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Italian Medicines Agency Agenzia Italiana del Farmaco

PSURs (Periodic safety update reports)

PSURs – Periodic safety update reports

The PSUR (Periodic Safety Update Report) is a periodic evaluation of the risk-benefit balance of a medicinal product and provides an analysis of its safety and efficacy profiles throughout the medicine life cycle. The submission of a PSUR for a medicinal product to the competent authorities is regulated bi Law and shall follow relevant procedures and timelines established at European level in accordance with Community rules.

Submission of the PSUR for a medicine

The PSUR shall be sumbitted for all approved medicinal products unless they are covered by the derogation given in Directive 2001/83, Article 107b.3, regardless of the marketing status of the product.

The presentation of PSURs does not exempt the MAH from the obligation to report any important new information related to the safety and efficacy of the product, as required by current legislation and good pharmacovigilance practices.

The format and content of the PSUR are described in the GVP Module VII published on the EMA website.

When to submit the PSUR

The MAH shall check the EURD list to verify the DLP and the submission date of the PSUR for the active substance of the medicinal product. In particular, MAHs of products authorised under Articles 10(1), 10a, 14 and 16a shall check the list to verify whether the PSUR is required also for these types of products and act accordingly.

PSUR management

PSUR Work Sharing project and PSUR synchronization

With the entry into force of Directive 2010/84/EU and Regulation 1235/2010/EU, the PSUR Work Sharing (WS) and PSUR Synchronization project, launched in 2002 with the aim of harmonizing the data lock points (DLP) of PSUR by active ingredient, thus allowing the National Agencies to share work and reduce administrative burdens, is about to reach its conclusion and it is planned to complete the procedures still in the finalization phase as soon as possible. At the same time, participation in this procedure has lost its voluntary character, becoming mandatory and taking on a new legal basis, as it must be understood as a "coordinated" national request pursuant to Art. 107 paragraph (2) of Directive 2010/84/EU, as amended.

Therefore, MAHs are no longer required to send new PSURs for the work-sharing procedure, but are requested to check the publication of the results of the finalized assessments on the HMA/CMDh, with an aim to implement them.

The adaptation to the provisions of the conclusions of the PSUR WS procedures according to Extended list (modification of product information and/or other changes to the terms of the MA) for the respective active ingredient/association of active ingredients is, as mentioned, mandatory.

The list of active ingredients still involved in the project and related DLPs is available on the HMA website (“List of substances under PSUR Work Sharing scheme and other substances contained in Nationally Authorised Products with DLP synchronised” o “Extended list”) and shall be available until the end of the project.

The summaries of the PSUR assessment procedures (or Summary Assessment Report), according to the PSUR Work Sharing and PSUR Synchronization project, after approval by the CMDh, are published monthly, since December 2013 on the HMA/CMDh website, so that all MAHs, including those of medicinal products that are not required to submit PSURs, update the product information of their medicinal products as required by the conclusions of the assessment procedure.

All MAHs shall submit an appropriate application to change the terms of the authorization within 90 days from the publication of the Summary Assessment Report, or within the timeframe indicated in the Summary Assessment Report if otherwise provided.

Evaluation of PSURs in the PSUSA procedure

Directive 2010/84/EU introduced the principle of the single European evaluation of PSURs (PSUSA procedure or PSUR Single Assessment) for active ingredients or combinations authorized in more than one Member State and establishes the creation of a single list of active ingredients and of associated DLPs (EURD list).

The assessment of PSURs under the PSUSA procedure involves the active ingredients/combinations of medicines authorized with centralized procedure (CAP) in medicines authorized with national, mutual recognition or decentralized procedures (NAP) and medicines authorized with CAP + NAP procedure.

The adaptation to the recommendations and conclusions of the PSUSA procedures is a legal obligation for marketing authorization holders, also including medicines exempted from participation in the procedure but containing the same active ingredients or combinations of active ingredients. Therefore, when a single PSUR assessment procedure leads to a variation of the terms of the marketing authorization, all MAHs of products containing the active ingredient subject to the procedure are required to submit a variation application to align their products as a result of the above procedure.

The timing of implementation for the adaptation to the conclusions of the PSUSA procedures may vary, depending on the type of marketing authorization:

  • for the PSUSAs of CAPs, the MAHs of the medicines authorized with centralized procedure involved do not have to submit an application for variation at the end of the procedure, because the outcomes are directly implemented when the European Commission issues its decision, through updating of the EPAR on the portal of the EMA
  • if the procedure involves CAP + NAP, the holders of the NAP medicines submit an adequate request for variation within 30 days from publication of the decision of the European Commission, while the above applies to CAPs. The decisions of the European Commission are published on this page
  • for PSUSA procedures which exclusively involve NAPs (national, mutual recognition and decentralized) and whose outcome is unanimously approved by the CMDh, the MAHs submit an application for variation within the timing indicated in the timetable attached to the assessment document which is published on the EMA website
  • for NAP procedures approved by the CMDh by majority, the MAHs submit an adequate application for variation to adopt the outcome of the assessment within 30 days from publication of the European Commission’s decision on this page

Follow up of the PSUSA: the PSUFU procedure for NAP

If at the end of a PSUSA procedure it was not possible to finalize the examination of a safety issue (for example a signal, a new risk or other safety data), the Lead MS or the PRAC may exceptionally recommend to the CMDh the implementation of a PSUFU procedure (for guidelines on Follow-Up PSURs see http://www.hma.eu/314.html), where it is deemed necessary to review such data before the date of the following PSUR.

As for the PSUSA NAP and PSUR WS procedures, a Summary Assessment Report of the procedure (SmAR) is also published for the PSUFU on the CMDh website http://www.hma.eu/611.html, which includes the Lead MS recommendations and the rationale/justification for such recommendations.

The MAHs of the medicines involved are required to periodically consult the aforementioned site to find out about the requirements to be fulfilled. In particular, if the conclusion of the PSUFU procedure has resulted in a recommendation requiring modification of the product information or, in general, of the Marketing Authorization, the texts to be implemented will also be published. The standard deadline for submitting changes is 60 days from the date of publication on the aforementioned site, unless a different date is expressly indicated in the text of the recommendation.

Documents for the PSUSA procedures and submission of PSURs

For the submission of PSURs as of 13 June 2016, the use of the PSUR Repository is mandatory. Information and instructions for registration to the repository are available on this page.

The PSUSA procedure relating to the PSUR assessment of active ingredients contained in medicinal products authorized with centralized procedure, also applied in the case of mixed PSUSA procedures of active ingredients contained in both CAP and NAP (CAP + NAP procedures), together with the EURD list and information on how to submit the PSUR, can be found on the EMA website.

The procedure relating to the assessment of PSURs of active ingredients contained in medicinal products authorized only with the national procedure can be found on the HMA/CMDh website (“CMDh Standard Operating Procedure on the Processing of PSUR Single Assessment for Nationally Authorised Products”).

PSUR of active ingredients NOT listed on the EURD list or on the Extended list

Active ingredients not listed on the EURD list (or on the Extended list) are active ingredients authorized in one Member State only. Therefore, the submission of the PSUR is subject to the normal sending frequency required by current legislation, as also specified in chapter VII.C.2. Standard submission schedule of PSURs of Module VII of the GVP - Periodic safety update report, except for different conditions imposed at the time of the marketing authorization by the competent authority.

In the event that the active ingredient/combination of active ingredients is not on the EURD list but the medicine is authorized in more than one European Member State, an email can be sent to the EMA to EURDList@ema.europa.eu

Since the use of the PSUR Repository for the filing of PSURs has become mandatory as of 13 June 2016, MAHs of medicinal products containing active ingredients/combinations of active substances authorized only in a member state are required to send their PSURs through the PSUR Repository, according to the methods described above

Nested Applications

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