AIFA is the competent authority in Italy for monitoring the safety of vaccines (and in general, of all authorized medicinal products) during the entire life cycle of each individual product (vaccine vigilance). This activity is essentially based on the analysis of suspected adverse reactions reports, collected through the National Pharmacovigilance Network and the European pharmacovigilance system EudraVigilance. Another database used for the surveillance of vaccines and medicines in general is the VigiBase system of the World Health Organization (WHO).
These databases are interconnected in such a way that the suspected adverse reactions reported at a national level can provide the European and global system with more extensive data than those collectable from a single population. It is worth highlighting that the activity performed at a national level is in fact integrated into a wider surveillance system at both a European level (in collaboration with the other EU National Competent Agencies) and a global level.
The analysis of suspected adverse reactions reports consists in the evaluation of all the events occurring after administration of a vaccine, in order to highlight possible associations between the administered product and the event which has occurred.
Suspected adverse reactions reported during clinical trials prior to authorization of the vaccine are considered in the assessment of the marketing authorization application: the goal is to define the benefit-risk ratio of a product. The outcome of this evaluation is fundamental not only to define the contraindications, warnings and adverse reactions to be reported in the Summary of Product Characteristics (SPC) and in the Package Leaflet (PL), but also to proactively outline all the monitoring activities of the vaccine safety to be conducted after marketing, as part of a risk management plan (RMP).
Both the product information and the RMP can be modified any time after marketing, based on the evidence inferable from further clinical studies performed after the authorization (phase IV) or from pharmacovigilance activities carried out by both the Marketing Authorization Holder and the competent regulatory authorities.
The MAHs are legally bound to regularly submit a Periodic Safety Update Report (PSUR) which shall be evaluated by the EU regulatory agencies. Regulatory authorities such as AIFA or EMA, instead, systematically monitor suspected adverse reactions reports through signal analysis activities and can at any time request a re-evaluation of the safety of a vaccine or any medicine through specific procedures at a European level.
In this way it is possible to constantly update the benefit/risk ratio of each vaccine and adopt the appropriate safety measures, whenever the post-marketing surveillance activity detects significant information on any adverse reactions already or not yet known.
The vaccine vigilance activity in Italy is carried out by a specific AIFA working group, with the participation of the ISS, the Regional Pharmacovigilance Centers, the Ministry of Health and the regional contact points on prevention.
The assessment of the correlation between an adverse event and a vaccine includes:
- collection of all the data available in the National Pharmacovigilance Network;
- integration with clinical and non-clinical data in literature;
- assessment of the probability that the vaccine may have caused the event in the individual case (causation);
- validation of the signal performed first at national level and then at European level by the EMA Pharmacovigilance Risk Assessment Committee (PRAC).
If the signal has a significant impact on the benefit-risk ratio, for example due to severity or frequency, the individual Member State raising the signal or the PRAC may decide to assess the possible risk through other procedures.
In any case, the PRAC evaluates all data available (those provided by companies or available in national, European and WHO pharmacovigilance databases) and the scientific evidence published in literature, with an aim to establish a possible correlation and to assess the clarity of such correlation.
The recommendations provided by the PRAC are also submitted to the scrutiny of other EMA committees, who may use the opinion of a specially convened committee of experts and shall finally be approved by the European Commission. Such recommendations are periodically published on the EMA website, thus made available to any stakeholder involved, and communicated by the individual national regulatory authorities.
All the safety evaluations and the related decisions able to modify the information on a vaccine are based on a precautionary principle, whereby the risk value is also attributed to factors and events not yet clearly defined.
An adverse event that is potentially or clearly related to the use of the vaccine must be reported in the product information (SPC and PL), in the sections relating to adverse reactions and/or in the sections relating to warnings or contraindications and may involve a variation of the risk management plan.
Serious or very frequent adverse events can alter the benefit/risk ratio of a vaccine so that the regulatory authority, pending further investigation, may suspend or even revoke the marketing authorization and order withdrawal from the market.