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.
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.
Directive 2010/84/EU introduced the principle of the European evaluation procedure of PSURs for active ingredients or combinations authorized in more than one Member State (PSUR Single Assessment or PSUSA procedure) and established the creation of a single list of active ingredients and associated DLPs (EURD list).
The assessment of PSURs under the PSUSA procedure involves the active ingredients/combinations of medicines authorized via the centralized procedure (Centrally Authorised Products or CAPs), medicines authorized by national authorization procedures and those authorised through mutual recognition or decentralized procedure (Nationally Authorised Products or NAPs).
The implementation of the outcome of the PSUSA procedures is a legal obligation for marketing authorization holders (MAHs), including those medicines exempted from participating in the procedure but containing the same active ingredients or combinations of active ingredients. Therefore, when a PSUR single assessment procedure leads to a variation of the marketing authorization, MAHs of all the products containing the active ingredients/combinations subject to the procedure are required to submit a variation application to align their products to the PSUSA procedure outcome.
The timelines for submission of the concerned variation applications may vary, depending on the type of marketing authorization and decision-making process:
- for the PSUSA procedures including CAPs, the MAHs of the medicines authorized with centralized procedure involved in the procedure do not have to submit a variation application at the end of the procedure, as the outcome is directly implemented when the European Commission issues its decision updating the EPAR on the EMA portal
- the MAHs of CAPs not involved in the PSUSA procedure should submit a variation application within 60 days from the communication received from the EMA
- if the procedure involves CAPs + NAPs, the MAHs of the NAPs should submit the request for variation according to the timelines reported in the table below*, while the above applies to CAPs.
- for PSUSA procedures involving NAPs only (medicines authorised by national, mutual recognition and decentralized marketing authorization procedures), the concerned MAHs should submit the variation application as per the timelines and criteria reported in the table below*, depending on whether the position of the CMDh was adopted by consensus or by majority.
* Timelines for submission of the variation applications for the adaptation of product information of the NAPs following the conclusion of the PSUSA procedures (PSUSA NAPs only and CAPs/NAPs procedures)
|NAPs involved in the PSUSA procedure||NAPs NOT involved in the PSUSA procedure|
|PSUSA NAPs only procedures - CMDh position by consensus||As per timetable attached to the PSUSA assessment report published on the EMA website||As per timetable attached to the PSUSA assessment report published on the EMA website|
|PSUSA NAPs only procedures - CMDh position by majority||MAHs to submit variations within 10 days after publication of the Commission Decision on the EC website. EC Decision are published on this page||MAHs to submit variations within 60 days after publication of the Commission Decision on the EC website. EC Decision are published on this page|
|PSUSA CAPs/NAPs mixed procedure||MAHs to submit variations within 60 days after publication of the Commission Decision on the EC website. EC Decision are published on this page||MAHs to submit variations within 60 days after publication of the Commission Decision on the EC website. EC Decision are published on this page|
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.
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”).
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