Post Authorisation Safety Study
A Post Authorisation Safety Study (PASS) is:
- a safety study of an authorised medicine aiming to identify, characterise, quantify a safety hazard, confirm the safety profile of a medicine or measure the effectiveness of risk-management measures.
- a safety study where the medicine is used in compliance with the terms of the marketing authorisation.
PASSs can either be clinical trials (intervention studies) or non-interventional studies.
PASSs may be initiated by the marketing authorisation holder voluntary or may be imposed by a specific obligation of the medicine’s marketing authorisation. PASSs may be carried out in one or several EU/EEA Member States.
Further information about PASSs is available in this European Guideline on good pharmacovigilance practices (GVP).
1. When must PASSs be authorised by the Danish Medicines Agency?
A clinical trial of medicinal products in humans may be carried out in Denmark only after authorisation by the Danish Medicines Agency, see section 88(1) of the Danish Medicines Act. This applies also to PASSs which are clinical trials. Furthermore, trials in humans must be approved by a research ethics committee, see the Danish Act on the Review of Health Research Projects and Health Data Research Projects. Read more about clinical trials.
A non-interventional study which is an obligation of a marketing authorisation and which has been established after the issue of the marketing authorisation, see section 9(2) of the Danish Medicines Act, may commence only after authorisation by the Danish Medicines Agency if the study is only to be carried out in Denmark, see section 92b(1) of the Danish Medicines Act.
2. When must non-interventional studies be authorised by PRAC?
A non-interventional study which is an obligation of a marketing authorisation, see section 9 of the Danish Medicines Act, and which is to be carried out in more than one EU/EEA Member States, or where the Danish Medicines Agency has laid down terms for the study in connection with the issue of the marketing authorisation, see section 9(1) of the Danish Medicines Act, may commence only when the Pharmacovigilance Risk Assessment Committee (PRAC) under the European Medicines Agency (EMA) has authorised the study, see section 92b(2) of the Danish Medicines Act. The study is not subject to authorisation by the Danish Medicines Agency. Read more about PRAC and application for authorisation of non-interventional studies.
A non-interventional study which is an obligation of a marketing authorisation which is authorised by a Community Marketing Authorisation issued by the European Commission may commence only when PRAC has authorised the study, see article 28b(1) of Regulation 726/2004 (as amended by Regulation 1235/2010) and article 107n(3) of Directive 2001/83/EC (as amended by Directive 2010/84/EU).
Voluntary non-interventional studies
Non-interventional studies initiated voluntarily by the marketing authorisation holder are not subject to authorisation by the Danish Medicines Agency.
Further information about PASSs is available in this European guideline: Guideline on good pharmacovigilance practices (GVP).
3. Applying to the Danish Medicines Agency
An application for authorisation to commence a non-interventional study must be submitted to the Danish Medicines Agency via Eudralink by email to LMU@dkma.dk.
An application is required when the Danish Medicines Agency has laid down terms on the study after the issue of a marketing authorisation, and if the study is only to be carried out in Denmark.
4. What must be included in the application to the Danish Medicines Agency?
The application must include a draft study protocol containing a detailed description of the study purpose and study design, see section 2(2) of Danish Executive Order No 897 of 23 June 2016 on Non-Interventional Studies.
The study protocol must be presented in the format laid down in Annex III of implementing regulation (EU) no 520/2012 of 19 June 2012 on the performance of pharmacovigilance activities, see article 38 of the regulation.
Please send the application with a cover letter detailing the following:
- Date of registration in the EU PAS Register and registration number
- An indication that the study is imposed with reference to the obligation of the marketing authorisation
- The place where the study is to take place in Denmark
5. When will the Danish Medicines Agency make its decision?
The Danish Medicines Agency will decide on the application no later than 60 days after having received the application and draft study protocol, see section 3(1) of the Danish Executive Order on Non-Interventional Studies.
6. When may the Danish Medicines Agency object to and reject an application?
The Danish Medicines Agency may raise its justified objections and may if necessary reject the application if it is assessed that the conduct of the study will promote the use of the medicinal product or the study is designed in such a way that the study purpose cannot be achieved, see section 3(2) of the Danish Executive Order on Non-Interventional Studies.
7. Is an application required for authorisation of protocol amendments?
- Before the marketing authorisation holder makes substantial amendments to the study protocol of a non-interventional study authorised by the Danish Medicines Agency, the marketing authorisation holder must apply for authorisation thereof, see section 6(1) of the Danish Executive Order on Non-Interventional Studies.
- An application to amend the study protocol must be submitted to the Danish Medicines Agency, which will decide if the amendment applied for may be authorised, see section 6(2) of the Danish Executive Order on Non-Interventional Studies.
- The application must include a draft amended study protocol and a justification for the amendments, see section 6(2) of the Danish Executive Order on Non-Interventional Studies.
- The application must be submitted to the Danish Medicines Agency via Eudralink by email to LMU@dkma.dk.
Before the marketing authorisation holder makes substantial amendments to the study protocol of a non-interventional study authorised by PRAC, the marketing authorisation holder must apply for authorisation thereof. An application to amend the study protocol must be submitted to PRAC, which will decide if the amendment applied for can be authorised. The application must include a draft amended study protocol and a justification for the amendments, see section 7 of the Danish Executive Order on Non-Interventional Studies and article 28b(1) of Regulation 726/2004 (as amended by Regulation 1235/2010) and article 107o of Directive 2001/83/EC (as amended by Directive 2010/84/EU). Further information is available on the website of the European Medicines Agency.
8. Is submission of a report on the results of the study required?
The marketing authorisation holder must submit a report on the results of a non-interventional study conducted in Denmark to the Danish Medicines Agency, see section 92c(1) of the Danish Medicines Act, except if the study has been authorised by PRAC. In this case, the marketing authorisation holder must submit a report on the results of the non-interventional study to PRAC, see section 92c(2) of the Danish Medicines Act and article 28b(1) of Regulation 726/2004 (as amended by Regulation 1235/2010) and article 107p of Directive 2001/83/EC (as amended by Directive 2010/84/EU).
Submission to the Danish Medicines Agency must take place within 12 months of the end of data collection unless a waiver has been granted by the Danish Medicines Agency, see section 92c(1) of the Danish Medicines Act. The report must be submitted to the Danish Medicines Agency via Eudralink by email to LMU@dkma.dk.
Submission to PRAC must take place within 12 months of the end of data collection unless a waiver has been granted by PRAC, see section 92c(2) of the Danish Medicines Act and article 28b(1) of Regulation 726/2004 (as amended by Regulation 1235/2010) and article 107p of Directive 2001/83/EC (as amended by Directive 2010/84/EU).
9. In what other situations must the Danish Medicines Agency be notified of a non-interventional study?
The marketing authorisation holder must also submit a report on the results of a voluntary non-interventional study conducted in Denmark, see section 92c(1) of the Danish Medicines Act. Submission must take place within 12 months of the end of data collection unless a waiver has been granted by the Danish Medicines Agency, see section 92c(1), 2nd sentence, of the Danish Medicines Act.
If PRAC has authorised the protocol of a non-interventional study, the marketing authorisation holder must forward the protocol to the competent authorities of the Member States in which the study is to be conducted and may thereafter commence the study according to the endorsed protocol, see article 28b(1) of Regulation 726/2004 (as amended by Regulation 1235/2010) and article 107n(3) of Directive 2001/83/EC (as amended by Directive 2010/84/EU). The Danish Medicines Agency should be notified if Denmark is among the countries where the study is going to be conducted.
If PRAC has authorised substantial amendments of an authorised protocol, the marketing authorisation must notify the Member States in which the study is to be conducted, see article 28b(1) of Regulation 726/2004 (as amended by Regulation 1235/2010) and article 107o of Directive 2001/83/EC (as amended by Directive 2010/84/EU). The Danish Medicines Agency should be notified if Denmark is among the countries where the study is going to be conducted.
Read more in Annex to GVP module VIII - Post-authorisation safety studies.
Please send the notification with a cover letter detailing the following:
- Date of registration in the EU PAS Register and registration number
- An indication whether the study is voluntary or imposed (an obligation of the marketing authorisation)
- The study is or was conducted in Denmark
- The date when authorised by PRAC if relevant
The notification must be submitted to the Danish Medicines Agency via Eudralink by email to lmu@dkma.dk.
Further details on the information to be submitted to the Danish Medicines Agency in relation to PASSs are available in the Guideline on good pharmacovigilance practices (GVP).
10. When and how should draft articles about PASSs be submitted?
It appears from GVP VIII.B.5.1 that the marketing authorisation holder should submit a draft article (manuscript) on the results of a PASS to the EMA and the competent authorities of the EU/EEA Member States no later than two weeks after first acceptance for publication.
Draft articles can be submitted to the Danish Medicines Agency via Eudralink by email to LMU@dkma.dk.
Further information is available in the Guideline on good pharmacovigilance practices (GVP).