Safety updates

Updated 11 December 2015

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 PSURs be submitted until the PSUR repository takes effect?

Until the PSUR repository takes effect on 13 June 2016, the submission of PSURs varies depending on how the products were authorised. After 13 June 2016, PSURs should only be sent to the PSUR repository.

CAP PSURs should be submitted to:

  • EMA: PSURs are submitted in eCTD format via eSubmission Gateway/Web Client
  • PRAC rapporteur
  • Other PRAC members

NAP PSURs, which form part of a single assessment procedure, should be submitted to various recipients depending on whether the PSUR forms part of a single assessment procedure with NAP PSURs only, or whether the procedure also includes CAP PSURs, see table below:

 

Only NAP in the procedure

Both CAP and NAP in the procedure

PSURs should be submitted to

All NCAs* with a marketing authorisation

Lead Member State for the procedure (if this is not included above)

EMA (submitted in eCTD or Nees format via eSubmission Gateway/Web Client)

All NCAs* with a marketing authorisation

PRAC rapporteur for the procedure (if this is not included above)

EMA (submitted in eCTD or Nees format via eSubmission Gateway/Web Client)

*NCA: National Competent Authority

For products not yet in the EURD list, PSURs should be submitted to the NCAs that issued the marketing authorisation for the products.

For more information about the requirements for the submission of PSURs, see HMA's website and EMA's website

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. 822 of 1 August 2012 on monitoring of adverse reactions from medicinal products (Danish title: Bekendtgørelse nr. 822 af 1. august 2012 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