Medicinal Products

Instructions for Variation Applications Following the Outcome of the PSUSA Procedure

When the outcome of the PSUSA procedure leads to a variation of marketing authorisations, marketing authorisation holders (MAHs) for medicinal products containing the active substance covered by the procedure, should submit a variation to align the information of the medicinal product with the outcome of the PSUSA assessment, even if their product was not in the direct scope of the procedure (generic medicine or a medicine authorised on the basis of well established use), conforming with Article 50 of the Medicinal Products Act (Official Gazette 76/13, 90/14 and 100/18) and article 16 of regulation (EC) No. 726/2004.

• PSUSA CAPs and PSUSA CAPs / NAPs

The outcomes of the PSUSA procedures for active substances found only in centrally authorised medicines (PSUSA CAPs), as well as the outcomes of the PSUSA procedures covering nationally authorised medicinal products where centrally authorised products were also involved (PSUSA CAPs/NAPs), are published by the European Commission (EC).

For nationally authorised medicinal products included in the PSUSA CAPs / NAPs procedure, MAHs should submit a variation application to the national competent authority, within 10 days after the Commission Decision in accordance with "Guidelines on the details of the various categories of variations, on the operation of the procedures laid down in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products and on the documentation to be submitted pursuant to those procedures", available here.

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

• PSUSA NAPs

For PSUSA procedures which involve only nationally authorised medicinal products (PSUSA NAPs), a deadline for submitting a variation application is specified in the document "CMDh Scientific conclusions and grounds for the variation, amendments to the Product Information and timetable for the implementation" in section "Annex III. Timetable for the implementation of this position” which is published in all EU languages on the EMA website, i.e. here.

The outcomes of PSUSA procedures, related to medicinal products authorised in Croatia, are available in the table below.

For more information on how to submit a variation application, please refer to the information published on the HMA and CMDh websites available under the following links:

• EMA - Guideline on good pharmacovigilance practices (GVP)
• EMA - PSUR in general
• EMA - Q&A - PSUR
• HMA - Q&A - Pharmacovigilance Legislation
• CMDh - PSUR
• CMDh - Q&A - Submitting a variation application

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

PSUSA procedure outcomes that require variation application

The table below provides information on PSUSA procedure outcomes that require variation application and relates to medicinal products authorised in Croatia. The outcome of the PSUSA procedure is available in English, as well as a translation in Croatian (the drop down menu Available languages). The table contains the outcomes of PSUSA procedures completed after 1/1/2020. The outcomes of the previously completed PSUSA procedures are available on the EMA or EC website, as described in the text which can be accessed here (in Croatian).

The variation should be classified as follows:

• Type IAIN C.I.3.a - implementing the agreed wording in Croatian language in the product information does not require additional adjustments to the latest approved version
• Type IB C.I.3.z - the last approved version of the product information needs to be adapted to the agreed wording which is being implemented
• Type II - implementation of the agreed wording, with the submission of additional data that needs to be evaluated.