V.B.3. Overview of the format and content of the risk management plan (RMP)
The RMP consists of seven parts. The submitted RMP shall follow the RMP template [IR Annex I]. Part II of the RMP – Safety specification is subdivided into modules [IR Annex I], so the content can be tailored to the specifics of the medicinal product. RMP part II modules generally follow the section titles in the safety specification of ICH-E2E (see GVP Annex IV). The modular structure aims to facilitate the update of the RMP; in addition, in specific circumstances certain RMP modules may have reduced content requirements (see V.C.1.1.).
However, the RMP document is expected to be submitted as one single document including all modules and annexes, as relevant. An overview of the parts and modules of the RMP is provided below in Table V.1. [IR Annex I]:
Table V.1. Overview of the RMP parts and modules
| Part I | Product(s) overview |
| Part II | Safety specification |
| Module SI | Epidemiology of the indication(s) and target population(s) |
| Module SII | Non-clinical part of the safety specification |
| Module SIII | Clinical trial exposure |
| Module SIV | Populations not studied in clinical trials |
| Module SV | Post-authorisation experience |
| Module SVI | Additional EU requirements for the safety specification |
| Module SVII | Identified and potential risks |
| Module SVIII | Summary of the safety concerns |
| Part III | Pharmacovigilance plan (including post-authorisation safety studies) |
| Part IV | Plans for post-authorisation efficacy studies |
| Part V | Risk minimisation measures (including evaluation of the effectiveness of risk minimisation activities) |
| Part VI | Summary of the risk management plan |
| Part VII | Annexes |
The amount of information, particularly in RMP part II, should be proportionate to the identified risk and the potential risk, and will depend on the type of medicinal product, its risks, and where it is situated in its life cycle (by reference to DIR Art 8(3)).
Article 14(2) of Regulation (EC) No 1394/2007 provides for a specific framework for RMP for advanced therapy medicinal products (ATMP). The marketing authorisation applicants/holders should adapt the risk management plans of ATMP, considering and discussing the anticipated post-authorisation followup needs, focusing on particularities of these medicinal products. The specific RMP content requirements for ATMP should be discussed with the competent authority before the submission. Further guidance on the safety and efficacy follow-up and risk management requirements for ATMP is provided on the Agency’s website (2) .
It is recommended, where appropriate, that the RMP document includes all relevant medicinal products from the same applicant/marketing authorisation holder containing the same active substance(s) (i.e. the RMP is an active substance-based document) [IR Art 30(2)].
Information in the RMP should be provided in enough detail whilst avoiding unnecessary text that distracts from the key issues to be considered for risk management of the product. However, the safety specifications in the RMP should not be a duplication of data submitted elsewhere in the dossier, unless the sections are intended to be common modules with other documents such as the PSUR. Where applicable, the information in the RMP should provide an integrated overview/discussion focusing on the most important risks that have been identified or are anticipated based on pre-clinical, clinical and post-marketing data presented in other modules of the eCTD. Any data included in the RMP should be consistent with other sections of the dossier. Links or references to relevant sections of the non-clinical and clinical overviews and summaries should be included in the RMP.
For new RMP submissions for nationally authorised products with limited safety data in the dossier, the RMP may contain the relevant safety data and discussion, to support the risk identification discussion.
To aid consistency between the information provided in the dossier and the RMP, Table V.2. indicates where information from the eCTD is likely to be discussed in the RMP. The eCTD data refers to the submission containing the RMP (e.g. initial marketing authorisation applications and major variations) or to historical data already included in the dossier with previous submissions.
In the context of a centralised procedure, the RMP should be submitted as part of an eCTD submission; however, for non-centralised procedures the RMP submission might still be part of a CTD submission. eCTD data/submissions in this Module should be read as eCTD or CTD data/submission, corresponding to the type of submission to the competent authority.
Table V.2. Mapping between RMP modules and information in eCTD
| RMP Module | eCTD |
| Part I Product(s) overview | Module 2.3 Quality overall summary Module 3 Quality |
| Module SI Epidemiology of the indication(s) and target population(s) | Module 2.5 Clinical overview |
| Module SII Non-clinical part of the safety specification | Module 2.4 Non-clinical overview Module 2.6 Non-clinical written and tabulated summaries Module 4 Non-clinical study reports |
| Module SIII Clinical trial exposure | Module 2.7 Clinical summary Module 5 Clinical Study reports |
| Module SIV Populations not studied in clinical trials | Module 2.5 Clinical overview |
| Module SV Post-authorisation experience | Module 2.5 Clinical overview |
| Module SVI “Additional EU requirements for the safety specification” | Data not presented elsewhere in eCTD |
| Module SVII Identified and potential risks | Module 2.5 Clinical overview (including benefit-risk conclusion) Module 2.7 Clinical summary (SPC) |
| Module SVIII Summary of the safety concerns | Module 2.5 Clinical overview Module 2.7 Clinical summary |
| Part III Pharmacovigilance plan (including postauthorisation safety studies) | Module 2.5 Clinical overview Module 2.7 Clinical summary |
| Part IV Plans for post-authorisation efficacy studies | Module 2.5 Clinical overview Module 2.7 Clinical summary |
| Part V Risk minimisation measures (including evaluation of the effectiveness of risk minimisation activities) | Module 2.5 Clinical overview Module 2.7 Clinical summary |
Only key literature referenced in the RMP should be included in RMP annex 7. This should be in the format of electronic links or references if already included elsewhere in eCTD (see V.B.10.).The description of the parts and modules of an RMP in V.B.4. provides guidance on the main topics to be addressed within each specific area. However, some sections may not be relevant to all medicinal products and there may be additional topics that need to be included but are not mentioned in this guidance. The RMP is part of the scientific dossier of a product and as such should be scientifically based and should not include any element of a promotional nature.The preliminary section of the RMP should include the following administrative information about the RMP document:
- data lock point of the current RMP;
- sign off date and the version number of the RMP;
- list of all parts and modules. For RMP updates, modules version number and date of approval (opinion date) should be tabulated in this section. High level comment on the rationale for creating the update should be included for significant changes to each module;
- The evidence of oversight from the qualified person for pharmacovigilance (QPPV) is not needed for versions submitted for assessment. The QPPV’s actual signature or the evidence that the RMP was reviewed and approved by the QPPV should be included in the finalised approved version of the document; for eCTD submissions this would be the RMP with the last eCTD sequence of the procedure (e.g. closing sequence). The evidence of QPPV oversight can take the form of a statement that the RMP has been reviewed and approved by the marketing authorisation holder/applicant’s QPPV and that the electronic signature is on file.