The company marketing a product may set up post-authorisation clinical trials for purposes of obtaining information on use in particular patient populations (e.g. the elderly, or liver-impaired) or for obtaining other data on the way that the product is used.

Post-authorisation studies that are set up specifically to evaluate product safety are referred to in as “post-authorisation safety studies” or PASS. These studies are described in the risk management plan at the time of application for marketing authorisation and become post-marketing commitments for the company. They may also be required to be set up, if regulatory authorities consider that there is a need for additional safety information after marketing.

After approval in the EU, the company holding the marketing authorisation is required by regulation to continue monitoring safety. It must enter reports of suspected ADRs on a validated safety database and review the data for signals of possible new adverse reactions or other concerns. Any change to the balance of benefits and risks must be reported to the regulatory authorities, in addition to the reporting of individual cases and periodic safety update reports.

For products with national marketing authorisation in the EU, the regulatory authority in the Member State where the product is marketed has responsibility for reviewing safety by examining the safety reports that it receives from the company and directly from health professionals working in that country. The national regulatory authority also reviews PSURs from companies. It enters the case reports it receives onto the Eudravigilance database, held by EMEA.

For mutual recognition and centrally authorised products, the responsibility for monitoring safety rests with the EU regulatory authority that acted as Rapporteur or Reference Member State. However, each national regulatory authority will still receive local reports of adverse reactions from companies and health professionals and must enter these onto the Eudravigilance database. The EMEA acts as a coordinating body for the safety activities for centrally authorised and mutual recognition products, but the safety reviews are performed by assessors in the Member State regulatory authorities.

The Committee on Medicinal Products for Human use (CHMP) – comprised of representatives of each of the EU regulatory authorities – is involved at intervals with review of the PSURs for centrally authorised products and with safety issues arising post-marketing. These are channelled through its Pharmacovigilance Working Party (PhVWP), which comprises pharmacovigilance representatives from each Member State.

Legislation provides mechanisms for referral of important safety issues potentially affecting public health throughout Europe to the CHMP by the PhVWP. There are complex procedures for examining the benefit-risk balance of products if there are major safety concerns, and for making recommendations to the European Commission for suspending or revoking marketing authorisation.

There are two main strands to the assessment of safety of marketed medicines: spontaneous reporting and post-authorisation studies. However, it should be pointed out that company-sponsored research may be continuing in countries  where the product is not yet marketed, in order to obtain marketing authorisation there. Safety information from those studies is required by regulation to be reported to the competent authorities where the drug is marketed. In the same way, studies may be set up looking at new indications for the marketed drug, or use in new populations, or with different dosage forms. All of these may generate data on adverse reactions that is relevant to the marketed product and which is legally required to be forwarded by the sponsor company to the competent regulatory authorities.