Before a new vaccine is approved for release on the market, a rigorous regulatory procedure to assess quality, efficacy and safety must be undertaken.
1. Marketing authorisation
Vaccines have to obtain a marketing authorisation before being sold. This marketing authorisation is granted after an evaluation of the risk-benefit ratio of the vaccine based on a dossier which presents the data collected during the product development and clinical trials. The evaluation relates to a number of product properties such as quality, safety and efficacy. Compliance with good practices in the areas of manufacturing and clinical or laboratory testing is also verified by regulatory agencies prior to approval of a marketing authorisation.
Furthermore, during vaccine development, the manufacturer must evaluate the needs of the paediatric population and, if appropriate, propose a paediatric clinical development plan to the European Medicines Agency (EMA). The manufacturer will have to comply with the approved plan. Compliance with the plan approved details will be verified at the time of the submission of the Marketing Authorisation application. Non compliance would result in the refusal of the application.
2. Registration or licensing
Registration or licensing of pharmaceutical products in Europe can be done by different procedures:
The assessment of products by the Centralised Procedure is undertaken by the European Medicines Agency (EMA). A single application is sent to the EMA and evaluated by its Committee for Medicinal Products for Human Use (CHMP). The final decision is made by the European Commission that issues a marketing authorisation valid throughout the EU, Iceland, Liechtenstein and Norway.
This procedure is mandatory for certain products such as medicinal products manufactured using biotechnological processes and can be used for products presenting an EU-wide public health interest such as pandemic vaccines.
Mutual Recognition Procedure (MRP)
This procedure is applicable to the majority of conventional medicinal products. It is a two-stage procedure based on:
- the evaluation and approval of a registration dossier by a “Reference Member State” and
- the recognition of the Reference Member State approval by other European countries, the “Concerned Member States”.
The applicants can choose the reference Member State and the concerned Member States. This procedure results in a collection of national marketing authorisations.
More recently, the European institutions have proposed an alternative to the MRP. It is called the Decentralised Procedure. This is a collaborative procedure led by a Reference Member State. It is essentially aimed to new products and also results in a collection of national licenses.
This pathway is reserved for products that are only licensed in one single country.
3. Quality assessment
Once a marketing authorisation is obtained, each batch of vaccines must still be assessed for quality before release for use. This is done by both the manufacturer and an official European control laboratory. The activities of these laboratories are coordinated by the European Pharmacopoeia Secretariat within the European Directorate for Quality of Medicines (EDQM). The European Pharmacopoeia Secretariat also has the responsibility for developing legally binding monographs to ensure appropriate quality control and harmonised quality standards across manufacturers and ultimately for the persons getting vaccinated.
National regulatory agencies also control the organisation of vaccine manufacturers and their manufacturing processes by regular inspections.
In addition, all vaccines and pharmaceuticals are monitored after release onto the market for adverse events. This surveillance allows both to refine the safety profile established during the product development and to detect rare events that may not have been apparent during the clinical development. This surveillance function is strengthened at European level with the establishment of the European Centre for Disease Prevention and Control (ECDC).
5. Additional requirements
Finally, vaccines will have to meet additional requirements after-licensing:
- Post-licensure commitments / follow-up measures, e.g. stability studies, further confirmatory safety trials or trials in populations that have not been studied yet
- Variations to the original marketing authorisation in order to introduce minor, moderate or major changes to the authorised details of the product
- License renewals, which under European legislations have to be submitted five years after approval