Generic Medicines in Croatia--Regulatory Aspects and Statistics.

A generic medicine is an equivalent of an originator pharmaceutical product. It contains the same active substance as, is "essentially similar" to, and is therefore interchangeable with, the originator product. The objective of this study was to determine the share of generic medicines of the total received marketing authorization applications in Croatia, and the specificities in the approval of generic medicines with regard to assessments of their quality documentation. We collected the information from the Agency's medicinal products databases. Absolute numbers are shown for the applications for the authorizations of medicines in total and generics in particular in the period from 2005-2009. Data were analyzed using descriptive statistics. The annual number of marketing authorization applications for generic medicines received in Croatia increased from 148 applications in 2005 to 276 applications in 2009. In the period from 2005-2009, the number of applications for the approval of generic medicines accounted for 55% of all submitted applications. More than five generic medicines were approved for the following active compounds: amlodipine, lisinopril, atorvastatin, tamsulosin and omeprazole. In the following years, the number of applications from international manufacturers stagnated, while the number of applications by local manufacturers is on a steady climb, with the exception of 2008. From 2005-2009, an almost continual increase in the number of applications for the approval of generic medicines is evident. The largest number of generic medicines was approved for generic medicines intended for the treatment of cardiovascular disease (amlodipine, lisinopril, atorvastatin). A continual increase of applications from local manufacturers has been recorded. In the approval of these medicines, it is very important to develop a uniform approach to assessing the quality of each medicine, in order to guarantee a high quality product for the patient.

Determination of aqueous stability and degradation products of series of coumarin dimers.

The stability in aqueous solution of five classes of coumarin dimers (I-V, compounds 1-29) was studied by HPLC-MS/MS at various pH values. The relationship between chemical structure and stability is discussed. It was found that dimeric compounds with strong electron withdrawing groups (EWGs) on the α-carbon to the bridging C-atom are stable at all pH values, whereas other derivatives undergo retro-Michael addition at rates which are also affected by the substituents on the aromatic rings. In some cases formation of stable isomers or oxidation products was observed. In order to evaluate their developability and potential for progression to in vivo studies, representative compounds were tested in an in vitro microsomal stability assay.

[Are there counterfeit medicines in Croatia?]. / Ima li u Hrvatskoj krivotvorenih lijekova?

Counterfeit medicines are a growing problem in the world, for their use may endanger patient's health and therefore they pose an enormous public health risk. The manufacture of counterfeit medicines usually involves organised crime groups which place the counterfeit medicines on the market for reasons of profit. Detection and prevention of trade in counterfeit medicines requires close cooperation between medicine regulatory authorities, police, customs, judiciary and pharmaceutical industry. To this day, there have been no recorded cases of counterfeit medicines in the legal supply chain in Croatia. However, medicines without marketing authorisation in Croatia, originating from different countries, could be found on the illegal market. Most frequently, this includes medicines for the treatment of erectile dysfunction such as: sildenafil, tadalafil, vardenafil. In this study, 26 medicines for the treatment of erectile dysfunction, seized in illegal supply chain, were tested. High performance liquid chromatography (HPLC) was used for identification and quantification of active substances in the tested samples. It was determined that 13 out of 26 samples did not comply with declared composition of medicine and quality specification. Furthermore, two samples did not contain declared active substance vardenafil and that may indicate that these medicines are counterfeit.

Granting marketing authorisation for medicines in South East European countries: the point of view of the authority.

European legislation for medicines places the emphasis on an assessment of quality, safety and efficacy during the procedure for the granting of marketing authorisations for medicines, in order to protect patient health. The integrated European regulatory system involves the participation of a network of experts from the agencies of the member states that takes part in the European procedures for the authorisation of medicines. On the way to full membership in the EU, candidate countries and potential candidates have to transpose and implement the European directives for medicinal products; they must also strengthen their scientific and administrative capacities. Croatia acquired good experience in implementing the simplified marketing authorisation procedure for medicines authorised in the EU pursuant to the New Collaboration Agreement between Drug Regulatory Authorities in Central and East European Countries (nCADREAC), which helps it to exchange information and prepare for the implementation of European procedures. However, there are still some provisions to transpose before actual full membership, and also dossier upgrading, in which the marketing authorisation holder has to harmonise its documentation about a medicinal product with the requirements of the directives, if a product already on the market was not previously approved in line with current European legislation. Collaboration with the European Medicines Agency (EMA) through an Instrument for Pre-Accession (IPA) provides candidate countries and potential candidates the opportunity for education and training in some regulatory activities as well as the participation of their representatives as observers in some EMA committees and working groups. Some characteristics of the national regulatory frameworks of the countries of South East Europe in their efforts to achieve harmonisation with EU legislation are presented in this paper.