A post-authorisation safety study (PASS) is any study relating to an authorised medicinal product conducted with the aim of identifying, characterising or quantifying a safety hazard, confirming the safety profile of the medicinal product, or of measuring the effectiveness of risk management measures [DIR 2001/83/EC Art 1(15)].

In order for a PASS study to be conducted in one or more countries in the European Union (EU), approval of the study protocol by the national competent authority or the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) is required. Once the protocol is approved, the PASS study can start.

PASS studies can either be interventional (clinical trials) or non-interventional, and can be conducted in one or more EU countries.

Interventional PASS fall under Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use and Law 249/2022 for the approval of Emergency Government Ordinance no. 29/2022 on establishing the institutional framework and measures necessary for the implementation of Regulation (EU) No 536/2014, and are managed by the Clinical Trials Unit of NAMMDR.

The non-interventional PASS fall under the European pharmacovigilance legislation, namely Directive 2010/84/EU, COMMISSION IMPLEMENTING REGULATION (EU) No 520/2012, Regulation (EU) No 1027/2012 and at national level under Law no. 95/2006 on healthcare reform, as republished, Chapter X Pharmacovigilance. The non-interventional PASS are managed by the Pharmacovigilance and Risk Management Unit of NAMMDR.

Non-interventional PASS may be conducted by the MAH on a voluntary basis or imposed under certain conditions:

  • as a condition in accordance with Art. 731, 733 of Law no. 95/2006 as republished (category 1 studies as mentioned in GVP Module V);
  • as a specific obligation in the context of a conditional marketing authorisation or a marketing authorisation under exceptional circumstances, in accordance with art. 732 of Law no. 95/2006 as republished (category 2 studies as mentioned in GVP Module V);
  • required in the Risk Management Plan (RMP) to investigate a safety concern or to evaluate the effectiveness of risk minimization activities (category 3 studies as mentioned in GVP Module V).

For imposed PASS, the PRAC Committee evaluates the study protocol and the results of these studies as presented in the interim and in the final study report.

EMA publishes protocols, abstracts and final reports of PASS studies in the HMA-EMA catalogue of real-world data studies.

Reference legislation (available on NAMMDR website):

  • Law no. 95/2006 on healthcare reform, as republished, Title XVIII – The Medicinal Product;
  • GVP Module V – Risk management systems;
  • GVP Module VIII – Post-authorisation safety studies;
  • DIRECTIVE 2001/83/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 6 November 2001 on the Community code relating to medicinal products for human use;
  • DIRECTIVE 2010/84/EU OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 15 December 2010 amending, as regards pharmacovigilance, Directive 2001/83/EC on the Community code relating to medicinal products for human use;
  • Directive 2012/26/EU of the European Parliament and of the Council of 25 October 2012 amending Directive 2001/83/EC as regards pharmacovigilance;
  • Commission Implementing Regulation (EU) No 520/2012 of 19 June 2012 on the performance of pharmacovigilance activities provided for in Regulation (EC) No 726/2004 of the European Parliament and of the Council and Directive 2001/83/EC of the European Parliament and of the Council;
  • Commission Implementing Regulation (EU) 2022/20 of 7 January 2022 laying down rules for the application of Regulation (EU) No 536/2014 of the European Parliament and of the Council as regards setting up the rules and procedures for the cooperation of the Member States in safety assessment of clinical trials;
  • Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency;
  • Regulation (EU) No 1235/2010 of the European Parliament and of the Council of 15 December 2010 amending, as regards pharmacovigilance of medicinal products for human use, Regulation (EC) No 726/2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency, and Regulation (EC) No 1394/2007 on advanced therapy medicinal products;
  • Law No. 249 of 20 July 2022 on approval of Emergency Government Ordinance no. 29/2022 regarding the establishment of an institutional framework and necessary measures for implementation of Regulation (EU) No. 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, repeal of Directive 2001/20/EC and amendment of certain healthcare regulations.