Risk management plan

A RMP should be submitted as part of the dossier of all new drug applications including generics and national applications and is evaluated by regulatory authorities before a medicine can be authorised. An RMP can also be requested by regulatory authorities for already authorised products that do not have an RMP in place yet when there is a concern about a risk affecting the benefit-risk balance. The RMP should include information on:

• a medicine's safety profile describing the important identified and potential risks
• plans for studies and other activities to gain more knowledge about the safety and efficacy of the medicinal product (pharmacovigilance activities)
• how its risks will be prevented or minimised in patients (risk minimisation measures)
• measuring the effectiveness of risk-minimisation measures.

Detailed guidance on the content, format and submission of RMPs is available on the EMA website and in the Guideline on good pharmacovigilance practices (GVP) - Module V – Risk management systems.

The template for the EU-RMP can be found on the EMA website: EMA guidance on the format of the risk management plan in the European Union.

RMPs are continually modified and updated throughout the lifetime of the medicine as new information becomes available. Marketing authorisation holders need to submit an updated RMP:

• At the request of the EMA, MEB or other national competent authority
• Whenever the RMP 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 minimisation milestone being reached.

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

Submitting a risk management plan

In order to expedite the processing of submissions, please include the following in the header of the accompanying letter – where applicable, and preferably in the following order:

• All product names your letter applies to, and all associated RVG or EU marketing authorisation numbers for products authorised via the centralised procedure
• Case number (if available)
• Date of the letter you are responding to
• Type of procedure (National/MRP, DCP/Centralised) with – where applicable – the relevant procedure number
• Contact person’s e-mail address
• A brief description of the topic of your letter
• Whether and when a RMP update has taken place:
  • If an update has taken place, include a brief description of implemented changes
  • If no updates have occurred: Indicate that no updates have been performed since <date of the last EU RMP submission>

Enclose the following:

• The RMP with visible changes (track changes)
• The final version of the RMP

The accompanying letter for an electronic dossier must also include the following data:

• The number of CD(s) or DVD(s) for the complete dossier
• A declaration that the contents of the electronically submitted information is identical to the corresponding hard copy documents
• A declaration that the submission has been scanned using an up-to-date virus scanner
• A declaration that the application has been drafted in accordance with the ICH Granularity Document
• An overview of the CD(s) or DVD(s) contents.

Risk minimisation measures

Risk minimisation measures are interventions intended to prevent or reduce the occurrence of adverse reactions associated with the exposure to a medicine, or to reduce their severity or impact on the patient should adverse reactions occur.

Risk minimisation measures can consist of routine risk minimisation or additional risk minimisation measures. 

Routine risk minimisation is applicable to all medicinal products, and involves the use of the summary of product characteristics (SmPC); the patient information leaflet; the labelling; the pack size and design; the legal status of supply of the product.

For some risks routine risk minimisation measures are not sufficient and additional measures are required. The additional risk minimisation measures for a medicinal product are specified as a requirement in the Risk Management Plan (RMP) or Annex II of the Conditions of Marketing Authorisation. A variety of tools are currently available for additional risk minimisation such as educational materials, controlled access programmes or a pregnancy prevention programme. This field is continuously developing, and new tools are likely to be developed in the future. Technology advances, such as interactive web-based tools may gain prominence in the future in addition to the paper-based materials.

Before additional risk minimisation measures can be implemented in the Netherlands the Dutch proposal must be assessed at national level by the MEB. Only approved risk minimisation measures can be distributed in the Netherlands. The MEB offers specific guidance for marketing authorisation holders on the additional risk minimisation measures intended for the Netherlands.

The MEB is obliged to assess national implementations / translations of risk minimisation measures determined on the European level. Only medicinal products that have nationally approved additional risk minimisation measures may be marketed.

When there are approved additional risk minimisation measures, the relevant materials will be delivered by the marketing authorisation holder to the healthcare provider. Patients receive the materials from the healthcare provider, if applicable. More information about the specific additional risk minimisation measures can be requested from the marketing authorisation holder of the medicinal producted.