Medicinal Products

Instructions for Variation Applications Following the Outcome of the PSUSA Procedure

In accordance with Article 50 of the Medicinal Products Act (Official Gazette no. 76/13, 90/14, 100/18, 136/25) when a PSUSA (Periodic safety update report single assessment) procedure leads to a variation of marketing authorisation, marketing authorisation holder (MAHs) for the medicinal products containing the same active substance or combination of active substances as those covered by the PSUSA procedure, should submit a variation to align the Product Information with the outcome of the PSUSA assessment. This is required even if their product (generic medicine or a medicine authorised on the basis of well established use) was not in the direct scope of the PSUSA procedure.

• PSUSA CAPs and PSUSA CAPs/NAPs

The outcomes of the PSUSA procedures for centrally authorised medicinal products (PSUSA CAPs), and those covering both centrally and nationally authorised medicinal products (PSUSA CAPs/NAPs), are published by the European Commission (EC).

For NP/MRP/DCP medicinal products included in the PSUSA CAPs/NAPs procedure, MAH should submit a variation application to HALMED, within 10 days after the Commission Decision.

For generic medicines and other medicines which are not in direct scope of the PSUSA procedure, MAH should submit a variation application to HALMED within 60 days after the Commission Decision.

• PSUSA NAPs

For a PSUSA procedure involving nationally authorised medicinal products (PSUSA NAPs), the deadline for submitting a variation application for NP/MRP/DCP medicinal products is specified in the document "CMDh Scientific conclusions and grounds for the variation, amendments to the Product Information and timetable for the implementation", section "Annex III. Timetable for the implementation of this position”. On the EMA website, in the section Medicines/Download Medicine Data/Periodic safety update report single assessments (PSUSAs), link here, excel table with PSUSA outcomes is available for NP/MRP/DCP medicinal products.

Variations connected to outcome of the PSUSA procedures should be classified in accordance with Guidelines on the details of the various categories of variation, on the operation of the procedures laid down in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use, and on the documentation to be submitted pursuant to those procedures C/2025/5045.

Changes in Summary of product characteristics (SmPC), Package leaflet (PL) and labelling consequential to PSUSA outcome should be submitted as

• Type IA_IN, C.3.a - Implementation of the agreed wording
• Type IB, C.3.b - Implementation of the agreed wording that requires additional minor assessment
• Type II, C.3.c - Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH

More information regarding variation applications are available on CMDh website in section Questions & Answers/Variations at CMDh/Questions&Answers/Variations.

Information regarding the widening of PSUSA outcome (e.g. when a procedure covering mono-component products is expanded to include fixed-dose combinations) should be regulatory monitored here.

More information about PSUR and PSUSA procedure is available on the HALMED website, i.e. here (in Croatian).

The table below provides information on PSUSA procedure outcomes after 1/1/2020 that require variation application and relates to the medicinal products authorised in Croatia. The outcome of the PSUSA procedure is available in English and in Croatian language (the drop down menu Available languages).
The outcomes of the previously finalised PSUSA procedures are available on the EMA or EC website.