In previous articles, we have introduced the Centralised Procedure (CP) and the Decentralised Procedure (DCP). This article will bring you relevant content about the Mutual Recognition Procedure (MRP).
The Mutual Recognition Procedure (MRP) is an important part of the EU drug registration system. It is mainly used to help drugs that have obtained marketing authorization in one EU member state to quickly gain recognition in other EU member states, thereby enabling the marketing of drugs in multiple member states. This procedure makes full use of the existing approval basis of drugs, reduces duplicate evaluations, and improves efficiency, which is of great significance for pharmaceutical companies that hope to expand their market coverage.
Applicable Scenarios of MRP
It applies to drugs that have obtained marketing authorization in at least one EU member state through the National Procedure (NP) or the Decentralised Procedure (DCP). When the drug plans to be marketed in other EU member states where it has not yet been marketed, MRP can be initiated. At this time, the member state that has approved the drug serves as the Reference Member State (RMS), and other target member states serve as the Concerned Member States (CMSs).
Core Process of MRP
1. Submission of Application: The applicant submits a mutual recognition application to all target Concerned Member States (CMSs) and notifies the Reference Member State (RMS) at the same time. The application materials need to include the marketing authorization documents in the Reference Member State, drug-related information, etc.
2. Evaluation and Feedback: The Reference Member State (RMS) provides its evaluation report and other materials on the drug to the Concerned Member States (CMSs). After receiving the materials, the Concerned Member States (CMSs) evaluate the drug and can raise questions to the Reference Member State and the applicant if they have any.
3. Reaching Consensus: If the Concerned Member States (CMSs) have no objections to the drug, they will recognize the marketing authorization of the Reference Member State, and the drug can be marketed in that member state.
4. Dispute Handling: If the Concerned Member States (CMSs) have objections to the safety, efficacy, etc. of the drug and cannot reach a consensus, they will enter the Referral Procedure.
The Referral Procedure is a procedure initiated when there are differences in the evaluation of drugs among member states during MRP or DCP that cannot be resolved through negotiation. It aims to resolve disputes through a unified mechanism and ensure the consistency of EU drug regulation.
Core Requirements for Submission of MRP in e-CTD Format
The submission of MRP (Mutual Recognition Procedure) in eCTD (Electronic Common Technical Document) format must strictly follow the *Best Practice Guide for the Use of eCTD in MRP/DCP* issued by CMDh. The core requirements cover multiple dimensions such as format principles, process specifications, and document management, as follows:
1. General Core Principles
Comprehensive Model: All eCTD documents submitted to the Reference Member State (RMS) and Concerned Member States (CMSs) shall be managed as a unified whole, using the same sequence number to ensure that all member states obtain the same version of the document. Even if some sequences only involve some member states, they must be submitted to all participants to avoid information fragmentation.
Tracking Table: Each eCTD sequence must be accompanied by a structured tracking table as an attachment to the cover letter. The tracking table must:
- Clearly identify RMS and each CMSs (distinguished by two-letter country codes)
- List CMSs in groups such as "First Wave" and "Second Wave", and arrange them in alphabetical order within each group
- Record the submission date, description and scope of each sequence (e.g., mark which member states are only information recipients with *)
- If there is a change in RMS, the record in the tracking table must be updated (e.g., the old RMS withdraws or becomes CMSs)
2. Premises for Initiating MRP and Format Requirements
Premises for Initiation: The drug must first obtain marketing authorization in at least one member state through the National Procedure (NP), and the authorization document must be in eCTD format.
Envelope Information Setting: The <procedure_type> of the eCTD envelope must be set to "mutual-recognition" and contain the MRP procedure number. If the RMS is changed later, the procedure number in the envelope and the tracking table must be updated in the next submission.
3. Sequence Management and Submission Specifications
Sequence Numbering Rules
- Sequence numbers cannot be reused unless it is a resubmission after invalid technical verification (the original number must be used)
- Joint submissions (such as general changes) must use consecutive numbers (e.g., 0001, 0002...) to ensure traceability of the life cycle
- National-specific sequences (such as amendments involving only a single CMS) still need to be numbered but only submitted to the relevant member states, and other parties do not need envelope information
Document Structure Requirements
- General documents must be placed in the shared folder, and country-specific documents (such as translations, additional data) must be placed in the country code subfolder (e.g., cc-folder) under the additional-data folder;
- National translation documents can be placed as "working documents" in the working-documents folder outside eCTD, with subfolders created by country code, following eCTD naming rules.
4. Verification and Evaluation Process
Technical Verification
- Only the MRP initiation sequence needs to undergo technical verification, based on the EU eCTD verification standards valid at the time of submission
- If the verification fails, the revised version must be submitted immediately with the same sequence number, and no new number can be added
Content Verification
- Content issues can first be communicated by email. After the verification period, all revised contents must be summarized into one eCTD sequence (the submission type is marked as "validation-response"), and the cover letter must state that "it has been submitted by email before"
- Technical verification completed during the national procedure stage does not need to be repeated, only the new sequences after the initiation of MRP need to be verified
5. Requirements for Handling Specific Scenarios
National-Specific Submissions
- Content that only affects a single member state (such as amendments to the country's labeling) can be submitted separately to that CMS, but documents in the general sequence cannot be modified (to avoid "replace" and "delete" operations affecting other member states)
- Some purely national regulatory activities (such as MAH transfer, packaging design changes) can be submitted outside eCTD, but must comply with the format requirements of the member states
Change and Lifecycle Management
- Changes, renewals, etc. must be submitted as a single sequence to all RMS and CMSs using a general application form;
- If the change only involves some specifications/dosage forms, the relevant CMSs must be clearly stated in the cover letter, and other recipients must be marked as "information recipients" with * in the tracking table
- After a change is rejected or withdrawn, the relevant sequence must still be retained in eCTD. If necessary, a consolidation sequence should be submitted to clarify the current valid version
RMS Changes
- There is no need to submit a separate eCTD sequence for RMS changes. It is only necessary to update the procedure number in the envelope and the RMS identification in the tracking table in the next submission (such as change, renewal)
- If the original RMS withdraws, the withdrawal of its marketing authorization must be submitted as an eCTD sequence, and the envelope must display the procedure number of the new RMS
6. Special Procedure Requirements
Reused Procedure (RUP): As a special form of MRP, it must follow the original eCTD lifecycle. Only the RUP initiation sequence needs technical verification, and old sequences do not need to be re-verified.
Extension Applications: They can continue the existing lifecycle or create a new lifecycle, and both methods must comply with eCTD format specifications.
The above requirements must be implemented in conjunction with the *EU Harmonised Technical eCTD Guidelines* on the EMA official website and the latest updated documents issued by HMA to ensure full compliance throughout the eCTD submission process.
In addition, the e-CTD submission channel for MRP usually needs to be through CESP (Common European Submission Portal). For specific requirements, please refer to the relevant content on the HMA official website.
BrilliantMed has rich experience in EU drug registration and can provide enterprises with professional services for the entire MRP process, including preparation of application materials, communication with regulatory authorities of various member states, dispute response, etc., to help enterprises successfully expand into the EU market.
The above is an introduction to the Mutual Recognition Procedure (MRP), and we hope it can help you understand the EU drug registration procedures.
