“A Periodic Safety Update Report is a Pharmacovigilance document which is intended to provide an evaluation of a medicinal product’s risk-benefit balance at specified post-authorisation time points.
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What is Periodic safety update reports (PSURs)?
Periodic safety update report (PSUR) provides a periodic and complete assessment of the worldwide safety data of marketed drug.
The objective of the PSUR to provide a systematic and important review of the product’s risk-benefit balance, taking into account new or evolving safety information in the sense of combined risk and benefit information.
Marketing authorisation holders (MAHs) are legally required to submit PSURs, in line with Regulation (EU) No 1235/2010, Directive 2010/84/EU and Commission Implementing Regulation (EU) No 520/2012.
The Guidelines on Good Pharmacovigilance Practices (GVP) Module VII offers guidance on the planning, submission and evaluation of PSURs. This format is a legal necessity for both NAPs and Centrally Approved Goods (CAPs).
Who should submit PSURs?
As of 13 June 2016, MAHs are expected to use the eSubmission Gateway/ Web Client to upload all PSURs in the EU to the central PSUR repository.
The 2010 legislation introduces the EU single assessment principle where a substance is approved in more than one Member State.
The European Medicines Agency maintains a list of EU reference dates and frequency of submission of PSURs (EURD list) for the active substances found in medicinal products in the EU and is constantly updated.
For more information about how to use the repository about PSUR, see:
PSUR repository mandatory use: questions and answers
Marketing Authorisation Holders (MAHs) are required in order to submit PSURs according to the data lock points published in the EURD list. For such items the law provides derogation for regular PSUR reporting. For medicinal products approved under the following Articles of Directive 2001/83 / EC, routine PSUR reporting is not necessary unless there is a particular condition in the authorisation or is otherwise indicated in the EURD list:
• Article 10.1 generics
• Article 10.a well-established use
• Article 14 homeopathic medicines
• Article 16a traditional herbal medicines
Further information on GVP and the EURD list may be found on the EMA’s eSubmission website. Please note that the EURD list is a living document to be updated whenever the PRAC, the CHMP or the CMDh considers necessary in response to the emergence of appropriate new safety details, newly approved substances and requests received from MAHs. Where applicable, substances may be added or removed. MAHs should therefore maintain an awareness of the current status of the list which is reviewed on a monthly basis.
Submission requirements and EU reference dates: the EURD list
MAHs for active substances and combinations of active substances that are subject to assessment at EU level must submit the relevant PSURs according to requirements set up in the list of EU reference dates (EURD) list:
The list does not include substances assessed at national level, although their PSURs must nonetheless be submitted via the PSUR repository. For these active substances, the frequency of submission is established at national level. For more information, see:CMDh best practice guide
Additional information for MAHs on changes to submission of the PSURs for human medicines is available here: PSUR repository mandatory use: Q&A
The EURD list provides the following information for each active substance/combination it contains:
- frequency of PSUR submission;
- data lock point;
- submission date;
- requirements for the submission of PSURs for generic, well-established use, homeopathic and traditional herbal products.
The EURD list is a legally binding document and MAHs are legally responsible for complying with its requirements. The list overrules the ‘standard’ PSUR submission cycle and any conditions related to the frequency of PSUR submission included in a marketing authorisation.
EMA updates the EURD list every month, following adoption by the Committee for Medicinal Products for Human Use (CHMP) and Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), after consultation with the Pharmacovigilance Risk Assessment Committee (PRAC).
Any amendment to the EURD list becomes effective six months after its publication.
For more information on the EURD list and answers to frequently-asked-questions, see the following document:
- extract of the relevant active substances/combinations from the Article 57 database for which the addition/amendment is requested.
EMA encourages stakeholders to carefully consult with the introductory cover note prior to submitting an application. Due to the high volume of requests and the necessary processing time, there may be some pause until EMA can react.
All PSURs should be submitted to the PSUR repository using the eSubmission Gateway/Web Client: http://esubmission.ema.europa.eu/esubmission.html
Details about the registry, how to register and multimedia tutorials for MAHs on how to submit a PSUR as well as the proper electronic formats can be found on the PSUR registry web pages of EMA. here: http://esubmission.ema.europa.eu/psur/psur_repository.html
Assessment of PSURs
PSURs submitted in accordance with the EURD list are subject to EU PSUR single assessment (PSUSA) procedure.
EMA performs PSUSA procedures for evaluating PSURs of medicinal products containing the same active substances or combinations, even though they are subject to separate different marketing authorisations and are approved in various EU Member States. This is aimed at harmonising and strengthening medicine benefit-risk analysis across the European Economic Area.
For more information, see the questions-and-answers below and Periodic safety update report single assessments.
Regulatory Requirement for the Submission of PSUR in different countries
The need for a PBRER to be submitted and the frequency of reporting to regulatory authorities are subject to national or regional regulatory requirements, which generally depend on such factors as the dates of approval, the length of time the product was on the market and the extent of knowledge of the product’s benefit-risk profile.
The PBRER format and content are intended in order to apply to periodic reports that cover reporting periods of 6 months or longer.
If a drug has been put on the market for many years, national or regional regulations may allow the frequency of submission to be expanded to longer time periods, e.g. for products deemed to have an established and acceptable profile or considered to be low risk; however, more regular PBRERs may still be needed in other regions.
Consequently, the following scenarios may be encountered by MAHs:
- PBRERs can be required simultaneously across different regions on 6-monthly, annual, and less frequent submission timetables.
- Changes in reporting frequency may also apply after important additions or changes in clinical use are approved (e.g., new indication[s] and/or new population[s]). In these circumstances, it is possible that the reporting interval will be shortened, even for older products with a previously reduced frequency of PBRER submission.
- A regulating authority can request an ad hoc PBRER.”
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