The AFI Symposium, the Italian meeting event for experts in the pharmaceutical sector, was held in Rimini from 8 to 10 June 2022. Facing its 61st edition, its main theme was the return to the new normal. As usual, one of the sessions was dedicated to pharmacovogilance, where Dr. Cagnato of Doc Generici Srl had the opportunity to deepen the theme of risk management and educational material.

As is known, to obtain the Marketing Authorization and keep the product on the market, the pharmaceutical company must monitor the risk/benefit profile of the drug, which must be presented with a positive outcome, that is, the benefits must outweigh the risks. But this is not enough, in fact, the risks must be managed by implementing minimization measures. The process is divided into several phases:

1. Monitoring the effectiveness of data management and data collection measures
2. Identification and analysis of risks and benefits
3. Characterization of the risk/benefit ratio, which must have a positive outcome
4. Identification and planning of minimization measures, which can be routine measures or additional measures
5. Implementation of the aforementioned

Risk minimization and prevention activities must be reported in the so-called Risk Management Plan (RMP), a document that aims to:

• Identify and characterize the safety profile of the drug
• Indicate any further characterization of the safety profile
• Document the risk prevention or minimization measures
• Document post-authorization obligations

This document must be implemented for each company drug.

The identification of risk minimization measures can lead to two results: routine measures or additional measures (aMMR).

The first involves the use of tools such as the Summary of Product Characteristics (SmPC), the Patient Information Leaflet, the labeling and the drug supply regime. These must be applied to all drugs.

The second, on the other hand, are measures that are adopted as supplementary measures to the routine ones if these are not sufficient, at the local level in the country where the drug is marketed. Additional minimization measures include the distribution of educational material, such as information guides or checklists for healthcare professionals or patient diaries and warning cards.

Performing an analysis is essential to understanding the effectiveness of prevention and minimization measures. The most suitable time is between 12 and 18 months from implementation and subsequently during the drug renewal phase. Indices to be analyzed are: reduction in the frequency of the onset of reactions and their degree of severity. Patient surveys are also useful to check whether the content of the educational material has been fully understood.

The educational material is drawn up to prevent or reduce the extent of risk or improving the benefit/risk profile of the drug.

Its content complements that reported in the RCP, in the PIL and the labeling.

Its diffusion can be useful in the prescription phase by a doctor, in the dispensing phase to the patient and, finally, in the phase of use of the medicine by the patient himself.

In the drafting and evaluation of the educational material, there are four figures involved: the company, the regulatory authority, the the healthcare professional and the patient.

With the entry into force of the European legislation on pharmacovigilance, since 2012 pharmaceutical companies are required to have, for each medicinal product, a Risk Management Plan (RMP) that is clear, exhaustive and well articulated: they must be detailed any risks, any risk minimization measures, specifying the rationale, the key messages to be disclosed and the implementation and evaluation methods.

The company has the task of identifying risks and communicating risk mitigation measures. This communication is effective if:

• The target audience has been correctly identified
• The communication lines implemented are based on the target audience, such as healthcare professionals and patients
• The educational material was disseminated within a reasonable time
• The effectiveness of the measures adopted based on pharmacovigilance activities was assessed.

Furthermore, to avoid disclosing misaligned information or inconsistent messages leading to confusion, MAHs of the same AS are invited by Good Pharmacovigilance Practices (GVP) to share and compare their educational material.

Given that the Risk Management Plan is a document drawn up by the company, various Authorities intervene upon its approval:

• Pharmacovigilance Risk Assessment Committee (PRAC): is responsible for assessing the RMP and analyzing the implemented measures
• European Medicines Agency (EMA): publishes summaries of RMPs to disseminate information
• Co-ordination Group for Mutual Recognition and Decentralized Procedures – Human (CMDh): updates the list of risks in the previously approved document
• Italian Medicin Agency (AIFA)’s Risk Management Measures Office, evaluates and approves the educational material in Italy, if required by the RMP.

The healthcare professional must be properly informed about any risks associated with the administration of a drug. It is his task too, to inform the patient and invite him to read the package leaflet and any other informative brochures.

The most common problems faced by companies are:

1. Identification of risks and their alignment between drugs with the same AS
2. Publication of summaries of RMPs at the European level, which are often not complete
3. Evaluation of the correct dissemination and understanding of the educational material by patients
4. Identification of the method of evaluating the effectiveness of risk minimization measures and consequent decision to implement new measures.

Dr. Cagnato hopes for the future some actions aimed at improving the RMP can be implemented such as the promotion of the importance of knowledge of the MMRs contents, the dissemination of more widespread information to healthcare professionals, greater proactivity by the pharmaceutical companies, the harmonization of RMPs among the various MAHs and the publication of educational materials on all institutional websites for more immediate identification of risks by healthcare professionals and patients.