EMA Risk Management Plan

Companies are required to submit a risk-management plan (RMP) to the European Medicines Agency (EMA) when applying for a marketing authorization.

Risk management plan include detail information on:

- a medicine's safety profile;

- how its risks will be prevented or minimized in patients;

-plans for studies and other activities to gain more knowledge about the safety and efficacy of the medicine;

- measuring the effectiveness of risk-minimization measures.

For medicines that do not have an RMP, one may be required with any application involving a significant change to the marketing authorization.

In addition, for nationally authorized medicinal products, any national competent authority (NCA) in the EU can request an RMP whenever there is a concern about a risk affecting the benefit-risk balance of a medicine.

RMPs are continually modified and updated throughout the lifetime of the medicine as new information becomes available.

Companies need to submit an updated risk management plan:

- at the request of EMA or an NCA;

- whenever the risk-management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit-risk profile or as a result of an important pharmacovigilance or risk-minimization milestone being reached.

When justified by risk, the competent authority can also specify a date for submission of the next RMP as a condition of the marketing authorization in exceptional cases.

RMPs can only be submitted at the same time as the periodic safety update report (PSUR) if the change in the RMP comes as a consequence of the PSUR.

Marketing authorization applicants for COVID19 vaccines should follow EMA's guidance on preparing RMPs for COVID-19 vaccines, together with the guidance in this section and Good pharmacovigilance practices.

The guidance reflects special safety monitoring measures for COVID-19 vaccines by providing considerations and requirements for several sections of the RMP.

Since July 2022, EMA has been publishing RMPs (main body and annexes 4 and 6) of centrally authorized products that:

- contain a new active substance

- are of particular public interest

For all the other centrally authorized products, EMA publishes summaries of RMPs.

The aim of publishing these documents is to increase transparency on the safety review process of a medicine or active substance. The RMP or RMP summaries are available on each medicine page. Alternatively, a list of all RMP summaries is available.

EMA Risk Assessment

The following general points need to be considered when writing or reviewing an RMP for a medicinal product. 

Part II: Safety specification

• Have all appropriate parts of the safety specification been included?
• Have all appropriate data been reviewed when compiling the safety specification?
• If parts of the target population have not been studied, have appropriate safety concerns in relation to potential risks and missing information been included?
• Have limitations in the safety database (e.g. related to the size of the study population, study inclusion and exclusion criteria) been considered and what are the implications of such limitations on the safety profile of the medicinal product? 
• For generic or hybrid applications, have all safety concerns from the latest version of the RMP for the reference medicinal product or from a list of safety concerns published on the CMDh website been included in the safety specification? If not, has appropriate justification been provided and has the applicant proposed a list of safety concerns? If no information on the safety profile of the reference medicinal product is available (no RMP or no CMDh list for the substance), has the safety profile been drafted considering all available relevant information (e.g. public assessment documents for the reference medicinal product, literature, applicant’s own trial data)?

Part III: Pharmacovigilance plan

• Are all safety concerns from the safety specification covered in the pharmacovigilance plan?
• Are routine pharmacovigilance activities adequate or are additional pharmacovigilance activities necessary?
• Are the activities in the pharmacovigilance plan clearly defined, described and suitable for identifying or characterizing risks or providing missing information?
• Are the safety studies that have been imposed by a competent authority as conditions clearly identified?
• If there are safety concerns derived from medication errors, does the RMP include appropriate proposals to monitor the correct use of the product?
• Are the proposed additional studies necessary, feasible, non-promotional and able to provide the required further characterization of the risk(s) and address the scientific questions?
• Are timelines and milestones appropriate and feasible for the proposed actions, including those for the submission of results?

Part IV: Plans for post-authorization efficacy studies 

• Have all post-authorization safety studies (PAES), either as conditions of the marketing authorization or as specific obligations, been included?

Part V: Risk minimization measures

• Are routine risk minimization measures sufficient or is there a need identified for additional risk minimization activities? 
• Have additional risk minimisation activities been suggested and, if so, are these sufficiently justified and risk-proportionate? Is implementation feasible in all Member States? 
• Have criteria for effectiveness of additional risk minimisation activities been defined a priori?
• Are the methods for evaluating the effectiveness of risk minimization activities well described and appropriate?

Part VI: Summary of the risk management plan

• Is it a true representation of the RMP?
• Have the facts been presented appropriately without any elements of promotional nature?