MHRA Guidance – National assessment procedure for medicines

The MHRA offers a national assessment procedure for UK-wide marketing authorisation (MA) applications.

This new guidance for applicants is effective for applications received after 3rd April 2025, the publication date.

  • The national assessment procedure guidance applies to national MA applications for both innovative and established medicines, but the requirements, procedures and timetables differ.
  • Timetables are measured in calendar days excluding regulatory clock-stops.    

Always read the guidance on this procedure published on the MHRA website for the most up to date and complete information.

1. Innovative medicines applications

What are innovative medicines applications?

These are defined as applications for:

  • New active substances (NAS), defined as active substances that have not been authorised in a medicinal product in the UK before
  • All biological products (derived or manufactured from a living biological system) including advanced therapy medicinal products (ATMPs), vaccines and biosimilars
  • New combinations of existing active substances
  • Orphan medicinal products
  • Conditional MA or MA under exceptional circumstances
  • Line extensions of any of the above (for example, addition of strengths, pharmaceutical forms or routes of administration)
  • MA applications via Project Orbis Type A, B or C
  • MA applications via the Access Consortium New Active Substance Work Sharing Initiative (NASWSI) which are subject to a different timetable but for which the MHRA aim to make a national decision within 210 days of the start of the work-sharing procedure
Pre-submission steps for Innovative medicines applications

i) Before you apply

ii) Before submission

Notifying the MHRA and the need for a pre-submission meeting

Application typePre-submission meeting required?
National MA application for a new active substance (NAS), or a biological product including a biosimilarYes, the MHRA strongly recommend that you request a pre-submission meeting using the notification form
Applications via Project Orbis or Access Consortium work-sharing proceduresA pre-submission meeting is not always required for applications as these follow separate pre-submission procedures.

For further information you should consult Pre-submission Advice and Support.

UK paediatric requirements

MHRA clinical assessment report template

  • The MHRA encourages you to complete the factual sections of the MHRA clinical assessment report template, to facilitate a streamlined assessment procedure.
  • Guidance is provided within the template.
  • The completed template should be included in the working documents folder of your submission as a Word document. 
Submission

The MHRA operate fixed submission and assessment timetables for innovative medicines applications to facilitate consultation with the Commission on Human Medicines (CHM).  These timetables include monthly submission deadlines.

What you must submit

  • eCTD – You must submit a complete electronic Common Technical Document (eCTD) including modules 2 to 5 and a UK-specific module 1.
  • Cover letter – The cover letter should state your intention to seek orphan designation, conditional MA, or MA under exceptional circumstances, where applicable.
  • Highlight where same therapeutic indication is the subject of a line extension application and a parallel type II variation application supported by data common to both eCTD dossiers – Where the same therapeutic indication is the subject of a line extension application and a parallel type II variation application, supported by data that is common to both eCTD dossiers, you should highlight this and include the relevant PL/submission numbers in the cover letters of both applications. This will facilitate coordination of the 90-day initial assessment phases of the parallel MA and variation applications.    

MA applications via the Access Consortium NASWSI

These are subject to a different timetable (see section 2.8 on the MHRA website) for more details).

Assessment

Clock start and validation

  • The MHRA will start the clock on the next procedure start date after the validation date (see submission and assessment timetables).
  • To ensure that the procedure can start 21 days after the submission deadline, you are advised to respond promptly to validation correction requests (VCRs).
  • Validation
    • You will be notified when your application has been validated.
    • The date of the notification letter is the validation date.
    • You can also track the validation status of your application using RegulatoryConnect.
    • In the unlikely event that validation is delayed such that the date of validation is later than the target procedure start date, the MHRA will start the clock on the following procedure start date.

Initial assessment phase until Day 90

  • The MHRA will conduct an initial assessment of your application.
  • This will include an assessment of orphan designation if applicable.
  • Consulting with the CHM – The MHRA may consult with the CHM or its expert advisory groups (EAGs) for advice on quality, safety or efficacy during the initial assessment phase until Day 90.  
  • Clock stop and First RFI
    • By Day 90 (90 calendar days after the start of the procedure) the MHRA will send you the first request for information (RFI) and switch off the clock.
    • Consolidated list of questions – The RFI will be a consolidated list of questions covering all sections of the dossier, including orphan designation if applicable.
    • The MHRA may also send you relevant assessment reports and annotated product information documents.
    • Major objections – The RFI may include ‘major objections’ which, if unresolved, would preclude a marketing authorisation or orphan designation.
    • Request clarification – If you wish to discuss any RFI questions during the clock-stop period, you can request a clarification meeting with relevant members of the assessment team by contacting RIS.NA@mhra.gov.uk.

Responses assessment phase until Day 150

  • Response to first RFI within 6 months
    • You must respond to all questions raised in the first RFI within 6 months, but the MHRA encourages you to submit your complete responses as soon as possible.
    • If you do not submit a complete response within 6 months, the MHRA will notify you that it proposes to refuse your application.
    • Clock-stop extension beyond 6 months – In exceptional cases, the MHRA may agree to extend the clock-stop period beyond 6 months.
  • Submitting your complete response
    • You should submit your complete responses as an eCTD sequence.
    • You should prepare your response document using our RFI response template.
    • The response document should be provided both in PDF format in Module 1 and in Word (. docx) format in the working documents folder.
  • Submission assessment timetables – The MHRA submission and assessment timetables include monthly submission deadlines for your response to the first RFI. This is to facilitate further consultation with the CHM if required.
  • Clock restart – The MHRA will restart the clock 3 calendar days after the response submission deadline.
  • Completion of the assessment of your response to the first RFI
    • The assessment of your response to the first RFI will be completed by Day 150 (60 calendar days after the procedure restart date) and the MHRA will notify you as follows:
      • If your response has addressed all the MHRAs questions – If your response has addressed all our questions, we will notify you as soon as possible that your application is undergoing final compliance checks.
      • Minor outstanding issues and second RFI – If the MHRA identify minor outstanding issues, the MHRA will send you a second RFI letter by Day 150 (see section 2.5).
      • Major outstanding objections – If there are outstanding major objections which if unresolved would preclude a marketing authorisation or orphan designation, you will receive a CHM letter by Day 150 (see section 2.6).

Clock stop and second RFI or CHM Letter

The MHRA will stop the clock when its sends out a second RFI or CHM letter.

Final assessment phase after second RFI

  • There are no fixed submission dates for your responses to the second RFI.
  • You must submit your complete response to the second RFI within 3 months, but the MHRA encourages you to submit your responses as soon as possible.
  • If you do not submit a complete response within 3 months, the MHRA will notify you that it proposes to refuse your application.
  • In exceptional cases, the MHRA may agree to extend the clock-stop period beyond 3 months.

Clock restart after second RFI, compliance checks and MA grant

  • The MHRA will restart the clock within 3 calendar days of receiving your complete response to the second RFI as an eCTD sequence as described in section 2.4 on the MHRA website.
  • The MHRA will assess your response to the second RFI.
  • If all outstanding issues are resolved, the MHRA will conduct final compliance checks and grant your application by Day 210.  
  • When a positive decision can be made significantly earlier than Day 210, the MHRA will aim to notify you as soon as possible.

Third RFI (if necessary)

  • If necessary, the MHRA will send you a third RFI to resolve any final minor outstanding issues and switch off the clock.
  • There are no fixed submission dates for your responses to the third RFI.
  • You must submit your complete response to the third RFI within 3 months.
  • If you do not submit a complete response within 3 months, the MHRA will notify you that it proposes to refuse your application.
  • The MHRA will restart the clock within 3 days of receiving your complete response to the third RFI as an eCTD sequence as described in section 2.4.
  • Once all outstanding issues are resolved, the MHRA will conduct final compliance checks and grant your application by Day 210.

If you wish to discuss any second or third RFI questions during the clock-stop period, you can request a clarification meeting with relevant members of the assessment team by contacting RIS.NA@mhra.gov.uk.

CHM letter and representations
  • You may receive a letter from CHM instead of a second RFI by Day 150.
  • This happens if during the responses assessment phase, the MHRA consults the CHM under Paragraph 5 of Schedule 11 to the HMRs and the CHM is of the provisional opinion that it may be unable to advise the MHRA to grant the authorisation or orphan designation.
  • The reasons for the provisional opinion will be set out in the CHM letter.
  • The clock will be switched off when the CHM letter is sent.
  • You will be given the opportunity to make written or oral representations to the CHM in relation to the grounds set out in the CHM letter.
  • You will be asked to confirm to the CHM Secretariat within 28 days of receiving the letter the type of representations (written or oral) you wish to make, if any.
  • You must make representations within a further 6 months, unless you have requested and obtained a written confirmation of the extension of the time limit from the CHM Secretariat.  
  • However, the MHRA encourage you to submit your representations as soon as possible.  We will restart the clock when you make your representations.
  • Further details and instructions will be provided in the CHM letter and attached guidance notes.
  • You should submit your complete responses as an eCTD sequence.
  • You should prepare your response document using the MHRAs RFI response template.
  • The response document should be provided both in PDF format in Module 1 and in Word (.docx) format in the working documents folder.
  • Orphan drug designation will be determined at the time of MA grant.
  • If you decide to make representations in relation to orphan designation, the MHRA will defer its decision on the MA application until the representation process is complete.
  • The MHRA will consider the final advice of the CHM and proceed to grant or refuse your MA application (and orphan designation application where relevant). If we decide that your application is approvable, we may implement a third RFI round (as described in section 2.5) before we conduct final compliance checks and grant your application.  
Decision to grant or refuse your MA application

You will be notified of the MHRAs decision by a grant letter or refusal letter.

MA grant

  • The grant letter will specify any conditions of the grant, and the expiry date of the MA.
  • You should refer to Renewing Marketing Authorisations for medicines.
  • The MHRA publishes a UK Public Assessment Report (PAR) for all new MAs including conditional MAs and MAs under exceptional circumstances.
  • This is based on the MHRA assessment reports with any commercially confidential information or personal protected data removed.
  • A lay summary is included.
  • The MHRA will consult with you on the text of the final PAR before publication on the MHRA Products webpage.
  • Following authorisation of a new active substance (NAS), the MHRA will publish a press release within one week and a PAR within 30 days.
  • For all other MA types, the MHRA will publish a PAR within 60 days.  

MA refusal

  • The MHRA will only refuse an MA application after receiving the final advice of the CHM (see section 2.6), except when you have not responded to a RFI within the required timeframe.
  • The refusal letter will include the grounds for refusal, and information on how to request a review of the decision under paragraph 11 of Schedule 11 to the HMRs.
  • The MHRA will publish a refusal PAR once any appeal process is concluded, unless you withdraw the MA application before the MHRA makes its final decision.  
Access Consortium work-sharing procedures

If you are considering a national application for a new active substance or biosimilar, the MHRA encourages 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.
  • A streamlined process with an internationally coordinated review to reduce duplication/burden.
  • Joint consolidated lists of questions, capturing the assessment by all agencies.
  • Predictability due to pre-determined joint international milestones for work-sharing and peer-review between agencies.
  • Competitive timetables with a standard procedure of 180 days (excluding clock-stops).
  • Flexibility due to agency-specific Module 1 (minor differences in Module 2 to 5 may also be accepted) and separate sovereign decisions at the end of procedure.

For Access Consortium procedures:

  • a pre-submission meeting is not always required 
  • MHRA monthly fixed submission deadlines are not applicable, and
  • assessment timetables are agreed internationally in line with Access Consortium guidance.

The MHRA still aims to make a national decision within 210 days of the start of the work-sharing procedure, excluding clock-stops, or earlier if issues are resolved.

  • Interested applicants should submit an Expression of Interest form at least 3 months in advance of their anticipated submission date to each agency proposed for work-sharing.
  • For further information, or to express an interest in an Access Consortium submission, please contact access-mhra@mhra.gov.uk.
International Recognition Procedure (IRP)

Different requirements, procedures and timelines apply for MA applications via the International Recognition Procedure (IRP).

2. Established medicines applications

Before you apply

Before you apply, you should consult the following MHRA guidances where relevant:

Process changes

The MHRA has published published process changes for established medicines MA applications, effective from 1 March 2024. The process changes have been incorporated into this guidance.  

Checklists

The MHRA has developed checklists to support applicants to complete right-first-time submissions. Where relevant, the MHRA encourage you to complete these checklists and include in the working documents folder of your submission as a Word document:

UK paediatric requirements

  • UK paediatric requirements apply to established medicines applications submitted under Regulation 50 of the HMRs.
  • You should refer to Procedures for UK Paediatric Investigation Plans (PIPs).
  • When a UK PIP compliance check is required, you should submit the request at least 60 days before the planned submission date for your MA application.
Submission
  • eCTD – You must submit a complete electronic Common Technical Document (eCTD) including modules 2 to 5 and a UK-specific module 1.
  • ASMF – If your application refers to an active substance master file (ASMF) you should ensure that the file has already been submitted to MHRA with the appropriate letter of authorisation for MHRA to refer to the ASMF for the MA application to be submitted.
  • Validation
    • The MHRA aim to validate applications within 14 days.
    • However, there may be a delay if we need to send you a validation correction request (VCR).
    • You can track the validation status of your application using RegulatoryConnect.
    • When the MHRA has validated your application, it will notify you and start the clock.
Assessment

Technical competence

  • Initially the MHRA will carry out a technical completeness check of the application.
  • It will refuse the application if it determines that the data required by regulations 49 to 55 and Schedule 8 of the HMRs have not been submitted.

Scientific assessment

  • The MHRA will scientifically assess applications that are technically complete, aiming to make a final decision within 210 days excluding clock-stops.
  • If the MHRA identifies any deficiencies, you will receive a request for information (RFI) or a letter from the Commission on Human Medicines (CHM) as explained below.

Request for further information (RFI)

  • If the MHRA identifies deficiencies that should be resolved but which do not preclude a marketing authorisation, you will be sent am RFI and the clock will be switched off.
  • The RFI will be a consolidated list of questions covering all sections of the dossier.
  • The MHRA may also send you relevant assessment reports and annotated product information documents.
  • The RFI letter will include a contact email for clarifications on the questions raised.
  • Usually, you will only receive one RFI.

Response assessment

How long will you have to submit a response to an RFI?

  • You will have a maximum of 6 months to submit a response but we encourage you to submit your responses as soon as possible.
  • If you do not submit a complete response within 6 months, the MHRA will notify you that it proposes to refuse your application.
  •  In exceptional circumstances to meet public health needs and minimise the impact on patients, the MHRA may grant an extension beyond 6 months on a case-by-case basis.

How should you prepare and submit your response to an RFI?

  • You should submit your complete responses as an eCTD sequence. You should prepare your response document using our RFI response template.
  • The response document should be provided both in PDF format in Module 1 and in Word (.docx) format in the working documents folder.

Procedure following receipt of RFI response by the MHRA

  • The MHRA will restart the clock when it receives your complete response to the RFI as an eCTD sequence.
  • If your response:
    • is satisfactory, including any updated documentation to address all the questions raised in the RFI including questions on the product information, the MHRA will conduct final compliance checks and grant your application by Day 210.
    • is incomplete or does not resolve the issues raised on quality, safety, or efficacy, the MHRA will refer the application to the CHM for advice on refusal.
  • Exceptionally, where an application is approvable, the MHRA may send a second RFI to request additional information or documents before it conducts final compliance checks.
CHM consultation

About major objections

  • ‘Major objections’ are deficiencies which if unresolved would preclude a marketing authorisation.
  • If the MHRA raises any major objections, it will consult the CHM under Paragraph 5 of Schedule 11 to the HMRs.
  • If the CHM is of the provisional opinion that it may be unable to advise the MHRA to grant the authorisation, you will receive a letter from CHM.
  • The reasons for the provisional opinion will be set out in the CHM letter.
  • The clock will be switched off when the CHM letter is sent.
  • Before the CHM gives its final advice to the MHRA, you will be given the opportunity to make written or oral representations to the CHM in relation to the grounds set out in the CHM letter.
  • You will be asked to confirm to the CHM Secretariat within 28 days of receiving the letter the type of representations (written or oral) you wish to make, if any.
  • You must make representations within a further 6 months, unless you have requested and obtained a written confirmation of the extension of the time limit from the CHM Secretariat. 
  • Clock restart – The MHRA will restart the clock when you make your representations. Further details and instructions will be provided in the CHM letter and guidance notes attached to it.

How should you prepare and submit your response?

  • You should submit your complete responses as an eCTD sequence. You should prepare your response document using our RFI response template.
  • The response document should be provided both in PDF format in Module 1 and in Word (.docx) format in the working documents folder.
Decision to grant or refuse your MA application

The MHRA will consider the final advice of the CHM and proceed to grant or refuse your MA application.  

Decision to grant

  • The grant letter will specify any conditions of the grant, and the expiry date of the MA. You should refer to Renewing Marketing Authorisations for medicines.
  • The MHRA publishes a UK Public Assessment Report (PAR) for all new MAs.
  • Once the MHRA has made a decision to grant your application,you will be asked to pre-populate a template with the lay summary for the PAR.
  • Templates are available at Apply for a licence to market a medicine in the UK.
  • You should use the template that corresponds to the legal basis of your application and submit via mhraemreply@mhra.gov.uk.
  • The MHRA will complete the draft UKPAR supplied by you and publish it on the MHRA Products webpage within 60 days of grant.
  • The MHRA will consult you on the text of the final PAR before publication.

Decision to refuse

  • The MHRA will only refuse your MA application after receiving the final advice of the CHM, except when your application is technically incomplete (see section 3.3) or you have not responded to the RFI within the required timeframe (see section 3.4).
  • The refusal letter will include the grounds for refusal, and information on how to request a review of the decision under paragraph 11 of Schedule 11 to the HMRs.
  • The MHRA will publish a refusal PAR once any appeal process is concluded, unless you withdraw the MA application before the MHRA makes its final decision.   

Source: MHRA