules) will attract a fee payable as set out in Regulation 28(A) of Schedule 2 to the Medicines (Products for Human Use) (Fees) Regulations 2016.
Process and sequence
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, as appropriate).
Pre-assessment of modules
Following the process by the Information Processing Unit (IPU), the assessment of the first module will start from Day 0. 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 phase. The same timeline above will be applied to other module assessments.
The assessment process may include consultation with the CHM and/or therapy area experts (specialty expert groups) during the pre-assessment process.
Final phase (for marketing authorisation application)
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.
A pre-submission meeting with the MHRA around 90 days in advance of the intended submission for the final phase 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.
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), UK CC 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.
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 EAG/CHM will be consulted again with the final decision on approvability reached by Day 100. The orphan status will be determined at the time of grant of the marketing authorisation.
Appealing a decision to refuse
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 review is set out in Schedule 5, and paragraph 11 of Schedule 11, to the Human Medicines Regulations.
The MHRA decision letter will detail the appeal process and timelines. If orphan status is not agreed and company may wish to appeal this decision, the grant of a marketing authorisation will only be possible when the appeal process is completed.
Grant of a Great Britain marketing authorisation will lead to the publication of a Great Britain Public Assessment Report for the product.