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 patien

Synthesis and Anti-inflammatory Activity of Novel Furochromenes

A series of variously substituted furochromenes, hemiacetals 2, acetals 3, and rearranged compounds 4, were synthesized from variously substituted 4-hydroxycoumarins and evaluated in several in vitro assays, inhibition of mast cell degranulation induced by the activation of Fcε receptor type I or calci-um ionophore and leukotriene B4 (LTB4) inhibition. The most active derivatives, 3p and 4p (8-iso-propyl substitution in coumarin ring) and 3r (5-methyl-8-chloro substitution), showed significant inhibition of mast cell degranulation (Fctriggered) and LTB4, and exhibited significant local anti-inflammatory activity in PMA induced ear edema in CD1 mice, with potency equal (compounds 3p and 4p) or better (compound 3r) in comparison with zileuton, a reference drug used. It might be a promising direction for developing novel drugs as potential agents for the treatment of allergies and other inflammatory diseases.(doi: 10.5562/cca2240

Dobra proizvođačka praksa: uloga domaćih proizvođača i nadležnih tijela

In every country, a manufacturer of medicinal products for either human or veterinary use is required to operate in compliance with local legislation effect that they are committed to abide by the same standards. The candidate countries transpose the acquis into their national legislation, including the good manufacturing practice (GMP). Consequently, the local manufacturer is required to strictly comply with GMP and the manufacturing licence, including for medicinal products exclusively intended for export. A vital role is also played by national regulatory authorities, in Croatia by the Agency for Medicinal Products and Medical Devices which issues the manufacturing licence, GMP certifi cate, and the Certifi cate of a Pharmaceutical Product (CPP) and conducts laboratory control of products. GMP inspection is carried out by the Pharmaceutical Inspectorate with the Ministry of Health and Social Welfare. Both authorities are responsible only for human medicines. There are legislative issues not yet harmonised with the acquis, but as a country aspiring for the EU membership, Croatia is expected to demonstrate that its industry and competent authorities are able to conform to current requirements and thus fully adhere to the integrated European regulatory network. Hence the importance of strengthening the institutional capacity of the competent authorities, as insuffi cient resources may have a direct bearing on patients by limiting their access to affordable treatment.U svakoj zemlji proizvođač lijekova za humanu ili za veterinarsku uporabu obavezan je poslovati sukladno lokalnom zakonodavstvu, koje je u EU usklađeno za sve članice koje moraju poštivati jednake standarde. Zemlje kandidati za članstvo ugrađuju europsko zakonodavstvo u nacionalno i na taj način implementiraju dobru proizvođačku praksu (GMP). Sukladno tomu, proizvođač lijeka obvezan je osigurati da se svi proizvodni postupci za lijekove izvode u skladu s dobrom proizvođačkom praksom i proizvodnom dozvolom uključujući i lijekove koji su namijenjeni samo za izvoz. Ovdje je nezaobilazna i uloga nacionalnih regulatornih tijela posebno Agencije za lijekove i medicinske proizvode koja izdaje proizvodnu dozvolu, GMP certifi kate i certifi kate o farmaceutskom proizvodu - lijeku (CPP) te provodi laboratorijsku kontrolu proizvoda. GMP inspekciju provodi farmaceutski inspektorat koji je u sastavu Ministarstva zdravstva i socijalne skrbi. Oba su tijela nadležna samo za lijekove za humanu uporabu. Postoje još neka neusklađena pitanja što se tiče prihvaćanja Pravne stečevine na ovome polju, ali kako je Hrvatska zemlja kandidat za punopravno članstvo u EU, očekuje se da će moći demonstrirati da njezina industrija i nadležna tijela poštuju važeće zahtjeve EU i tako potpuno pristupaju europskoj regulatornoj mreži. Stoga je važno jačati institucionalni kapacitet nadležnih tijela, jer nedostatni potencijali mogu izravno utjecati na pacijente ograničavajući im pristup dostupnim terapijama

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Water for all : Proceedings of the 7th international scientific and professional conference Water for all

The 7th International Scientific and Professional Conference Water for all is organized to honour the World Water Day by the Josip Juraj Strossmayer University of Osijek, European Hygienic Engineering & Design Group (EHEDG), Danube Parks, Croatian Food Agency, Croatian Water, Faculty of Food Technology Osijek, Faculty of Agriculture in Osijek, Faculty of Civil Engineering Osijek, Josip Juraj Strossmayer University of Osijek Department of Biology, Josip Juraj Strossmayer University of Osijek Department of Chemistry, Nature Park “Kopački rit”, Osijek- Baranja County, Public Health Institute of the Osijek- Baranja County and „Vodovod-Osijek“ -water supply company in Osijek. The topic of World Water Day 2017 was "Wastewater" emphasizing the importance and influence of wastewater treatments on global environment. The international scientific and professional conference Water for all is a gathering of scientists and experts in the field of water management, including chemists, biologists, civil and agriculture engineers, with a goal to remind people about the significance of fresh water and to promote an interdisciplinary approach and sustainability for fresh water resource management. The Conference has been held since 2011. About 300 scientists and engineers submitted 95 abstracts to the 7th International Scientific and Professional Conference Water for all, out of which 33 was presented orally and 62 as posters. 47 full papers were accepted by the Scientific Committee. 38 full papers became the part of the this Proceedings while 9 papers were accepted for publication in Croatian Journal of Food Science and Technology and Electronic Journal of the Faculty of Civil Engineering Osijek - e-GFOS

ARE THERE COUNTERFEIT MEDICINES IN CROATIA?

Krivotvoreni lijekovi postaju sve veći problem u svijetu jer ugrožavaju zdravlje pacijenta i javnozdravstveni su rizik. Ovi su lijekovi rezultat dobro organiziranog kriminala koji u svrhu stvaranja dobiti plasira na tržište lažne lijekove. U otkrivanje i sprječavanje trgovine takvim proizvodima uključena su regulatorna tijela za lijekove, policija, carina, pravosudna tijela i farmaceutska industrija. U Hrvatskoj do sada nije zabilježena pojava krivotvorenih lijekova u ovlaštenim lancima opskrbe. Međutim, na crnom tržištu katkad se jave lijekovi koji potječu iz drugih zemalja i koji nemaju odobrenje za stavljanje u promet u Hrvatskoj. Najčešće su to lijekovi za liječenje erektilne disfunkcije: sildenafil, tadalafil i vardenafil. U ovom radu ispitani su uzorci 26 lijekova zaplijenjenih u ilegalnom lancu opskrbe, a koji su namijenjeni za liječenje erektilne disfunkcije. Za kvalitativno i kvantitativno određivanje djelatnih tvari u ispitanim uzorcima lijekova upotrijebljena je metoda tekućinske kromatografije visokog učinka (HPLC). Utvrđeno je da od 26 uzoraka 13 ima odstupanja od deklariranog sastava i sukladno tomu ne udovoljavaju zahtjevima kakvoće. Nadalje, dva uzorka nisu uopće sadržavala djelatnu tvar vardenafil, što upućuje i na mogućnost krivotvorine.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

Regulating Medicines in Croatia: Five-year Experience of Agency for Medicinal Products and Medical Devices

Aim To present the activities of the Agency for Medicinal Products and Medical Devices in the first 5 years of its existence and to define its future challenges. Methods Main activities within the scope of the Agency as a regulatory authority were retrospectively analyzed for the period from 2004-2008. Data were collected from the Agency’s database and analyzed by descriptive statistics. Results The number of issued medicine authorizations rose from 240 in 2004 to 580 in 2008. The greatest number of new chemical and biological entities was approved in 2005. The greatest number of regular quality controls (n = 5833) and special quality controls was performed in 2008 (n = 589), while the greatest number of off-shelf quality controls (n = 132) was performed in 2007. The greatest number of medicine labeling irregularities was found in 2007 (n = 19) and of quality irregularities in 2004 (n = 9). The greatest number of adverse reactions was reported in 2008 (n = 1393). The number of registered medical devices rose from 213 in 2004 to 565 in 2008. Conclusion Over its 5 years of existence, the Agency has successfully coped with the constant increase in workload. In the future, as Croatia enters the European Union, the Agency will have to face the challenge of joining the integrated European regulatory framework

Ružička days : International conference 19th Ružička Days “Today Science – Tomorrow Industry” : Proceedings

Dear colleagues, we are extremely honoured to present to you the Proceedings of the international conference 19th Ružička Days, which was successfully held on September 21–23, 2022, in Vukovar, Croatia, in the hometown town of our famous Croatian scientist and first Nobel laureate, professor Leopold (Lavoslav) Ružička. The main goals of the Conference were to promote excellence, originality and innovation of interdisciplinary scientific research as well as the practical application of the obtained results through collaboration with industry, emphasizing thus the recognizable slogan of the Ružička Days conference: "Today Science – Tomorrow Industry". In addition, the Conference gave the opportunity for meetings, exchanging the ideas, opinions, experiences and cooperation among participants from different working surroundings. It is also important to point out that since 2008, within the international conference Ružička Days, Meeting of Young Chemists has also been held, where high school students, with the help of their mentors, present papers in the field of chemistry, with the aim to direct students and young people to the technical and natural sciences, especially chemistry. In its seventh issue (2011, 2013, 2015, 2017, 2019, 2021) the Proceedings publishes scientific and professional full papers of high quality in the following sections: Chemical analysis and synthesis (10), Chemical and biochemical engineering (3), Food technology and biotechnology (4), Chemistry in agriculture and forestry (1), Environmental protection (9) and 8th Meeting of Young Chemists (3). Full-length papers were subjected to an international review procedure done by eminent experts from the corresponding fields, to whom we express our gratitude, but they were not subjected to linguistic proofreading. On behalf of the Scientific and Organizing Committee of the 19th Ružička Days we cordially thank all the authors, reviewers, participants, lecturers, organizers, especially the international organizers EuCheMS and EHEDG, auspices and sponsors, and all the others who, in any way, supported the Conference and contributed to the preparation of the Proceedings, especially to our highly skilled and committed associates, who have put a lot of effort in the preparation of these Proceedings. At the very end, special thanks to our young, future scientists and their mentors who are faithful participants of the Meeting of Young Chemists of the Ružička Days conference. Enjoy the extremely interesting scientific and professional papers contained in these Proceedings, until the next 20th jubilee of Ružička Days in 2024! We are looking forward to meeting you again in Vukovar! Yours sincerely, Chief Editors Jurislav Babić Vesna Ocelić Bulatović Dajana Kučić Grgi