This page lists questions that marketing-authorisation holders (MAHs) may have on periodic safety update reports (PSURs). It provides an overview of the European Medicines Agency's position on issues that are typically addressed in discussions or meetings with MAHs in the post-authorisation phase. Revised topics are marked 'New' or 'Rev.' upon publication.
A PDF version of the entire post-authorisation guidance is available:
- European Medicines Agency post-authorisation procedural advice for users of the centralised procedure
These questions and answers have been produced for guidance only and should be read in conjunction with the rules governing medicinal products in the European Union, volume 2, notice to applicants.
MAHs must in all cases comply with the requirements of Community legislation. Provisions that extend to Iceland, Liechtenstein and Norway by virtue of the European Economic Area agreement are outlined in the relevant sections of the text.
- 1. What is a Periodic Safety Update Report (PSUR)? Rev. September 2014
Periodic safety update reports are pharmacovigilance documents intended to provide a safety update resulting in an evaluation of the impact of the reports on the risk-benefit balance of a medicinal product. They shall be submitted by marketing authorisation holders at defined time points during the post-authorisation phase.
The legal requirements for submission of PSURs are established in the Regulation (EC) No 726/2004 and the Directive 2001/83/EC.
The format of PSURs shall follow the structure described in the Commission implementing Regulation (EU) No 520/2012.
Further details and guidance for the submission of PSURs in the EU, including the list of Union references dates and frequency of submission are provided in Module VII “Periodic safety update report” of the Guideline on good pharmacovigilance practices (GVP) and in the following questions and answers.
- Regulation (EC) 726/2004
- Directive 2001/83/EC
- Commission implementing Regulation (EU) No 520/2012 of 19 June 2012 on the performance of pharmacovigilance activities provided for in Regulation (EC) No 726/2004 of the European Parliament and of the Council and Directive 2001/83/EC of the European Parliament and of the Council
- European Commission questions and answers on transitional arrangements concerning the entering into force of the new pharmacovigilance rules provided by Directive 2010/84/EU amending Directive 2001/83/EC and Regulation (EU) No 1235/2010 amending Regulation (EC) No 726/2004 (SANCO/D5/FS/(2012)1014848)
- Heads of Medicines Agencies-European Medicines Agency questions and answers on practical transitional measures for the implementation of the pharmacovigilance legislation
- Guideline on good pharmacovigilance practices (GVP) – Module VII – PSURs
- International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guideline E2C (R2) Periodic benefit-risk evaluation report (PBRER), step 5
- Guideline on GVP: Annex I - Definitions
- 2. What is the scope of PSUR assessment under the EU single assessment? Rev. September 2014
The Pharmacovigilance Risk Assessment Committee (PRAC) is in charge of issuing recommendation on the PSUR assessment for a single centrally authorised product and of the EU PSUR single assessment.
The EU PSUR single assessment, referred also as PSUSA, is the assessment of PSURs for medicinal products subject to different marketing authorisations containing the same active substance or the same combination of active substances and for which the frequency and dates of submission of PSURs have been harmonised in the list of EU reference dates (referred also as EURD list). These PSURs will be jointly assessed by the PRAC or a Member State appointed by the CMDh and results in one single assessment report, which will be shared amongst all the Marketing Authorisation Holders (MAHs) whose medicinal product(s) are part of the PSUR single assessment procedure.
Overall, the PRAC will issue a recommendation for the assessment of the following PSURs:
- PSURs of centrally authorised product(s);
- PSURs of any mix of centrally authorised products and nationally authorised products (including through the mutual recognition and decentralised procedures);
- PSURs of nationally authorised products.
Please note that, for nationally authorised medicinal products which are marketed in only one Member State and whose active substance or combination of active substances is included in the EURD list, the MAH should submit a PSUR as part of PSUSA procedure. Note that a PSUSA is foreseen for each active substance or combination of active substances registered in the EURD list.
The PSUSA involving only nationally authorised medicinal products will start at the end of 2014 i.e. products with data lock points (DLPs) falling on or after the 01/09/2014. Until the single assessment procedure involving only nationally authorised medicinal products starts MAHs should follow where applicable the “List of substances under PSUR Work Sharing scheme and other substances contained in Nationally Authorised Products with DLP synchronised”. For more information about this list please refer to the CMDh webpage for the PSUR Work sharing and Synchronisation Project. For purely nationally authorised medicinal products, containing substances or combination of actives substances not included in the EURD list, for which no PSUSA procedure has been established, the assessment of the PSURs will remain at national level.
Purely nationally authorised medicinal products are considered those which contain substances or a combination of actives substances which are only authorised in one Member State.
- 3. How shall I present my PSUR and in which format? Rev. December 2014
The format and content of the PSUR, is legally required according to Commission implementing Regulation (EU) No 520/2012 since January 2013 and is further described in the Guideline on good pharmacovigilance practices (GVP) Module VII – Periodic safety update report.
In addition, the required format and content of PSURs in the EU are based on those for the Periodic Benefit Risk Evaluation Report (PBRER) described in the ICH-E2C(R2) guideline (see Annex IV ICH-E2C(R2). To keep the terminology consistent with the one used in the EU legislation, the new PBRER continues to be described as PSUR.
Unless otherwise requested by competent authorities, the marketing authorisation holder shall prepare a single PSUR for all its medicinal products containing the same active substance with information covering all the authorised indications, route of administration, dosage forms and dosing regiments, irrespective of whether authorised under different names and through separate procedures. Even if a single PSUR is prepared for several products, please note that for medicinal products with documentation previously submitted in eCTD format, PSURs should be presented in a new eCTD sequence in the respective eCTD lifecycle of the concerned product. Where relevant, data relating to a particular indication, dosage form, and route of administration or dosing regimen, shall be presented in a separate section of the PSUR and any safety concerns shall be addressed accordingly.
Within the PSUR, the marketing authorisation holder is required to consider the impact of the data and evaluations presented within the report, on the marketing authorisation. Based on the evaluation of the cumulative safety data and the risk-benefit analysis, the marketing authorisation holder shall draw conclusions in the PSUR as to the need for changes to the product information of the products covered by the PSUR. For the purpose of analysing the impact of the PSUR data, the MAH can establish a so-called reference product information which should include “core safety” and “authorised indications” components, as explained in the GVP module VII on PSURs (section VII.B.4. ‘Reference information’). The changes proposed to the labelling can be based on the reference product information. However as the reference product information might be different for the various EU product information, it is therefore essential that the MAH considers the proposed changes for the reference product information in the context of the different EU product information for the products covered by the submitted PSUR and this should be clearly discussed in both the conclusions and actions section of the body of the PSUR as well as in the EU regional appendix.
In the EU regional appendix, sub-section “Proposed product information” of the PSUR, the marketing authorisation holder should provide their proposal for product information (SmPC and package leaflet) changes based on the above mentioned evaluation. These should take into account all EU authorised indications for products containing that active substance or combination of active substances. For marketing authorisation holders of nationally authorised products with a large number of marketing authorisations with different product information, the Agency will also accept that the core message of the proposed changes to the product information be included in the EU regional appendix as described below (see also question below “How can I propose changes to the Product Information within the PSUR for NAPs which are part of an EU single assessment?”).
The submission of the PSURs should be as follows:
- PSURs for centrally authorised products must be submitted in eCTD format only via the eSubmission Gateway or eSubmission Web Client.
- PSURs for nationally authorised products that are subject to a PSUSA procedure should be submitted via the eSubmission Gateway or eSubmission Web Client in eCTD although Non eCTD electronic Submission (NeeS) format is also accepted. It is essential to follow the published ‘file naming conventions’ in section 5 of the Introductory cover note to the List of European Union reference dates and frequency of submission of Periodic Safety Update Reports. Failing to do so might result in ‘non-acknowledgement’ of your submission.
The submission should include a cover letter containing the following formatted table template to facilitate the registration of the submission. This table should be completed in accordance with the published EURD list, where the procedure number is the combination of a unique ID and the applicable Data Lock Point (DLP) in YYYYMM format. For any medicinal product which is nationally authorised (i.e. through MRP, DCP or National procedures) it is important to highlight in Annex I of the cover letter the legal basis under which the product was authorised, in particular for those medicinal products authorised under Articles 10(1), 10a, 14 and 16a of Directive 2001/83/EC.
All the entries in the EURD list have been assigned a procedure number presented in the column “Procedure number of the PSUR single assessment”. This procedure number was initially only applicable to PSUSA procedures containing CAPs and NAPs. The number should be applied now to all procedures starting from October 2014 onwards which contain single CAPs, a mixture of CAPs, a mixture of NAPs or a mixture of CAPs and NAPs.
In order to facilitate the identification of procedures containing centrally and/or nationally authorised substances, the extra columns “Centrally Authorised Product (CAP) and “Nationally authorised product (NAP)” have been added in the EURD list”.
In line with article 57(2) of Regulation (EU) No 1235/2010 all holders of marketing authorisations for medicines in the European Union and the European Economic Area must submit information to the European Medicines Agency on authorised medicines and keep this information up-to-date. This is a legally binding requirement from the EU pharmaceutical legislation. The Agency uses this information to support the analysis of data, regulatory activities and communication. In relation to the submission of PSURs, this will facilitate the processing of the submissions in the upcoming PSUR Repository.
Please see question "To whom should I submit my PSUR?” for further details on submission requirements.
- 4. How can I submit the proposed changes to the Product Information within the PSUR for NAPs which are part of an EU single assessment? NEW December 2014
According to the guidance set out in the GVP module VII on PSURs, proposed changes to the EU labels as a result of the PSUR data should be provided under Section VII.C.5.1. PSUR EU regional appendix, sub-section “Proposed product information” of the PSUR.
It should be presented as a tracked change version of each EU SmPCs and package leaflets of the products concerned and each product information should be translated into English language including the tracked changes proposed, in order to enable the EU single assessment.
However, this can result in having to submit a large number of sets of tracked change Product Information with the additional burden of providing translations. Hence MAHs can consider the option to focus on the proposed amendments to SmPC and Package Leaflet. In such case, only the amended parts of the SmPC and Package Leaflet should be provided in track changes and in English language under the EU regional appendix.
In case no changes to the Product Information are being proposed as part of the PSUR, the MAH should not include any product information within the EU regional appendix.
- 5. What is the List of European Union reference dates (EURD list) and frequency of submission of PSURs? Rev. September 2014
The list of Union reference dates and frequency of submission of PSURs” (so-called the “EURD list”) consists of active substances and combinations of active substances, for which PSURs shall be submitted in accordance with the EU reference dates and frequencies determined by the Committee for Medicinal Products for Human Use (CHMP) and the Coordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh) following consultation with the Pharmacovigilance and Risk Assessment Committee (PRAC).
The European Union reference date (EURD) corresponds to the date of the first or the earliest known date of the marketing authorisation in the EU of a medicinal product containing the active substance or combination of active substances.
In addition to the EU reference dates and frequencies of PSURs, the EURD list also provides the Data Lock Point (DLP) of the next PSUR submissions.
The EURD list facilitates the harmonisation of DLPs and frequency of submission of PSURs for medicinal products containing the same active substance or the same combination of active substances subject to different marketing authorisations, authorised in more than one Member State. This will, where appropriate, allow one single assessment of PSURs for products containing the same active substance.
The PSUR frequency as published on the EURD list for a given active substance or combination of active substances overrules the standard submission cycle (i.e. 6-monthly, yearly and thereafter 3-yearly) set out in the legislation and any condition related to the frequency of submission of PSURs included in the Marketing Authorisation. However, National Competent Authorities (NCAs) may still request the submission of a PSUR at any given time.
The EURD list is a living document, meaning that it can be amended whenever considered necessary by the PRAC, CHMP or CMDh in response to the emergence of relevant new safety information, newly authorised substances or requests from the marketing authorisation holders.
Full information on the EURD list is included in the GVP Module VII – Periodic safety update report and the introductory cover note to the EURD list.
For guidance on submission of requests for amendment of the EURD list, please refer to the question “How can I request to amend the list of EU reference dates”.
- 6. When does the EURD list become legally binding? Rev. September 2014
The EURD list is updated on a monthly basis and changes in the PSUR submission frequencies and dates of submission come into force 6 months after its publication. This publication occurs after adoption of the EURD list by the CHMP and CMDh following consultation of the PRAC.
Since changes become binding 6 months after publication, there might be situations where “ad hoc” PSUR submissions would be necessary prior to the new frequency taking effect.
A note on this “ad hoc” PSUR will also be included in the EURD list.
- 7. How can I request to amend the list of EU reference dates? Rev. March 2013
Marketing authorisation holders can submit requests to the CHMP or the CMDh, as appropriate, to determine the Union reference dates or to change the frequency of submission of PSURs on one of the following grounds:
- for reasons relating to public health;
- in order to avoid a duplication of the assessment;
- in order to achieve international harmonisation.
The request and its grounds should be considered by the PRAC and the CHMP if it concerns at least one marketing authorisation granted in accordance with the centralised procedure or the CMDh otherwise, which will either approve or deny the request.
The list will then be amended accordingly when appropriate and published on the European medicines website.
For more details on how to submit amendments to the list, please refer to the EURD list cover note (sections 2 and 5).
- 8. Do I have to submit a PSUR if the active substance/combination of active substances of my medicinal product is not on the EURD list? Rev. September 2014
If the active substance contained in the medicinal product is not included in the EURD list, the MAH should continue to submit PSUR to the National Competent Authority (NCA) where the product is authorised, in accordance with the conditions specified in the marketing authorisation (MA), or otherwise according to the standard submission schedule of PSURs (i.e. 6 month intervals, yearly and thereafter 3 yearly). Marketing authorisation holders for certain medicinal products, such as medicinal products authorised under Article 10(1) or 10a of Directive 2001/83/EC, a homeopathic simplified registration or a traditional-use registration are not required to submit PSURs, unless there are specific requirements in the MA for the product. PSURs shall also be submitted upon request of National Competent Authorities.
For more details on PSUR submissions for generics, products containing well-established substances, homeopathic or herbal medicinal products, please refer to the question Do I have to submit a PSUR my medicinal product if it is a generic, a product containing a well-established substance, a homeopathic or herbal medicinal product?
- 9. Do I have to submit a PSUR if the combination of active substances of my product is not on the EURD list but one or more individual components are listed? Rev. March 2013
If the specific fixed dose combination is not listed in the EURD list, PSURs should not be submitted according to the EURD list entry of one or more individual components. However PSURs should be submitted as specified in the conditions of the marketing authorisation for the combination product (if any), or otherwise according to the standard submission cycle (i.e. 6-monthly, yearly and thereafter 3-yearly) unless the combination medicinal product falls within the categories of medicinal products exempted from the obligation to submit PSURs.
MAHs or National Competent Authorities can request the inclusion of the fixed combination in the EURD list for reasons related to public health, in order to avoid duplication of assessment or in order to achieve international harmonisation. Instructions on how to submit requests to amend the EURD list can be found on the EURD list webpage.
- 10. Do I have to submit a PSUR for my medicinal product if it is a generic, a product containing a well-established substance, a homeopathic or herbal medicinal product? Rev. September 2014
Medicinal products authorised under Articles 10(1), 10a, 14 or 16a of Directive 2001/83/EC are exempted from routine submission of PSURs unless otherwise specified in the marketing authorisation or required through the EURD list (see dedicated column “Are PSURs required for products referred to in Articles 10(1), 10a, 14, 16a of Directive 2001/83/EC as amended? Yes/No”). National Competent Authorities can also request PSUR for generic medicinal products at any time on the grounds detailed in Article 107c (2) of the Directive.
For medicinal product containing a known active substance, the requirement to submit a PSUR is only waived for those authorised under the legal basis mentioned above. Medicinal products containing a known substance authorised through another legal basis are required to submit PSURs.
Medicinal products which have been authorised through the equivalent legal basis as the current Articles 10(1) and 10a legal basis before the re-codification of the Directive 2001/83/EC i.e. respectively Article 4.8 a(iii), first paragraph (essential similarity) of Directive 65/65/EEC / 10 a(iii), first paragraph of Directive 2001/83/EC and Art 4.8 a(ii) (well established use) of Directive 65/65/EEC / 10.1 a(ii) of Directive 2001/83/EC are, by analogy, not required to submit PSUR unless there is a specific condition in the authorisation or there is an indication in the EURD list that PSUR submission is required, or in response to a specific request.
- 11. As a MAH of products referred to in Articles 10(1), 10a, 14 and 16a of Directive 2001/83/EC, how should I communicate any safety information to National Competent Authorities and the Agency? Rev. September 2014
Medicinal products authorised under Articles 10(1), 10a, 14 or 16a of Directive 2001/83/EC are exempted from routine submission of PSURs. Therefore, alternative mechanisms such as signal management and emerging safety issues channels should be used to communicate relevant new safety information to regulatory authorities(see GVP Module VI and Module IX).
Additionally,product information should be kept up-to-date by the MAH by submitting the appropriate variations taking account of the latest scientific knowledge or conclusions of assessments and recommendations made public by means of the EMA and National Competent Authority websites.
- 12. Do I have to submit a PSUR for my hybrid medicinal product? Rev. September 2014
Medicinal products authorised under Article 10(3) of Directive 2001/83/EC (hybrid application) are not exempted from the obligation to submit PSURs.
- 13. If the medicinal product is not marketed, is the MAH required to submit a PSUR? Rev. March 2013
MAHs are required to submit PSURs once a medicinal product is authorised in the EU, regardless of its marketing status.
- 14. Do PSURs need to contain case narratives and line listings? Rev. September 2014
The PSUR should focus on summary information, scientific assessment and integrated benefit-risk evaluation.
Marketing authorisation holders are not required to systematically include listings of individual cases, including case narratives, in the PSUR. However, they shall provide case narratives in the relevant risk evaluation section of the PSUR where integral to the scientific analysis of a signal or safety concern in the relevant risk evaluation section.
In this context “case narrative” refers to clinical evaluations of individual cases rather than the CIOMS narratives included in the individual case safety report (ICSR).
During the assessment of the PSUR, line listings for adverse reactions of special interest may be requested by the PRAC.
- 15. Can I submit a RMP update together with my PSUR? Rev. September 2014
A Risk Management Plan (RMP) update can be submitted with a PSUR for single centrally authorised medicinal product (CAP) or a mixture of CAPs belonging to the same Global Marketing Authorisation (GMA) when the changes to the RMP are a direct result of data presented in the PSUR. In this case no stand-alone RMP variation is necessary.
If the above does not apply, the updated RMP should be submitted as a stand-alone variation.
As an interim measure, submission of RMP updates cannot be accepted with PSURs subject to a PSUSA of:
- a mixture of CAPs pertaining to different GMAs;
- a mixture of centrally and nationally authorised medicinal products;
- a mixture of NAPs.
In these cases, MAHs should submit the updated RMPs as part of another procedure affecting the RMP, if one such procedure is foreseen. Alternatively, MAHs should submit a separate variation to update their RMP.
If an RMP is incorrectly submitted with a PSUR, this will be identified at the start of the procedure and both the MAH and PRAC Rapporteur will be made aware that the RMP will not be assessed and should be submitted through another appropriate procedure. If the RMP was submitted as an eCTD the MAH will have to delete that version of the RMP in the next sequence to maintain the correct lifecycle of the product.
The assessment of a PSUR may result in a recommendation to update the content of the RMP through a subsequent variation.
For nationally authorised medicinal products (i.e. authorised through MRP, DCP or National procedures), any RMP update should be submitted via a variation procedure to the National Competent Authority for assessment, even if PSURs are part of a PSUSA.
- 16. What are the timelines for the submission of PSURs? Rev. September 2014
Marketing authorisation holders should submit to the Agency PSURs as established in GVP Module VII as follows:
- within 70 calendar days of the data lock point (day 0) for PSURs covering intervals up to 12 months (including intervals of exactly 12 months); or
- within 90 calendar days of the data lock point (day 0) for PSURs covering intervals in excess of 12 months;
- the timeline for the submission of ad hoc PSURs requested by competent authorities will be normally specified in the request, otherwise the ad hoc PSURs should be submitted within 90 days of the data lock point.
The deadline for the submission of PSURs (Day 70 or Day 90 following the DLP) is published in the EURD list. This deadline is legally binding and must be adhered to.
The timetables for the PSUR assessments are published on the EMA website.
- 17. To whom should I submit my PSUR? Rev. September 2014
Information regarding how to submit PSURs can be found on the eSubmission website and in the Introductory cover note to the List of European Union reference dates and frequency of submission of Periodic Safety Update Reports.
Until the new PSUR repository is available, PSURs should be submitted as follows:
- for CAPs PSURs to be submitted to the European Medicines Agency, the Rapporteur appointed for the procedure and all other Committee Members of the PRAC.
- for NAPs involved in a PSUSA: PSURs to be submitted to all Member States in which the medicinal product has been authorised, the European Medicines Agency and the PRAC Rapporteur appointed for the procedure.
Submission to the European Medicines Agency
From 1 March 2014, the use of the eSubmission Gateway or web client is mandatory for all electronic Common Technical Document (eCTD) submissions through the centralised procedure. The European Medicines Agency no longer accepts submissions on CD or DVD. This applies to all applications for human medicines.
More information on how to register and connect to the Gateway / web Client can be found in the eSubmission website and detailed information on the required naming conventions and file formats can be found in European Medicines Agency eSubmission Gateway: Questions and answers relating to practical and technical aspects of the implementation and the eSubmission Gateway web client: Guidance for applicants. Applicants must not send duplicate submissions electronically or via CD-ROM or DVD as this might lead to delays in the handling of applications.
An automated acknowledgement email is sent from the system confirming whether the submission has passed the relevant technical validation criteria and whether it has been uploaded to the Agency’s review tool and made available via the Common Repository. There is no need to send any accompanying hard media or separate paper cover letter as the cover letter will be in the relevant part of eCTD module 1 in PDF format.
Submission to the (Co-) Rapporteurs and other Committee Members:
If the relevant NCA is not using the Common Repository, one electronic copy should be submitted to the (Co-) Rapporteurs and other Committee Members after the e-submission Gateway/ Web Client confirmation of a technically valid submission to the EMA.
The EMA will check whether the application is correct and complete before the start of the procedure. Any additional information/documentation requested by the Agency prior to the start of the procedure should be equally provided to the (Co-) Rapporteurs and Committee Members, who are not yet using the Common Repository.
For the dossier requirements of the (Co-) Rapporteurs and other Committee members, including delivery addresses where applicable, please refer to the following document: Dossier requirements for Centrally Authorised Products (CAPs).
It is essential that identical eCTD sequences are circulated to Committee Members. Any minor changes that affect the “md5 checksum” will lead to inconsistency and possibly result in future technical invalidity.
Where applications are amended during the Agency’s review, such as e.g. responses to a request for supplementary information or a withdrawal, a new or consolidated eCTD sequence should be provided in order to maintain the eCTD life-cycle.
Submission to the Member State in which a NAP is authorised
For submission requirements for NAPs, regardless whether the PSUSA procedure involves CAPs as well, please follow the CMDh PSUR submission guidance document.
- Dossier requirements for Centrally Authorised Products (CAPs)
- How to submit Periodic Safety Update Reports (PSURs) for EU Single Assessment of substances contained in both Centrally Authorised Products (CAPs) and Nationally Authorised Products (NAPs) to the European Medicines Agency
- CMDh PSUR submission guidance document
- eSubmission website
- Introductory cover note to the List of European Union reference dates and frequency of submission of Periodic Safety Update Reports
- 18. How will my PSUR submission be handled? Rev. December 2014
The PSUR assessment under a PSUSA procedure is as follows, regardless whether it refers to one or more centrally authorised medicinal products, a mix of centrally authorised medicinal products and nationally authorised products, or nationally authorised products only.
The assessment of a PSUR or several PSURs for the same active substance(s) is done by the PRAC or in case of nationally authorised products only by the appointed Member State, respectively. The timelines for assessment are for up to 134 days followed by 67 days of Commission decision making process (if applicable). Upon technical validation by the EMA of the submitted PSUR(s), the following timetable shall apply:
Day Action Day 0 Start of the procedure according to the published timetable Day 60 PRAC Rapporteur’s / Member State preliminary assessment report Day 90 MAH and PRAC members’ / Member States comments Day 105 PRAC Rapporteur’s / Member State updated assessment report (if necessary) Day 120 PRAC recommendation adoption with the final PRAC assessment report Day 134 CHMP opinion / CMDh position (in case PRAC recommends a variation, suspension or revocation of the MA)
The MAH is expected to provide, as applicable, by Day 90:
- responses to the “request for supplementary information” as outlined in the relevant section of the PRAC Rapporteur / Member State PSUR preliminary assessment report,
- comment on the proposed wording (in case the recommendation is a variation),
- propose a wording in case the recommendation is a variation but no exact wording is proposed by the PRAC Rapporteur / Member State,
- provide a justification in case the MAH does not agree with the PRAC Rapporteur / Member State recommendation to vary, suspend or revoke the MA; and/or
- include additional comments or clarification deemed necessary by the MAH
The MAH’s comments should be submitted as per the PSUR dossier submission requirements detailed in the question “To whom should I submit my PSUR?”.
In case the PRAC adopts a recommendation on the maintenance of the marketing authorisation, there is no requirement to transmit such recommendation to the CHMP or CMDh and the procedure ends with the adoption of the PRAC recommendation.
In case the PRAC recommends any regulatory action i.e. variation, suspension or revocation of the marketing authorisation, the PRAC recommendation will be transmitted to the CHMP if it includes at least one CAP or to the CMDh if it includes only NAPs. At its next meeting following the PRAC recommendation, the CHMP or the CMDh, as applicable, will adopt an opinion or a position, respectively. Subsequently, where the procedure includes at least one CAP, the Commission will adopt a decision to the MAHs for the centrally authorised products and, as applicable, to the competent authorities of the Member States for nationally authorised products. Where the procedure includes only NAPs, the procedure ends with the CMDh position in case of consensus and in case of a majority vote, the CMDh position will be followed by a Commission decision to the Member States. For further details on the procedural aspects of the EU PSUSA for NAPs only, please refer to the relevant CMDh SOP.
The outcome of the PSUR assessment results in a legally binding decision or CMDh position and in case of any action to vary, suspend or revoke the marketing authorisations, this should be implemented in a harmonised and timely manner for all products within the scope of the procedure across the EU.
Amendments to the SmPC, package leaflet and labelling as a result of the PSUR assessment are implemented without subsequent variation submission for centrally authorised products and through the appropriate variation at national level for nationally authorised products (including those authorised through the mutual recognition and decentralised procedures).
The Agency publishes the outcome of a PSUR procedure for the CAPs and will publish as well systematically the outcome for NAPs as of September 2014.
For further guidance on the variation to submit to implement the outcome of a single PSUR procedure, please refer to question “How can I apply for the update of the product information after the outcome of a single PSUR procedure?”.
- 19. How is the CHMP opinion structured and which annexes need to be translated? Rev. December 2014
The CHMP Opinion or CMDh position on a PSUR procedure recommending variation to Marketing Authorisation includes the following annexes:
- Scientific Conclusions and grounds recommending the variation to the terms of the Marketing Authorisation and,
- Amendments to the product information and for centrally authorised products, the full product information (Summary of Product Characteristics, Labelling and Package Leaflet, in English);
- Condition to the Marketing Authorisation, if applicable.
The CHMP Opinion on a PSUSA procedureconsists of the following annexes, as applicable:
- Annex A of CAPs
- Annex B for CAPs: includes Annexes I, II, III and IV (scientific conclusions) for each CAP
- Annex C for NAPs: includes Annex I (Scientific Conclusions), Annex II (Amendments to the product information ) and, as applicable, Annex III (conditions to the marketing authorisation)
All the above Annexes to the CHMP Opinion or CMDh position require to be translated in all EU languages.
- 20. What fee do I have to pay? NEW September 2014
The EMA will levy a fee for the assessment of PSUR(s) as of 26 August 2014.
For the PSUR assessment involving only one Marketing Authorisation Holder the total amount of the fee will be levied on that Marketing Authorisation Holder.
For the PSUR assessment under a PSUSA procedure involving more than one Marketing Authorisation Holder, the total amount of the fee will be divided among all the Marketing Authorisation Holders concerned proportionately to the number of chargeable units.
The Marketing Authorisation Holders concerned will be established on the basis of the obligation to submit the PSUR(s) and not on the basis of the actual PSUR submission(s) received by the EMA.
The total of chargeable units in the procedure will be identified from the Art. 57 database. The share payable by each marketing authorisation will be calculated by the EMA. In this respect, an advice note will be sent three months prior to the start date to the relevant QPPVs in order to ensure the accurate identification of the chargeable units for the products involved in the procedure. At start of the procedure, the invoice will be sent to each Marketing Authorisation holder with the relevant chargeable units calculation. The fee will be due to the EMA within 30 calendar days from the date of the invoice.
For Marketing Authorisation Holders already qualified as an SME (i.e. micro-, small- or medium-sized enterprise) by the EMA or for those that will send a SME declaration in advance of the start date or by the latest after 30 days of the invoice date, the fee will be reduced (small- or medium-sized enterprise) or waived (micro-sized enterprise).
The EMA will also publish further guidance on how the fees will be calculated and collected.
- 21. How can I know about the outcome of a PSUSA procedure? Rev. December 2014
For products which were not part of the PSUSA procedure such as generics (under Art 10(1) and well established use (under Art 10a), MAHs should update the product information according to the outcome of the PSUSA procedure through a default type IB variation C.I.3.z, unless the MAH submitted data for assessment, in which case it would be a type II, C.I.3.b.
For nationally authorised products which are part of the PSUSA procedure, please refer to the CMDh website (Question&answers, Pharmacovigilance legislation) for further guidance on the appropriate implementing variation to submit to the National Competent Authorities of the Member States where the concerned products are authorised.
Information on the outcome of centrally authorised medicinal products is made available in the European Public Assessment Report (EPAR) page of the relevant medicine.
Information on the outcome of the EU single assessment of PSURs involving nationally authorised medicinal products will be made available on the EMA web page under Home/Find medicine/Human medicines/PSUSA until the EU web portal if fully functional.
- 22. Can PSURs still be submitted with renewal application? Rev. March 2013
PSURs, PSUR addendums, summary bridging reports and line listings should no longer be submitted as part of a renewal application. The clinical overview submitted in the renewal application should include relevant information to support the benefit-risk re-evaluation of the medicinal product. Please refer to the guideline on the processing of renewals in the centralised procedure.
- 23. Who should I contact if I have a question when preparing my application? NEW September 2014
If you cannot find the answer to your question in the Q&A when preparing your application, please contact us using the following email address: PSURquery@ema.europa.eu
The Agency aims to respond to your query within 5 working days. To help us deal with your enquiry, please provide as much information as possible including the name of the product in your correspondence.
The above email address is only applicable when you have a pre-submission query. A dedicated Procedure Manager (PM) will be assigned to the procedure once your application has been validated. You will be able to contact this PM throughout the procedure.