Safety updates

Updated 07 February 2019

Periodic safety update reports (PSUR)

The PSUR provides an overview of both the benefits and risks of a medicinal product. Consequently, the periodic safety update report is also referred to as a Periodic Benefit Risk Evaluation Report (PBRER).

A periodic safety update report must include:

  • a list of the adverse reactions known to the company
  • an estimate of the number of humans or animals exposed to the medicinal product
  • an overall safety evaluation of the medicinal product
  • proposals for new safety measures, if relevant
  • an overall evaluation of the benefits of the medicinal product
  • a scientific evaluation of the benefit-risk ratio of the medicinal product based on information from primarily clinical trials, scientific literature and adverse reaction reports.

When should a PSUR be submitted?

The European Medicines Agency (EMA) has published a reference dates list and submission frequencies of periodic safety update reports (PSUR). This list is referred to as the EURD list. The EURD list is a list of active substances and combinations of active substances contained in medicinal products authorised under various procedures (national procedure, MRP/DCP, centralised procedure) in the EU. The list states the EU reference date, the PSUR submission frequency and the next data lock point (DLP) for each substance or combination of substances.

The information contained in the EURD list for a certain substance or combination of substances takes effect 6 months after the publication date on the list.

Marketing authorisation holders (MAH) are obliged to submit PSURs according to the dates published in the EURD list.

MAHs must submit PSURs in accordance with the below information:

  • If the substance/combination of substances is in the EURD list, the PSUR frequency and DLP in this list should be followed. The EURD list overrules the PSUR frequency and DLP (see the last bullet below) as described in Article 107c (2) of Directive 2010/84/EU as well as any other condition described in the marketing authorisation.
  • If the substance/combination of substances is not in the EURD list, you should check whether it has been added to the “List of substances under PSUR Work Sharing scheme and other substances contained in Nationally Authorised Products with DLP synchronised”. If this is the case, you should follow the frequency and DLP stated in this list.
  • If the substance/combination of substances is not in these two lists, follow the PSUR frequency described in Article 107c (2) of Directive 2010/84/EU:
    1. every six months after the marketing authorisation was issued in Denmark and until the product has been placed on the market
    2. every six months in the first two years after the product was placed on the market
    3. annually for the subsequent two years
    4. then at three-yearly intervals.

How should a PSUR be submitted?

As of 13 June 2016, the use of the PSUR Repository is mandatory.

The PSUR Repository is a central platform for the storage and exchange of PSURs and related documents between regulatory authorities and pharmaceutical companies in the EU. The platform is based on the pharmacovigilance legislation to facilitate the exchange of information between regulatory authorities and pharmaceutical companies. The PSUR Repository should only be used for medicinal products for human use. Read more about the PSUR Repository

Marketing authorisation holders (MAH) must use the PSUR Repository as the only submission method and there should be no PSUR submissions directly to the national competent authorities onwards. The use of the PSUR Repository is now mandatory for centrally, nationally, MRP and DCP authorised products, and it supports both the EU Single Assessment Procedure as well as the PSUR national procedure.

PSURs not submitted directly to the PSUR Repository will be excluded from the PSUR assessment procedure. If PSURs are not submitted to the PSUR Repository, the MAH has not fulfilled the legal obligation applying to the submission of PSURs.

All PSURs should be submitted to the PSUR Repository via the eSubmission Gateway/Web Client The MAH needs to register as a user on the eSubmission registration page PSURs must be submitted in eCTD or Nees format. All other formats will be rejected.

Before making submissions to the PSUR Repository, the MAH must make sure that the information on authorised products is correct in the Article 57 database. The reason is that the information in the Article 57 database is linked to the PSUR Repository. If the information about a product is not correct in the Article 57 database, the PSUR cannot be uploaded. Correct updating of the Article 57 database is mandatory according to the pharmacovigilance legislation. Read more about the submission of information on medicinal products to the Article 57 database

More information on the PSUR Repository as well as guidelines and tutorials about user registration, how to submit PSURs and in which format

You can contact the EMA if you have any questions regarding the PSUR Repository and the eSubmission Gateway/Web Client via the EMA Service Desk portal.

Announcement of the outcome of PSUR assessments

Marketing authorisation holders are obliged to keep updated about their substance(s) and to make sure that their SPCs are updated. This also applies in cases where submission of routine PSURs is not required (in case of e.g. generics). This includes updates in accordance with the outcome of PSUR assessments.

Single assessment procedures

The authorisation type forming part of the PSUSA procedure determines where the outcome of the single assessment procedure is available, see the table below.

Included in the PSUSA procedure

Only CAP products

Both CAP and NAP products

Only NAP products

PSUSA results are available at:

See EMA's website under the EPAR of the individual product

See Community register

See EMA's website

Work Sharing (WS) procedures

Single assessment is now used for both CAP and NAP products; consequently new work sharing procedures are not created. However, ongoing work sharing procedures need to be completed.

The outcome of PSUR assessments under the work sharing procedure is announced on the website of CMDh’s (Co-ordination Group for Mutual recognition and Decentralised Procedures – human)

PSURs for generic medicinal products and other medicinal products for which PSURs are not routinely required

Routine periodic safety update reports are not required for the following medicinal products:

  • generic medicinal products
  • medicinal products containing an active substance, for which well-established medicinal use has been demonstrated
  • homeopathic medicinal products or
  • traditional-use herbal medicinal products

PSURs should only be submitted for the above-mentioned medicinal products if it appears specifically from the EURD list or the "List of substances under PSUR Work Sharing scheme and other substances contained in Nationally Authorised Products with DLP synchronized". If the substance for the generic medicinal product is not in one of these two lists, PSURs should only be submitted if it has been determined in the marketing authorisation in connection with the authorisation of the medicinal product or if the Danish Medicines Agency has requested a PSUR.

Marketing authorisation holders of the above-mentioned medicinal products are obliged to keep updated about the outcome of WS and single assessment PSURs. Marketing authorisation holders of generic medicinal products, for which submission of routine PSURs is not required, must always inform the national competent authorities and the Lead Member State/PRAC rapporteur if they become aware of a new safety-related issue.

What happens to the periodic safety update reports?

The Danish Medicines Agency reviews the periodic safety update reports, often in cooperation with the other EU member states. As part of the review, we take into account:

  • has the PSUR been prepared as described in the GVP guideline – module VII?
  • is the scientific quality acceptable, and are relevant results from clinical trials, scientific literature as well as adverse reaction reports discussed in the PSUR?
  • do we agree with the scientific conclusions and any proposals for improving the safety of the product? 
  • is the safety profile of the product reflected in the summary of product characteristics?
  • has the MAH provided sufficient information to assess the safety or do we need more information?

The outcome of the review may be that the summary of product characteristics and the package leaflet need to be changed.

More information

Executive Order no. 1191 of 6 November 2017 on monitoring of adverse reactions from medicinal products (Danish title: Bekendtgørelse nr. 1191 af 6. november 2017 om bivirkningsovervågning af lægemidler)

Commission Implementing Regulation (EU) No 520/2012 of 19 June 2012 on the performance of pharmacovigilance activities

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, as amended by Regulation 1235/2010 regarding pharmacovigilance of medicinal products for human use

GVP guideline – module VII

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