Medicinal Products

Centrally Authorised Products (CAPs)

Guidelines for marketing authorisation holders

Centrally authorised products (CAPs)

HALMED has received answers from the European Commission and the European Medicines Agency to questions on harmonisation of procedures for centrally authorised products.

1. What will happen with medicines that will not finish the PALC III procedure before the accession?
For those medicines which will not finish the PALC III procedure before accession, will they be allowed to be placed on the Croatian market?
Will the procedure of linguistic checking continue to them after the accession?

The Decisions of the centrally authorised products extend automatically to Croatia on July 1, 2013. However, the Marketing authorisation holders (MAHs) have to provide translations of the product information in Croatian to be in line with the Union legislation. The MAHs should wait that the product information linguistic review (PALC) is completed before putting the medicine on the Croatian market.

More information on the process of PALC III of the extension of the Commission Decision Annexes in the product information in the Croatian language you may find in the following documents:

• Croatian pre-accession linguistic check
• Practical guidance on the extension of Commission Decision Annexes in the new Accession Country language

2. Will all marketing authorisations (MAs) in Croatia that were issued prior to the accession for medicines authorised in the EU through centralized procedure (CP) cease to be valid on the Day 1 of the accession?
Will HALMED withdraw these authorisations or will they automatically be invalid?
Will batches of medicinal products already manufactured according to the national procedure remain on the market until they are sold out?

One of the consequences of the automatic extension of the centrally approved product as of the date of accession is the consequent automatic "inapplicability" of the corresponding national MA. This is an 'automatic process for which DG SANCO does not issue confirmation. In principal, the batches to be place on the market should be in accordance with a valid marketing authorisation only. However, the national competent authority may consider the setting of an appropriate, but not-extensive selling off periods to avoid any shortfalls or stock-outs.

3. What if duplicate* products of centrally authorised generic medicines are authorised in Croatia through national procedure (different name, batch release site and MAH is a daughter company of EU MAH) prior to the accession?
After the accession, can these MAs remain valid nationally, or does Croatia have to withdraw these MAs, or will they automatically cease to be valid?
Is it acceptable to keep batches of nationally approved duplicates of centrally authorised generics on the market until they are sold?

*In the sense of duplicate products we understand medicines which marketing authorisations have been granted upon the same documentation and the marketing authorisation holder in Croatia is linked to the marketing authorisation holder for a generic product authorised centrally in the EU, but both products have different names and batch release sites.

The general rule is that HALMED is required (under Article 6(1) of Directive 2001/83/EC), to examine whether national marketing authorisations issued prior to accession comply with all requirements of EU legislation on pharmaceutical products at the time of accession. There is a list of products subject to transitional arrangements provided by the accession Treaty. Only these products could provisionally stay on the market, even if the authorisation did not comply with EU law. However, as a matter of principle, such a list should not contain generics to centrally approved products for which market exclusivity has not expired.

If these duplicate products (different names, different site, ...) are in line with the Union legislation or are on the list of the Annex V of the Accession Treaty of Croatia, they can stay on the market.

4. According to current Croatian Legislation 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 in the case when the Reference product is authorised by centralised procedure in the EU?
Will the Marketing Authorisation have to be withdrawn if not more than 10+1 years has passed?

Croatia is obliged to upgrade the marketing authorisation dossiers of the generics according to the EU acquis. Croatia has no transitional period for applying the rules of data exclusivity. At the date of accession, the Decisions for the centrally authorised products apply immediately. These products, when used as reference products are protected, during 8 years and not 6 years. So, the MA of these generics should therefore be withdrawn if the reference products are not authorised for more than 8 years or are placed on the market until 10 years (11 years in certain case) have elapsed since the authorisation of the reference product:

• According to the Article 89 of the Regulation (EC) 726/2004, the data exclusivity period of "8+2+1"** refers only to those reference products for which the initial application for granting the marketing authorisation via centralised procedure was submitted from November 20, 2005 onwards.
• For medicinal products for which the initial application for granting the marketing authorisation via centralised procedure was submitted before November 20, the data exclusivity period of 10 years is in effect.

Due to the aforementioned, marketing authorisations for generic products granted on reference products for which the data exclusivity period in the EU (8 or 10 years) has not elapsed, will have to be withdrawn.

Also, if the market exclusivity period of 2+1 years for a reference product has not elapsed, generic products can not be on the market.

**8 years of data exclusivity period (it is not possible to submit an application for a generic product) + 2 years market exclusivity (it is not possible to place the product on the market) + 1 additional market exclusivity period, if one or more new indications with a significant clinical benefit in comparison with the existing treatment have been approved for the reference product within 8 years.