Guidance
European Commission (EC) Decision Reliance Procedure
How to apply for marketing authorisation via this new procedure.
For a period of two years from 1 January 2021, when determining an application for a Great Britain Marketing Authorisations (MA), the MHRA may rely on a decision taken by the European Commission (EC) on the approval of a new MA in the centralised procedure.
Great Britain refers to England, Scotland and Wales.
This route – the EC Decision Reliance Procedure (ECDRP) – is available to MAs approved via the centralised procedure.
The intended operation of the ECDRP is submission of the Marketing Authorisation Application (MAA) to the MHRA immediately on receipt of a positive Committee for Medicinal Products for Human Use (CHMP) opinion, although applications can be submitted any time after the approval of a European Union Marketing Authorisation.
The MHRA aims to determine the Great Britain MA as soon as possible after EC approval. A delay in submission may affect the delivery of a decision within the 67-day timeline.
How to apply
Prior to submission the Applicant should email Reference.Data@mhra.gov.uk if this is the company’s first application, and then must apply for a PLGB number through MHRA Submissions or by emailing PLNumberAllocation@mhra.gov.uk.
Letter of intent
To facilitate scheduling, prior to receiving a positive CHMP opinion, companies should submit a ‘letter of intent to submit an ECDRP’ to the MHRA at least 4 weeks before submission of the ECDRP MAA. This should be submitted to the ECDRP mailbox once a positive CHMP opinion is anticipated, for example after receiving confirmation that no major concerns remain.
The letter should state when the company intends to submit the application and should be accompanied by all iterations of the CHMP assessment reports that have been received to date.
The letter should also state whether the company intends to apply for an orphan designation in Great Britain. Fees will be payable only after the dossier is received and not during this pre-procedure stage.
MAA Submission
On receipt of the positive CHMP opinion, or as soon as possible after this date, the ECDRP MAA should be submitted to the MHRA as one electronic Common Technical Document sequence through MHRA Submissions.
The submission should include the entire dossier as reviewed by the CHMP (and approved by the EC if the EC decision has already been received), including the full responses to CHMP questions. If the entire dossier has already been submitted to the MHRA as Northern Ireland, and no changes are required for the ECDRP MAA dossier, the dossier need not be submitted for the ECDRP MAA.
The Working Documents Folder should include:
- all iterations of the CHMP assessment reports and the CHMP opinion for the initial MAA and any subsequent variations,
- the proposed product information in Microsoft Word format.
Orphan designation
If an orphan designation is sought, the Great Britain Orphan Drug Designation Application Form should be submitted in module 1.2 of the eCTD. Email IPUenquiries@mhra.gov.uk if you have any questions about submitting your application.
Paediatric requirements
For submissions which will trigger paediatric requirements, applicants should ensure the latest European Union and/or Great Britain-PIP / waiver opinion / decision or class waiver decision is included in the dossier. If the application has been subject to a European Union or Great Britain compliance check the outcome documents should be included in the dossier.
The applicant should also indicate any parallel, ongoing or previous applications containing paediatric data relevant for the full PIP compliance verification (if applicable). An overview table of the PIP results, indicating in which application(s) they were/are going to be submitted, status of the application(s), as well as their location in the present application must be included.
Cover letter
The cover letter accompanying the application should:
- clearly state the regulatory route as ECDRP to ensure appropriate handling, including the relevant procedure number for the centralised MAA.
- include a declaration of conformity of the Great Britain application with the dossier that received a positive opinion from the CHMP (and was approved by the EC if the EC decision has already been received), including approved variations.
- include a declaration that all iterations of the CHMP assessment reports and End of Procedure documents have been submitted. These assessment reports should also be listed.
- include a declaration that the proposed product information is identical to that which received a positive opinion from the CHMP (and was approved by the EC if the EC decision has already been received), and that the product information in Microsoft Word format has been included with the submission.
- confirm that the Great Britain Orphan Drug Designation Application Form has been submitted in module 1.2 of the eCTD, if an orphan designation is sought
- indicate whether paediatric requirements will be triggered, and if so, that the paediatric information is included in the dossier. The applicant should indicate if this application has been subject to a European Union or Great Britain-PIP compliance check and confirm whether any PIP studies were due to initiate or complete since compliance verification.
Fees
The submission will attract a fee.
Assessment procedure
When a submission is made within 5 days of CHMP positive opinion, the date of CHMP positive opinion will be designated Day 0 of the ECDRP, and the MHRA will aim to determine the Great Britain MA as soon as possible after EC approval, and by Day 67 at the latest provided that EC decision has been received.
If the application is submitted more than 5 days after the CHMP positive opinion, Day 0 of the ECDRP will be the date of MAA validation, and determination may be delayed.
All applications will be reviewed to ensure they comply with Great Britain regulatory requirements, including those related to Great Britain Reference Medicinal Products, product name, labelling, patient information legibility, supply status, controlled drug scheduling where necessary, and paediatric and orphan medicine requirements, where relevant.
Any concerns relating to the approvability in Great Britain will be raised with the Applicant at the earliest opportunity. If it is found during the assessment phase that the dossier is incomplete or assessment reports have been omitted, this will be raised as a Point for Clarification, and may cause a delay to the timetable.
The Applicant is responsible for confirming the EC decision to the MHRA; the EC decision letter should be forwarded to the ECDRP mailbox on the day that it is received.
For orphan medicines, the Applicant is also responsible for confirming the COMP (Committee on Orphan Medicinal Products) decision using the ECDRP mailbox. Any delay in providing these confirmations will impact the timing of the Great Britain application determination.
Any issues identified during assessment will be communicated to the applicant by Day 46 and should be resolvable within the 67-day timetable without clock-stop.
If Major Objections are raised
If Major Objections are identified or substantial amendments to the product information are necessary, the timetable will move to the standard National Procedure timetable. It is anticipated that this will be necessary only on rare occasions.
Decentralised and mutual recognition reliance procedure for marketing authorisations
How to apply for the decentralised and mutual recognition reliance procedure (MRDCRP).
The MHRA has the power to have regard to Marketing Authorisations (MAs) approved in European Union Member States (or Iceland, Liechtenstein, Norway) through decentralised and mutual recognition procedures with a view to granting the MA in the UK or Great Britain (England, Scotland and Wales)
This power is laid out in Chapter 4 of 2001/83/EC as amended.
This route – the MRDC Reliance Procedure (MRDCRP) – can be used to apply for a UK MA [PL] or for a Great Britain MA [PLGB].
The intention is that acceptable MAs should be granted within 67 days of MAA validation. The MRDCRP is not available to products with MAs in European Union Member States granted only through National Procedures.
This document will refer to European Union Member States (although the text applies also to Iceland, Liechtenstein and Norway).
How to apply
An Applicant should first email Reference.Data@mhra.gov.uk if this is the company’s first application, and then must apply for a PL (or PLGB) number through MHRA Submissions or by emailing PLNumberAllocation@mhra.gov.uk.
The entire dossier as approved for marketing in the EUMember States, including the full company responses to Reference Member State (RMS)/Concerned Member States (CMS) questions, should be submitted to the MHRA as one electronic Common Technical Document sequence through MHRA Submissions.
The Working Documents Folder should include:
- all iterations of the RMS assessment reports and End of Procedure documents for the initial MAA and subsequent variations
- the proposed product information in Microsoft Word format
- the MA grant letter as approved in the RMS.
Orphan designation
If an orphan designation is sought, the Great Britain Orphan Drug Designation Application Form should be submitted in module 1.2 of the eCTD. Email IPUenquiries@mhra.gov.uk if you have any questions about submitting your application.
Paediatric requirements
For submissions which will trigger paediatric requirements, applicants should ensure the latest European Union and/or Great Britain-PIP/waiver opinion/decision or class waiver decision is included in the dossier.
If the application has been subject to a European Union or Great Britain compliance check the outcome documents should be included in the dossier. The applicant should also indicate any parallel, ongoing or previous applications containing paediatric data relevant for the full PIP compliance verification (if applicable). An overview table of the PIP results, indicating in which application(s) they were/are going to be submitted, status of the application(s), as well as their location in the present application must be included.
Cover letter
The cover letter accompanying the application should:
- clearly state the regulatory route as MRDCRP to ensure appropriate handling, including the relevant MR/DC procedure number.
- include a declaration of conformity of the UK/Great Britain application with the dossier approved for marketing in European Union Member States, including approved variations.
- include a declaration that all iterations of the RMS assessment reports and End of Procedure documents have been submitted. These assessment reports should also be listed.
- include a declaration that the proposed product information is in line with that approved in the European Union Member States, and that the product information in Microsoft Word format has been included with the submission. The applicant should list all differences between the proposed product information and that approved in the European Union Member States
- confirm that the Great Britain Orphan Drug Designation Application Form has been submitted in module 1.2 of the eCTD, if an orphan designation is sought
- Indicate whether paediatric requirements will be triggered, and if so, that the paediatric information is included in the dossier. The applicant should indicate if this application has been subject to a European Union or Great Britain-PIP compliance check and confirm whether any PIP studies were due to initiate or complete since compliance verification.
If it is found during the assessment phase that the dossier is incomplete or assessment reports have been omitted, this will be raised as a Point for Clarification, and may cause a delay to the 67-day timetable.
Fees
The submission will attract a fee.
Assessment procedure
All applications will be assessed to ensure they comply with UK regulatory requirements, including those related to:
- Great Britain Reference Medicinal Products
- product name
- labelling
- patient information legibility
- supply status
- controlled drug scheduling where necessary
- paediatric and orphan medicine requirements, where relevant
The first round of assessment should be completed by Day 42, at which point the MA will be granted if no concerns are raised.
Any points will be sent as a Request for Further Information (RFI) and the clock will be stopped for up to 28 days to give the Applicant the opportunity to respond. If there are no outstanding points at Day 65 the MA will be granted within 67 days of MAA validation.
If Major Objections are raised
If Major Objections are identified, substantial amendments to the product information are necessary, or other concerns remain outstanding at Day 65, the timetable will move to the standard National Procedure timetable.