Outcomes of imposed non-interventional post-authorisation safety studies

The European Medicines Agency (EMA) publishes the outcomes of final study results of imposed non-interventional post-authorisation safety studies (PASS) for medicines authorised in the European Union (EU).

The rules on submitting results for imposed non-interventional PASS fall under Art 107q of 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.

A PASS is a study carried out after a medicine has been authorised to obtain further information on a medicine's safety, or to measure the effectiveness of risk-management measures. A PASS is non-interventional if:

• the medicine is prescribed in the usual way in accordance with the terms of the marketing authorisation;
• deciding how to treat the patient is based on current practice and not a trial protocol;
• the prescription of the medicine is separate from the decision to include the patient in the study;
• patients do not undergo additional diagnostic or monitoring procedures;
• data analysis uses epidemiological methods.

An EU competent authority may impose a non-interventional PASS, either as a condition of marketing authorisation (category 1) or as a specific obligation in a conditional marketing authorisation or a marketing authorisation under exceptional circumstances (category 2). For more information, see Guideline on good pharmacovigilance practices (GVP) - Module VIII – Post-authorisation safety studies (Rev. 3).

EMA's scientific committees (PRAC and CHMP) and the CMDh carry out the assessment of PASS study protocols and final study results. For more information, see PASS: questions and answers.

The outcomes of imposed non-interventional PASS final study results assessments for active substances found only in centrally authorised medicines are published as part of each medicine's European public assessment report (EPAR).

The outcome for nationally authorised medicinal products included in 'mixed' procedures where centrally authorised products were also involved can be found on the Community register maintained by the European Commission.

Protocols and abstracts of results of imposed non-interventional PASS are publicly available in the EU PAS Register on the European Network of Centres in Pharmacoepidemiology and Pharmacovigilance (ENCePP) website.

Outcomes for active substances contained in nationally authorised products

The table below lists the outcomes of imposed non-interventional PASS final study results for active substances contained in nationally authorised medicines, by alphabetical order.

When the assessment of PASS final study results for a nationally authorised product leads to a variation of marketing authorisations, marketing authorisation holders for products containing the active substance concerned by the PASS final report should submit a variation to align their marketing authorisation with the adopted outcome.

Marketing authorisation holders for products containing the same active substance but not concerned by the PASS final report should consider whether the proposed changes to product information apply to their products.

Chlormadinone acetate (CMA), ethinylestradiol (EE) : List of nationally authorised medicinal products - EMEA/H/N/PSR/J/0042

Reference Number: EMA/111641/2024

Chlormadinone acetate (CMA), ethinylestradiol (EE) : CMDh Scientific conclusions and grounds for variation, amendments to the Product Information and timetable for the implementation - EMEA/H/N/PSR/J/0042

Valproate - Paternal exposure to valproate (Final report)

Valproate - Paternal exposure to valproate (Corrigendum to the final report))

Valproate - Paternal exposure to valproate (Addendum)

Valproate guide for male patients

Valproate guide for healthcare professionals

Valproate : List of nationally authorised medicinal products - EMEA/H/N/PSR/J/0043

Reference Number: EMA/581954/2023

Valproate : CMDh Scientific conclusions and grounds for variation, amendments to the Product Information and timetable for the implementation - EMEA/H/N/PSR/J/0043

Valproate : PRAC non-interventional imposed PASS final study report assessment report - EMEA/H/N/PSR/J/0043

Reference Number: EMA/334781/2024

Direct healthcare professional communication (DHPC) : Valproate-containing medicines - new measures regarding the potential risk of neurodevelopmental disorders in children of fathers treated with valproate in the 3 months prior to conception

Aprotinin : List of nationally authorised medicinal products - EMEA/H/N/PSR/S/0030

Aprotinin : CMDh Scientific conclusions and grounds for variation, amendments to the Product Information and timetable for the implementation - EMEA/H/N/PSR/S/0030

Valproate : List of nationally authorised medicinal products - EMEA/H/N/PSR/J/0045

Valproate : CMDh Scientific conclusions and grounds for variation, amendments to the Product Information and timetable for the implementation - EMEA/H/N/PSR/J/0045

Valproate : PRAC non-interventional imposed PASS final study report assessment report - EMEA/H/N/PSR/J/0045

Oral retinoids: List of nationally authorised medicinal products - EMEA/H/N/PSR/J/0002

Oral retinoids: CMDh scientific conclusions, amendments to product information and implementation timetable - EMEA/H/N/PSR/J/0040

Valproate : List of nationally authorised medicinal products - EMEA/H/N/PSR/J/0036

Reference Number: EMA/490085/2023

Valproate : PRAC non-interventional imposed PASS final study report assessment report - EMEA/H/N/PSR/J/0036

AdoptedReference Number: EMA/490085/2023

Valproate: Scientific conclusions and grounds for the variation to the terms of the Marketing Authorisation(s) - EMEA/H/N/PSR/J/0036

Hydroxyethyl starch : List of nationally authorised medicinal products - EMEA/H/N/PSR/J/0031

Reference Number: EMA/605749/2022

Hydroxyethyl starch : CMDh Scientific conclusions and Conditions for lifting the suspension of the marketing authorisations - EMEA/H/N/PSR/J/0031

Hydroxyethyl starch : CMDh Divergent position - EMEA/H/N/PSR/J/0031

Hydroxyethyl starch : PRAC non-interventional imposed PASS final study report assessment report - EMEA/H/N/PSR/J/0031

AdoptedReference Number: EMA/596511/2022

Teicoplanin : List of nationally authorised medicinal products - EMEA/H/N/PSR/S/0025

Reference Number: EMA/33992/2021

Teicoplanin : CMDh Scientific conclusions and grounds for variation, amendments to the Product Information and timetable for the implementation - EMEA/H/N/PSR/S/0025

Thiocolcicoside: List of nationally authorised medicinal products - EMEA/H/N/PSR/J/0023

Reference Number: EMA/230507/2020

Thiocolcicoside: CMDh Scientific conclusions, amendments to product information and implementation timetable - EMEA/H/N/PSR/J/0023

Domperidone: List of nationally authorised medicinal products - EMEA/H/N/PSR/J/0015

Reference Number: EMA/185142/2019

Domperidone: CMDh Scientific conclusions and grounds for variation, conditions and timetable for the implementation - EMEA/H/N/PSR/J/0015

Magnesium sulphate heptahydrate, sodium sulphate anhydrous, potassium sulphate: List of nationally authorised medicinal products - EMEA/H/N/PSR/S/0016

Reference Number: EMA/854912/2018

Magnesium sulphate heptahydrate, sodium sulphate anhydrous, potassium sulphate: CMDh scientific conclusions and grounds for variation, amendments to the product information and timetable for the implementation - EMEA/H/N/PSR/S/0016

Numeta: List of nationally authorised medicinal products - EMEA/H/N/PSR/S/0017

Reference Number: EMA/850681/2018

Numeta: CMDh Scientific conclusions and grounds for variation, amendments to the Product Information and timetable for the implementation - EMEA/H/N/PSR/S/0017

Thiocolchicoside: List of nationally authorised medicinal products - EMEA/H/N/PSR/J/0008

Reference Number: EMA/224020/2018

Thiocolchicoside: CMDh Scientific conclusions and grounds for variation, amendments to the Product Information and timetable for the implementation - EMEA/H/N/PSR/J/0008

Poly (o-2-hydroxyethyl) starch: List of nationally authorised medicinal products - EMEA/H/N/PSR/S/0009

Reference Number: EMA/723696/2017

Cyproterone/ethinylestradiol: CMDh scientific conclusions, amendments to product information and implementation timetable - EMEA/H/N/PSR/J/0003

Reference Number: EMA/68246/2017

Cyproterone/ethinylestradiol: PRAC non-interventional imposed PASS final study report assessment report - EMEA/H/N/PSR/J/0003

Reference Number: EMA/101714/2017

Cyproterone/ethinylestradiol: CMDh scientific conclusions, amendments to product information and implementation timetable - EMEA/H/N/PSR/J/0005

Cyproterone/ethinylestradiol: PRAC non-interventional imposed PASS final study report assessment report - EMEA/H/N/PSR/J/0005

Reference Number: EMA/101726/2017

Cyproterone/ethinylestradiol: CMDh scientific conclusions, amendments to product information and implementation timetable - EMEA/H/N/PSR/J/0006

Cyproterone/ethinylestradiol: PRAC non-interventional imposed PASS final study report assessment report - EMEA/H/N/PSR/J/0006

Reference Number: EMA/101741/2017

Cyproterone/ethinylestradiol: List of nationally authorised medicinal products - EMEA/H/N/PSR/J/0003; EMEA/H/N/PSR/J/0005; EMEA/H/N/PSR/J/0006

Reference Number: EMA/68246/2017

Trimetazidine: CMDh scientific conclusions, amendments to product information and implementation timetable - EMEA/H/N/PSR/0001 and EMEA/H/N/PSR/J/0002

Reference Number: EMA/283107/2016

Trimetazidine: List of nationally authorised medicinal products - EMEA/H/N/PSR/0001

Reference Number: EMA/283098/2016

Trimetazidine: List of nationally authorised medicinal products - EMEA/H/N/PSR/J/0002

Reference Number: EMA/637689/2016