VII.A Introduction

Periodic safety update reports (PSURs) are pharmacovigilance documents intended to provide an evaluation of the risk-benefit balance of a medicinal product for submission by marketing authorisation holders at defined time points during the post-authorisation phase.

The legal requirements for submission of PSURs are established in Regulation (EC) No 726/2004, Directive 2001/83/EC and in the Commission Implementing Regulation (EU) No 520/2012 on the performance of pharmacovigilance activities provided for in Regulation (EC) No 726/2004 and Directive 2001/83/EC (hereinafter referred to as IR). All applicable legal requirements in this Module are referenced in the way explained in the GVP Introductory Cover Note and are usually identifiable by the modal verb “shall”. Guidance for the implementation of legal requirements is provided using the modal verb “should”.

The format of PSURs shall follow the structure described in the IR Article 35. This Module provides guidance on the preparation, submission and assessment of PSURs.

The scope, objectives, format and content of the PSUR are described in VII.B.. 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)). The PBRER format replaces the PSUR format previously described in the ICH-E2C(R1). In line with the EU legislation, the report is described as PSUR in the GVP Modules.

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 VII.C., which also covers the single EU assessment of PSURs in VII.C.4.. Details related to the quality system are provided in VII.C.6. and the publication of PSUR-related documents in VII.C.7. as transparency provisions. Each marketing authorisation holder shall be responsible for submitting PSURs for its own products [DIR Art 107b] [REG Art 28 (2)] and should submit PSURs to the Agency (see VII.C.9. for transitional arrangements) according to the following timelines:

• 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); and
• 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 normally be specified in the request, otherwise the ad hoc PSURs should be submitted within 90 calendar days of the data lock point.

It should be noted that detailed listings of individual cases shall not be included systematically [IR Art 34(4)]. The PSUR should focus on summary information, scientific safety assessment and integrated benefit-risk evaluation.

Recital 23 of Directive 2010/84/EU states that the obligations imposed in respect of PSURs should be proportionate to the risks posed by medicinal products. PSUR reporting should therefore be linked to the risk management systems of a medicinal product (see Module V). The “modular approach” of the PSUR described in VII.B.5. aims to minimise duplication and improve efficiency during the preparation and review of PSURs along with other regulatory documents such as the development safety update report (DSUR)1 or the safety specification in the Risk Management Plan (RMP), by enabling the common content of particular sections where appropriate to be utilised interchangeably across different PSURs, DSURs and RMPs.

The amended Directive 2001/83/EC also waives the obligation to submit PSURs routinely for generic medicinal products (authorised under DIR Art 10(1)), well-established use medicinal products (authorised under DIR Art 10a), homeopathic medicinal products (authorised under DIR Art 14) and traditional herbal medicinal products (authorised under DIR Art 16a), [DIR Art 107b(3)]. For such products, PSURs shall be submitted where there is a condition in the marketing authorisation or when requested by a competent authority in a Member State on the basis of concerns relating to pharmacovigilance data or due to the lack of PSURs for an active substance after its authorisation [DIR Art 107b(3)(a) and (3)(b)].

Competent authorities in the Member States shall assess PSURs to determine whether there are new risks or whether risks have changed or whether there are changes to the risk-benefit balance of medicinal products [DIR Art 107d].

In order to increase the shared use of resources between competent authorities in Member States, a single assessment of PSURs should be performed in the EU for different medicinal products containing the same active substance or the same combination of active substances authorised in more than one Member State for which a Union reference date and frequency of submission of PSURs has been established. The EU single assessment can include joint assessment for medicinal products authorised through either national or centralised procedures for marketing authorisation. The Agency shall make available a list of Union reference dates and frequency of submission [REG Art 26(g)] which will be legally binding.

As part of the assessment, it should be considered whether further investigations need to be carried out and whether any action concerning the marketing authorisations of products containing the same active substance or the same combination of active substances, and their product information is necessary.

The Agency shall make the PSURs available to the competent authorities in Member States, members of the Pharmacovigilance Risk Assessment Committee (PRAC), of the Committee for Medicinal Products for Human use (CHMP) and of the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) and the European Commission by means of a PSUR repository [DIR Art 107b(2)].