EU enlargement is a progress toward harmonisation of marketing authorisations of medicinal products in the European Union and European Economic Area. Community pharmaceutical legislation fully harmonises the standards for quality, safety and efficacy of a medicinal product, making any authorisation granted by one Member State generally recognizable by the other Member States. Starting from July 1st 2013, Croatia will be fully part of this system, making easier for the Companies a full regulatory harmonisation in the European Territories
European Union (EU) has progressively enlarged throughout the last decades. Successive accessions have seen the number of members gradually increase from the original six to twenty seven. On 9 December 2011 leaders from the EU and Croatia signed the accession treaty, so that Croatia will become the 28th EU member country on 1 July 2013. Starting from that date, medicinal products market in Croatia will be regulated according to Europan Union laws. For marketing Authorisation of medicinal products, procedures will be harmonised with the Directive 2001/83/EC of the European Parliament and Council. The general basic rule concerning accession, is that HALMED, the Croatian Medicines Agency, has been required to examine whether national marketing authorisations issued prior to accession comply with all requirements of EU legislation on pharmaceutical products (Acquis communitaire): they must be compliant at the accession date. For a limited number of medicinal products listed in the Treaty annex, Croatia has a derogation clause allowing to delay the upgrade after the accession, at the time of renewal or within four years from the date of accession, whichever is earlier. Only these products could provisionally stay on the market, with an authorisation not compliant with EU law. All the other had to submit an application for dossier upgrading to HALMED within 28 February 2013, and upgrading must be concluded within 30 June 2013. The national marketing authorisations granted under national law before accession and not covered by the derogation as well as every new marketing authorisation shall, as of the date of accession, be in compliance with Directive 2001/83/EC.
Medicinal products authorised by the Community through Centralised procedure
Community marketing authorisations of the centrally authorised products extend automatically to Croatia on July 1, 2013. The Marketing Authorisation Holders of products already authorised in the European community have to provide translations of the product information in Croatian and should wait that the product information linguistic review (PALC) is completed before putting the medicine on the Croatian market. As a consequence, in case that a product authorised in Europe through centralised procedure was already marketed in Croatia approved through national procedure prior to the accession, its national marketing authorisation in Croatia will cease to be valid at the accession.
Mutual Recognition and decentralised procedure
Croatia can be included in an mutual recognition procedure (MRP) or in a decentralised procedure (DCP) from the date of Accession, thus 1st July 2013 is the first date that a Mutual Recognition or Decentralised procedure application can be submitted to Croatia as Reference Member State (RMS) or Concerned Member State (CMS). The only exception are products authorised in Croatia, covered by derogation period: they cannot benefit from the MRP procedure until their dossiers are upgraded to be in line with Directive 2001/83/EC. For products authorised in the old Member states via the Mutual Recognition (MRP) or Decentralised (DCP) procedure, or via the purely national procedure, a marketing authorisation application within the framework of the Mutual Recognition Procedure can be submitted to the national competent authorities in order to obtain a marketing authorisation in Croatia Specific rules, related to article 18 of Directive 2001/83, have been defined for marketing authorisation granted in Croatia before accession,: as a general rule when a product is authorised in a specific UE Country, new marketing authorisation in any other EU Country cannot be done on a national basis, but the mutual recognition procedure must be used, to recognise the same marketing authorisation already granted in another member State. This rules have been clarified in relation to marketing authorisation granted in Croatia before accession. In fact it has been clarified that for national MAs in Croatia based on a dossier which is in line with Acquis Communautaire, if the applicant wishes to start a mutual recognition procedure with different name from the name of the medicinal product authorised nationally in Croatia, is it possible that a marketing authorisation granted after completion of the repeat use procedure coexists with the national marketing authorisation granted in Croatia prior to 1st July 2013. For national Marketing Authorisations (MA) in Croatia based on a dossier which is not in line with Acquis Communautaire, is it possible to upgrade the registration dossier and at the same time start a DCP procedure in the EU for the same medicinal product keeping the national authorisation in Croatia valid. In this case the Acquis communautaire ,s condidered as a new procedure. It has also been clarified that if the same medicinal product is authorised in one of the EU countries and was authorised in Croatia prior to the accession, this does not automatically trigger start of MRP procedure. Croatia was a Country that had already signed the New Collaboration Agreement between Drug Regulatory Authorities in Central and Eastern European Countries (nCADREAC). Applicants for national marketing authorisations in Croatia had in the past the possibility, on a voluntary basis, to apply for National marketing authorisations in Croatia through the nCADREAC procedure, a kind of recognition of marketing Authorisations already granted in EU Countries, with harmonisation of Summary of Product Characteristics (SmPC), Product Information Leaflet (PIL), labelling and documentation to those of the corresponding medicinal products authorised in the EU Member States. These national marketing authorisations already granted in Croatia, after accession have the possibility to conduct a repeat use MRP within a shorter timeframe (30 days) if the MAH wishes to add its national MA granted before the date of accession into an existing MRP involving other EU Countries. Of course the marketing authorisation holder in Croatia cannot be completely independent from the Marketing Authorisation holder of the product in the old member state, because it is not possible to have independent Marketing Authorisation holders being part of the same MR/DC procedure. Agreement means that Croatia can accept the current SmPC, labelling and package leaflet in the repeat use without any comments and is therefore prepared to grant a marketing authorisation. Specific rules have been defined in case products approved in Croatia through the simplified CADREAC/nCADREAC procedure have different assembly and batch release sites from those approved in the “old” member state.