MHRA guidance on 150-day assessment for national applications for medicines

Last updated: 16 June 2023

See updates at the end of the post.

The UK MHRA has published guidance on 150-day assessment for national applications for medicines from 1 January 2021.

The 150-day assessment for national applications

The MHRA offers a 150-day assessment timeline for all high-quality marketing authorisation applications (MAAs), aiming at accelerating the availability of medicines for patients in the UK.

Under this process, the MHRA will evaluate the application for one of the following marketing authorisations and reach its opinion on approvability within 150 days of submission of a valid application:

  • UK marketing authorisation
  • Great Britain (England, Wales and Scotland) marketing authorisation
  • Northern Ireland marketing authorisation
Access consortium worksharing procedures

If you are considering a National Application for any of the following:

  • a new active substance,
  • a biosimilar product, or
  • a new indication application

then the MHRA invites you to consider submission via an Access Consortium work-sharing procedure. These procedures allow simultaneous submission to the UK, Australia, Canada, Singapore and/or Switzerland. Potential advantages to companies include:

  • Simultaneous submission for access to multiple markets.
  • Streamlined process: Internationally coordinated review to reduce duplication/burden. Joint, consolidated lists of questions, capturing the assessment of all agencies.
  • Predictability: Work-sharing and peer-review between agencies, with pre-determined joint international milestones.
  • Competitive timetables: Standard procedure of 180 days (excluding stop-clocks).
  • Flexibility: Module 1 will be different between jurisdictions, while minor differences in Module 2-5 may also be accepted. Separate sovereign decisions at end of procedure
  • Opportunity to make a contribution to innovation in the area of regulation.
Where should applications for national applications be submitted?

Applications should be submitted via the MHRA Submission Portal. The appropriate national fee will apply.

What will the MA application process depend upon?

The MA application process will depend on whether the medicinal product contains:

  • New active substances or biosimilar products
  • Existing active substances
What is the application process for each of the above?
1. New active substances and biosimilar products

The steps are:

i) Pre-submission:
Complete the PIP compliance check

Refer to the guidance on  Procedures for UK Paediatric Investigation Plans (PIPs) and complete the UK compliance check (CC) 60 days before the intended submission date.

Contact the MHRA:

When contacting the MHRA, the letter should include the following details:

  • Intended date of submission
  • whether the MAA is to be submitted to UK, Great Britain (England, Scotland and Wales) only, or Northern Ireland only
What if the medicinal product is presented or used with a device component?

For such products, refer to guidance on regulating medical devices.

Pre-submission meeting

The pre-submission meeting applies to new active substances and biosimilar applications. should be requested at least 90 days before the intended submission date.

At the meeting applicants may wish to:

  • provide a short summary of the dossier to share their intentions and
  • verify the new active substance status.

They may want to raise any specific issues such as requests for:

  • consideration for orphan MA
  • conditional MA
  • MA under exceptional circumstance

The meeting:

  • will also offer opportunity to discuss the arrangements for UK Compliance Check on PIPs.
  • may offer the opportunity to enhance joint discussion with 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 dates to facilitate planning the submissions to coordinate with appropriate meeting dates of CHM.

ii) Submission and validation of applications

A valid, full application should be submitted to the MHRA for evaluation. It should include:

  • CTD modules 2-5
  • a UK specific CTD module 1, consisting of an appropriate Risk Management Plan (RMP), UK PIP CC and/or compliance with UK Orphan Medicines requirements, when applicable.

The accompanying cover letter should detail the intention to seek orphan status or MA under exceptional circumstances as 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.

What about Applications that refer to an Active Substance Master File?
  • Ensure that the file (including the restricted part) has already been submitted to MHRA
  • Provide a suitable letter of access authorising MHRA to make reference to the confidential information in the restricted part of the ASMF.

The assessment timetable will begin after validation of the application.

iii) Assessment process and expert advice
  • The assessment process includes consultation with the Commission on Human Medicines (CHM) on fixed dates each month.
  • The submission slots will be linked to the dates of CHM meetings.
  • The MHRA may additionally wish to seek advice/input from therapy area experts (specialty expert groups) during the assessment process.
The phases of the assessment process
  • The assessment process will run in two phases totalling 150 days
  • There will be an intervening clock-off period between phase I and phase II, if required.
Assessment phase I
  • This phase will be completed 80 days after the clock starts.
  • Issues arising/requiring clarification from the initial assessment will be raised with the applicant as a letter requesting further information (RFI) and should be addressed within the clock off period of 60 days.
  • Requests for extension of the clock off period for up to another 60 days may be granted exceptionally.
  • Applicants may contact the assessment team for discussing issues raised in the RFI letter.
  • Assessment in phase-I will also address eligibility for grant of orphan status.
Assessment phase II
  • This will commence on receipt of the applicant’s responses fro phase I.
  • Applicants are recommended to contact the MHRA Assessment Team in advance of the intended date of submission of response to align with CHM meetings.
  • Based on the assessment, the MHRA will provide a decision on approvability of the product by day 150.
iv) 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.

The orphan status will be determined at the time of MA grant. If orphan status is not agreed and the company wishes to appeal this decision, the grant of a marketing authorisation will only be possible when the appeal process is completed.

v) Publication

Conclusion of the assessment will lead to the publication of a UK Public Assessment Report for the product.

2. Existing active substances

For applications made only to Great Britain, refer to:

i) Submission and validation of applications

A valid application/dossier should include:

  • CTD modules 2-5, as appropriate
  • a UK specific CTD module-1, and
  • an appropriate Risk Management Plan.

Applications that refer to an ASMF should ensure that the file has already been submitted to MHRA or included in the submission.

The assessment timetable will begin after validation of the application.

ii) Assessment process and expert advice
  • The assessment process will run in two phases totalling 150 days with an intervening clock-off period between phase I and phase II, if required.
Assessment phase I
  • This phase will be completed within 80 days after clock start.
  • Concerns arising from the initial assessment will be raised with the applicant as a letter requesting further information (RFI).
  • MHRA will seek advice from CHM and/or therapy area experts (specialty expert groups) during the assessment process, as required.
  • All concerns must be fully addressed in the clock off period of 60 days.
  • Requests for extension of the clock off for up to another 60 days may be granted exceptionally
  • Applicants may contact the assessment team for discussing issues raised in the RFI letter.
Assessment phase II
  • Phase II assessment will begin on receipt of the applicant’s responses from phase I.
  • Based on the assessment, the MHRA will provide an opinion on approvability of the product by day 150, and if positive, will grant the MA.
iii) 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.
iv) Publication

Conclusion of the assessment will lead to the publication of a UK Public Assessment Report for the product.

Source: MHRA Website

Updates
DateUpdate
16 Jun 2023Heading Access consortium worksharing procedures added with relevant content in line with MHRA update of 15 Jun 2023
28 October 2022Updated section 1. New active substances and biosimilar products, sub-section Pre-submission meeting, to add the two sentences at the beginning of the section. Source: MHRA
23 August 2021 MHRA has published updated Commission on Human Medicines (CHM) dates for national marketing authorisation applications containing new active substances.