The lifecycle of vaccines, from development to post-marketing vigilance
The word “vaccine” is now very much recurring in the daily news; it is important, then, to understand the steps that characterise the development of this particular type of medicines until they get into the market.
We heard many times in these days, on the TV and social media, that for the development of a vaccine, the microorganism responsible for the disease must be well known. Starting from in vitro studies, the qualitative and quantitative composition of the vaccine can be defined and investigations can be started on animal models. Such investigations help to define the mechanism of action and the toxicological profile. The most effective formulations are thus selected to be investigated in humans.
However, human clinical trials are far from being a final step: there can be up to three clinical trial phases in humans, with a progressive increase of the patients treated. Moreover, during these phases other factors are defined: the vaccine efficacy, any adverse reaction and whether a primary immunisation is sufficient or if a booster is necessary. The possibility of administering the vaccine together with other vaccines is also investigated.
Phase 3 clinical trials are particularly important because they confirm the efficacy and safety of the vaccine, and are in fact those involving the highest number of subjects.
Once the trials are concluded, the relevant data are submitted to the competent authorities that will assess them from both a technical, scientific and regulatory point of view. Only in the case of a positive risk-benefit profile for humans, the vaccine assessment procedure will end with its approval.
For vaccines as well as for drugs, national or community procedures are in force: the competent authority would be therefore the European Medicine Agency (EMA) in case of a centralised procedure, or those of more Member States (in case of mutual recognition or decentralised procedures), or of a single State for national procedures. Only following the release of the relevant marketing authorisation, vaccines can be marketed.
The vaccine process, however, does not end here. After its marketing, post-authorisation studies are started to control its efficacy and safety under real use conditions. Further information can also be obtained: this includes its cost-benefit profile compared to other products or its safety in use on special populations or in the presence of specific diseases.
The results of these phase 4 trials could completely change the outcome of any previous assessment up to the marketing discontinuation of the vaccine. In fact, as reminded by the Italian Medicine Agency, vaccines are intended to be administered to healthy subjects for preventive purposes, and maximum efficacy and high superiority of its benefit against any possible risk are expected.
Finally, as vaccines have been a topic under discussion for many years, it is worth to remind some quality aspects, covering their development up to manufacturing and marketing.
All vaccine development studies should comply with the Good Clinical Practice (GCP) standards, as provided for internationally, as its manufacturing process should meet the requirements of the Good Manufacturing Practice (GMP), regularly controlled by specific inspections of the relevant authorities.
The suitability of the manufacturing and the possible presence of contaminants developed during the manufacturing process are checked twice on each single batch before its delivery to vaccine centres.
Moreover, further controls are carried out by the manufacturer, by accredited laboratories and by other independent bodies during the whole manufacturing cycle of the vaccine and before its arrival on the market: this is the state control that is carried out on each batch in all European states.
The usual pharmacovigilance monitoring – applying to all medicinal products – adds to these controls as well as the annual random control of the composition by the High Health Institute (ISS).
Vaccines are therefore safe and much controlled products, that can prevent the development and spreading of infective diseases, contributing to public health and increasing health safety standards.
