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 the Regulation (EC) No 726/2004 and the Directive 2001/83/EC.

Work sharing and EURD List

In order to increase the shared use of resources between competent authorities in Member States, the EU PSUR single assessment for medicinal products (referred also as PSUSA) was established.

The EU PSUR single assessment applies for different medicinal products containing the same active substance or the same combination of active substances authorised in more than one Member State and for which the frequency and dates of submission of PSURs have been harmonised in the list of EU reference dates (also referred to as EURD list) which is published by the EMA and may be accessed from EMA PSUR webpage).

During the PSUSA procedure, submitted PSURs will be jointly assessed by an appointed reference Member State and the PRAC 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.

The EU PSUR single assessment and the subsequent PRAC recommendation can apply to:

• PSURs of centrally authorised product(s;
• PSURs of any mix of centrally authorised products (CAPs) and nationally authorised products (including through the mutual recognition and decentralised procedures;
• PSURs of nationally authorised products (NAPs).

For purely nationally authorised medicinal products, containing substances or combination of actives substances not included in the EURD list and for which no PSUSA procedure has been established, the assessment of the PSURs will remain at national level. 

National PSUR assessments in Malta include a review of PSUR periodicity. A national decision to extend routine PSUR submission frequency (i.e a 3-yearly PSUR cycle) to more than 3 years may be taken for products which have been authorised for more than 10 years and for which no outstanding safety issues remain after assessment. This is a simplification measure.

A list of products authorised in Malta with active substances or active substance combinations not in included in the EURD list and for which PSUR submission is required is available here.

The amended Directive 2001/83/EC waives the obligation to submit PSURs routinely for:

• Generic medicinal products (authorised under Art 10(1)),
• Well-established use medicinal products (authorised under Art 10a),
• Homeopathic medicinal products (authorised under Art 14)
• Traditional herbal medicinal products (authorised under Art 16a),

For such products, PSURs shall be submitted only when the EURD list (see section 10.2 above) requires such submissions or where there is a condition in the marketing authorisation or when a PSUR is requested by the Medicines Authority on the basis of concerns relating to pharmacovigilance data or due to the lack of PSURs for an active substance after its authorisation.

Holders of authorisation under Art 126a of Directive 2001/83/EC are not subject to the obligation to submit PSURs with regards to such authorisation. Parallel importers do not qualify as MAHs, and therefore they are not subject to the obligation to submit PSURs.

Each marketing authorisation holder is responsible for submitting PSURs for its own products and should submit PSURs to the European Medicines Agency (via the centralised PSUR repository) 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.

For information refer to GVP Module VII Periodic safety update report

How to Submit

Marketing authorisation holders are required to submit all PSURs in the EU to the central PSUR repository.

As of 13 June 2016, the use of the PSUR repository is mandatory for both centrally and nationally authorised medicines whether PSURs are submitted for assessment within the context of the PSUSA or PSURs are submitted for assessment during purely national assessment procedures for NAPs not listed in EURD list.

This means that MAHs should no longer submit PSURs to the Malta Medicines Authority directly but should use the eSubmission Gateway/ Web Client. For active substances not included in the EURD list, the MAH should submit the PSUR directly to the PSUR repository, using the non-EU single assessment functionality, via the eSubmission Gateway.

 For more information and resources please visit the eSubmission website.

Alternative mechanisms such as signal management and emerging safety issues channels should be used to communicate relevant new safety information to regulatory authorities (refer to GVP Module VI and Module IX).

It is the responsibility of Marketing Authorisation Holders to ensure that their product information is kept up-to-date in line with Article 16(3) of Regulation (EC) No 726/2004/Article 23(3) of Directive 2001/83/EC by submitting the appropriate variations taking account of the current scientific knowledge, which includes the conclusions of the assessment and recommendations made by the EMA and National Competent Authorities.

Fees for national PSURs and PSUSAs

Procedure based fees for single assessment of periodic safety update reports (PSUSA) are calculated by and are payable to the EMA. For further information on EMA fee for PSUSAs refer to https://www.ema.europa.eu/en/human-regulatory/overview/fees/pharmacovigilance-fees-payable-european-medicines-agency

The fee for assessment of national PSURs is Euro 2,300. Fees for assessment of national PSURs are paid to the Malta Medicines Authority. For further information on fees and methods of payment please refer to http://medicinesauthority.gov.mt/productfees.

Marketing Authorisation Holders shall abide by the standards on pharmacovigilance* (including payment of fees charged for post-authorisation activities) as codified in article 31A of the Medicines Act of 2003. Any person who fails to comply with the provisions of articles 31A shall be guilty of an offence and shall, on conviction, be liable to penalties as per article 99 of the Medicines Act of 2003.

With respect to national PSUR assessments; a copy of the proof of payment should accompany the PSUR submission and is a submission validation requirement. To facilitate the validation process and proceed to the PSUR assessment please submit the proof-of-payment to psur.medicinesauthority@gov.mt or it may be included in the PSUR dossier submission under m1\eu\10-cover\mt.

Further Information

For further information on PSURs and the EURD list refer to the EMA PSUR webpage.

For more information on the PSUR repository’s mandatory use refer to the Periodic Safety Update Report (PSUR) repository mandatory use: questions and answers document published by EMA. The format and content of PSURs are described in detail in GVP Module VII Periodic safety update report.