1. The Risk Management Plan (RMP)

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Health authorities have increasingly adopted new regulations mandating companies to proactively manage the risk for all their medicines. Risk management planning and related activities may differ from one country/region to another in order to allow adaptation to each healthcare infrastructure, regulatory requirements and legal framework. In the EU marketing authorisation applicants are required to submit risk management plans (RMPs). These should include information on a medicine's safety profile and plans for pharmacovigilance activities designed to gain greater knowledge about the safety and efficacy of the medicine and also explain how risks will be minimised in patients and how those efforts will be measured.

The primary aim and focus of the RMP remains that of appropriate risk management planning throughout a medicinal product’s life cycle. It is designed to optimise the benefit-risk balance over time. For this purpose, it documents the risk management system considered necessary to identify, characterise and minimise a medicine’s important risks. The RMP contains:

1.  the ‘safety specification’: the characterisation of the safety profile of the medicine, concentrating on important identified and important potential risks and missing information, and also on which safety concerns need to be managed proactively or further studied;

2.  the ‘pharmacovigilance plan’: the planning of pharmacovigilance activities to characterise and quantify clinically relevant risks, and to identify new adverse reactions; it contains both routine and additional pharmacovigilance activities;

3.  the ‘risk minimisation plan’: the planning and implementation of risk minimisation measures, including the evaluation of the effectiveness of these activities.

The risk management plan evolves during the life-cycle of a medicine as knowledge regarding a medicine’s safety profile increases over time. The RMP is a dynamic document that should be updated throughout the life cycle of the product(s). This includes the addition of safety concerns where required, but also, as the safety profile is further characterised, the removal or reclassification of safety concerns.

An RMP or an update, as applicable, may need to be submitted to the Regulatory Authorities at any time during a product’s life-cycle,  As stated above, it is required for all new marketing authorisation (MA) applications. In addition, situations where an RMP or RMP update will normally be expected include:

  • Application involving a significant change to an existing MA:
    • New dosage form.
    • New route of administration.
    • New manufacturing process of a biotechnologically-derived product.
  • Significant change in indication: this is a change of authorised indication(s) of a medicine where the new  target population differs materially from the one for which the medicine was previously authorised. This includes (but is not limited to): a new disease area, a new age group (e.g., paediatric indication).

  • At the request of EMA or a national competent authority (NCA) when there is a concern about a risk affecting the benefit-risk balance.
  • At the time of the renewal of the MA if the product has an existing RMP.
  • An updated RMP should always be submitted if there is a significant change to the benefit-risk balance of one or more medicines included in the RMP.