3. The Risk Management Plan (RMP)

There are two types of activities:

• Prevention: Avoid occurrence of adverse  reactions (ADR) by identifying the risk factors and recommending against the use of the medicine by patients at-risk;
• Reaction: Stop a detected ADR from worsening:

a) Provide advice to the patient on what action to take (e.g., stop taking the medicine, report to doctor/pharmacist).

b) Provide treatment to reverse the ADR. This requires:

c) This may be supported by biological markers for early detection of effect.

Risk minimisation activities can be categorised as:

a) Routine activities:

• Level 1 - routine minimisation must ensure that suitable warnings are included with all product information including careful labelling, and packaging of the medicine. These routine minimisation activities include:
• Summary of product characteristics (SmPC).
• Package labelling.
• Package leaflet.
• Pack size(s).

 b) Additional activities: go beyond level 1 activities:

• Level 2 - additional risk minimisation activities that support communication and educational activities about a risk. This needs to be focused on certain risks and presented or communicated in a useful and meaningful way. Those activities must be integrated with other activities targeting the same audiences. They may include:
• Communication from the company to healthcare professionals such as: direct healthcare professional communications; doctors’ or pharmacists’ guides; education/training programmes, e.g., a pregnancy prevention programme; website; hotline.
• Communication from healthcare professionals to patients such as: alert card, patient monitoring card, patient acknowledgement form to confirm the understanding of the risk by the patient, website.
• Specialised product packaging to enhance safe use of the medicine.
• Legal status of the product (available by prescription only, over the counter).

• Level 3 - additional risk minimisation activities in relation to access to the medicine. They include different ways of increasing constraints at all levels and place new challenges to pharmacists and distributors, such as:
• Limit prescriptions to certain doctors (e.g., those that are specifically trained or certified), pharmacists or sites (e.g., hospitals).
• Manage prescriptions through conditions of reimbursement.
• Treatment conditional on inclusion in a mandatory registry.

These activities depend on each healthcare system and require a process to monitor the effectiveness of the activities. All these activities should be adapted to local requirements, i.e., in each country.

All minimisation activities require:

• Careful design before implementation. This should include testing or feasibility phases involving all stakeholders who will be involved in the activities. This might include doctors, nurses, pharmacists, patients, patient organisations.
• Implementation plan describing how, when, where and with whom they will be implemented.
• Regular measurement of their effectiveness during implementation is mandatory.