Medicinal Products

Medicinal Products Authorised through the Mutual Recognition procedure (MRP), Decentralised procedure (DCP) and National procedure (NP)

Guidelines for marketing authorisation holders

Medicinal products authorised through the Mutual Recognition procedure (MRP), Decentralised procedure (DCP) and National Procedure (NP)

1. When can Croatia be included in an MRP or DCP?

Croatia can be included in an MRP or DCP from the date of Accession. 1st July 2013 is the first date that a Mutual Recognition or Decentralised procedure application can be submitted to Croatia.

2. Will Croatia have equal rights with current MSs in terms of MRP and DCP? Will Croatia be allowed to be RMS immediately after the accession?

Croatia will have full rights as the current MSs as of 1st July 2013. This applies also to the MRP and DCP, where Croatia can act as RMS or CMS.

3. How will the current Croatian reference medicinal product for the purpose of data exclusivity be handled after Croatian EU accession? If the MA is in line with Directive 2001/83/EC will the years for data exclusivity be counted from the first authorisation in Croatia even before the accession? What if the Croatian reference medicinal product is not in line with Directive 2001/83/EC?

It has been agreed with the CMDh that a reference medicinal product must meet the following cumulative criteria:

  • It should be (or have been) authorised in the European Union; i.e. for medicinal product authorised in countries prior to their accession to the European Union, the date of accession of the country concerned.
  • It must be authorised in accordance with the Acquis Communautaire. This implies that the dossier of the medicinal product has been updated to comply with the Acquis Communautaire.
  • And the relevant data exclusivity period has to be expired.

The starting date for the purposes of counting the period of data protection is therefore linked to the date of authorisation of the reference medicinal product in accordance with the Acquis in the territory of the European Union.

In practice, it means that two scenarios are possible: either a medicinal product was authorized according to the Acquis Communautaire, as of the date of accession, (see a)) or the medicinal product was brought in compliance with Acquis Communautaire in the transitional period following accession (see b)):

  1. For a medicinal product authorised in Croatia before its accession to EU but according to the Acquis Communautaire requirements on MA application (dossier-modules 1-5), the data protection period will be counted as of the date of accession to EU.
  2. For a medicinal product authorised in Croatia before its accession to EU but not authorised according to the Acquis Communautaire at that time, the medicinal product is not eligible to be a reference medicinal product unless it is granted a marketing authorisation according to the Acquis Communautaire in the Croatia (after accession). The data protection period for this medicinal product will be counted as of the date of the marketing authorisation which has been granted in compliance with the Acquis Communautaire.

Nevertheless, until medicinal products authorised in Croatia become eligible to be reference medicinal products, a reference product authorised in another Member State must be identified ("European Reference Medicinal Product") for purpose of generic application. The use of this provision will only be possible if the reference product is out of data protection in the Member State where it is authorised. For further guidance on Data exclusivity and market exclusivity period for reference medicinal products, please refer to section 6, chapter 1 of Volume 2A of "Notice to Applicants".

4. According to current Croatian Law on Medicinal Products (Official gazette, No. 71/07, 45/09 and 124/11), data exclusivity applies to Reference Medicinal Products which were granted marketing authorisation in the Republic of Croatia or any EU Member State not more than six years ago. What will happen with generic medicinal products authorised nationally once Croatia joins the EU - will the marketing authorisation for these products have to be withdrawn if not more than 8 years had passed?

The data exclusivity applying to products authorised in HR before the accession will not change with the accession. If a generic medicinal product was authorised before the accession based on the previously valid Croatian legislation (data exclusivity six years), marketing authorisation for this product does not have to be withdrawn.

5. Croatia has the derogation clause contained in the Accession Treaty. It refers to MAs issued under Croatian law prior to the date of accession and they have to be upgraded to be in compliance with the Acquis at the time of renewal or until four years from the date of accession, whichever is earlier (these products are listed in Treaty Annex).

  1. Can these products benefit from the MRP procedure before their dossiers are upgraded?
    Products covered by this derogation period cannot benefit from the MRP procedure until their dossiers are upgraded to be in line with Directive 2001/83/EC.
  2. For national MAs in Croatia based on the dossier which is in line with Acquis Communautaire, if the applicant wishes to start a repeat use procedure with different name from the name of the medicinal product authorised nationally in Croatia prior to 1st July 2013, is it possible that MA granted after completion of the repeat use procedure coexists with the national MA granted in Croatia prior to 1st July 2013 (products have different names, identical dossiers)? What if the applicant wishes to have the same name of these two products?
    When the product is approved under the MRP, the original national MA may either be withdrawn or the two MAs may coexist. Whether the same name can be used for coexisting MRP and nationally authorised product will depend on the national legislation.
  3. For national MAs in Croatia based on the dossier which is not in line with Acquis Communautaire, is it possible to upgrade the registration dossier and then start a DCP procedure in the EU for the same medicinal product keeping the national authorisation valid without upgrading the dossier (until the deadline defined by the Accession Treaty)? If yes, can the name of the product authorised by this two procedures (Croatian national procedure prior to the accession and DCP procedure after the accession) be the same? What will happen when the MAH upgrades the dossier for the nationally authorised product? Is Croatia obliged to withdraw a national MA when DCP procedure is finished?
    In the situation described above it is possible to start a DCP procedure with the upgraded dossier keeping the national authorisation valid. Nevertheless, the applicant shall be advised to submit the upgraded dossier to the Croatian Agency at the same time when the application for DCP starts. Whether the same name can be used for coexisting DCP and nationally authorised product will depend on the national legislation.

6. What will happen with pending national applications in Croatia for products already approved/pending in another Member State at the date of Accession?

Articles 17(2) and 18 of Directive 2001/83/EC are applicable in this situation. According to Article 17(2) of Directive 2001/83/EC, as amended, where Croatia at the date of accession that another marketing authorisation application for the same medicinal product is being examined in another Member State, Croatia shall decline to assess the application and advise the Applicant that Articles 28 to 39 of Directive 2001/83/EC apply. The Member State, which has already started the examination, will normally be the future RMS.

In the case of Article 18 where the same medicinal product is already authorised, via a national, mutual recognition or decentralised procedure, in a Member State at the date of accession, Croatia shall reject the application, unless it was submitted via the Mutual Recognition Procedure and will inform the MS where the product has been authorised.

As stated under 3.2, chapter 2 of Volume 2A of "Notice to Applicants", differences between the SPC, PIL and labelling approved in one MS and the SPC, PIL and labelling submitted in another MS do not automatically prevent the latter from a MRP. If these differences have no therapeutic implications (no difference in the efficacy and safety profile), i.e. both products have the same qualitative and quantitative composition in active substances (i.e. the same strength) and the same pharmaceutical form, they have to be considered as being the same and the MRP has to be followed.

7. If a medicinal product is authorised through national procedure in Croatia before EU accession and the same product is also authorised in at least one EU Member state, will this product have to be mandatorily included into MRP procedure after Croatian EU accession or will this be voluntarily decided by MAH?

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.

8. Is it mandatory for medicinal products authorised through nCADREAC procedure in Croatia to be included into repeat use procedure (RUP) after the accession of Croatia, or can they remain authorised through a national procedure?

It is not mandatory to start a RUP for products authorised through nCADREAC in Croatia. After the accession, Croatia will continue to independently assess all new documentation for these products if they remain authorised nationally.

9. What will happen with simplified nCADREAC procedures that are still pending in Croatia on 1st July 2013? Is it possible to have a shorter 30-day administrative procedure for them without having to do a repeat use procedure?

No, if the products are to be brought into MR, then a repeat use MRP must be started.

10. How can an applicant benefit from having a product authorised in Croatia via the simplified nCADREAC procedure e.g. shorter timetable for MRP repeat use?

The principal benefit of having used the simplified nCADREAC procedure is the use of a shorter timeframe (30 days) in a repeat use MRP if the MAH wishes to add a national MA granted before 1st July 2013 into an existing MRP and all MS agree with the shorter timeframe. Agreement means that Croatia can accept the current SPC, labelling and package leaflet in the repeat use procedure without any comments and is therefore prepared to grant a marketing authorisation.

11. What is the documentation to be submitted for simplified MRP following nCADREAC procedure? What documentation will RMS send to Croatia?

The principle of CADREAC/nCADREAC procedure was the submission of identical dossier and identical post-authorisation maintenance as in the MRP, as well as the submission of all assessment reports generated within MRP. Therefore the documentation to be submitted by the applicant can be limited to the following:

  • Application form
  • Declaration of MAH that the dossier already submitted in Croatia is identical to the current dossier in RMS
  • Proposed dates for common MRP renewal and PSURs submissions
  • In the case that an application for MA variation of the product concerned is pending in Croatia at the time of repeat use MRP, the explanation should be provided in the covering letter and acceptability of processing the repeat use procedure in 30 days should be pre-discussed with Croatia.

The RMS should send to Croatia the following:

  • Copy of current Product information
  • List of all variations and renewals approved in MRP for the product concerned
  • The common renewal date
  • In case of need Croatia can request the RMS to send any missing variation report or an updated assessment report before the procedure can start.

12. Products approved in Croatia through the simplified nCADREAC procedure may have a different product name or have different pack sizes and will have a different MAH from those approved in the EU. If these products are the subject of a shorter 30-day repeat use MRP, how will these differences be handled?

Different product names in different MSs are acceptable within an MRP. Additional pack sizes should be added to the MR-SPC either before or after the repeat use procedure.

Additional assembly or batch release sites may not be included in the repeat use MRP but should be added by a Type IA variation after the procedure is finished. In relation to continuity of supply to the market, it should be noted that the current MA in Croatia does not need to be withdrawn when a repeat use MRP is started, so that batches may be supplied under that MA during the MRP. It is not possible to have independent MAHs being part of the same MR/DC procedure.

13. Is there an obligation to use the MRP or DCP for a line extension to a product initially approved through a national procedure in Croatia, including products approved using the simplified nCADREAC procedure?

No, independent national procedures can be used for extensions of authorised medicinal products as far as no a priori harmonisation has been achieved.

14. Can it be confirmed that the deadline for preparing/updating the assessment report is 90 days from the moment of official request made by the applicant?

For the steps to be taken in obtaining an assessment report, please consult Chapter 2 of Volume 2A of the "Notice to Applicants". It should be noted that the request for an assessment report or an update of an assessment report occurs after any update of the dossier which may be necessary before starting an MRP. After the dossier has been updated, the applicant makes a formal request to the RMS for an (updated) assessment report, which is provided no later than 90 days after receipt of the request.

15. Will it be possible to export pharmaceuticals manufactured in Croatia to current MSs immediately after Croatia officially joins the EU?

MA holders will be allowed to place medicinal products manufactured in Croatia in other EU Member States provided that the product possesses a valid MA in the Member State where the product should be placed on the market and that the manufacturing site in question is covered by the MA.

16. Will batch release site from Croatia be accepted in the current MS from 1 July 2013? Will it be possible to submit a variation in the current MS before Croatian accession so that Croatian batch release site in the current MS is accepted on Day 1 of Croatian accession?

Batch release site from HR will be accepted in other MSs once the variation to add them to the MA is approved, but the variation cannot be submitted before the date of accession.