MINISTRY OF HEALTH - HALMED

1 MINISTRY OF HEALTH . 1802. Pursuant to Article 26, paragraph 7, Article 43 paragraph 9, Article 51, paragraph 3, Article 52 paragraph 5, Article 53 paragraph 6, Article 56 paragraph 3, Article 60 paragraph 4, Article 63 paragraph 6, Article 69 paragraph 4, Article 98 paragraph 5, Article 100 paragraph 4 of the Medicinal Products Act (Official Gazette 76/2013), the Minister of HEALTH hereby issues the ORDINANCE. ON GRANTING MARKETING AUTHORISATIONS FOR MEDICINAL. PRODUCTS. I. GENERAL PROVISIONS. Article 1. This Ordinance lays down the procedure, conditions and documentation required for granting, renewal, revocation, and transfer of authorisations for the marketing of medicinal products in the Republic of Croatia, the contents of the Summary of Product Characteristics, package leaflets, and labelling of medicinal products, registration, form and content of documentation, proof of traditional use and the rules of labelling traditional herbal medicinal products and registration and content of documentation for the registration of homeopathic medicinal products.

2 Article 2. (1) This Ordinance transposes the following directives into the legislation of the Republic of Croatia: 1. directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001, on the Community Code relating to medicinal products for human use (SL L 311, ), 2. directive 2002/98/EC of the European Parliament and of the Council of 27 January 2003. setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components and amending directive 2001/83/EC (SL. L 33/30, 8. 2. 2003.), 3. Commission directive 2003/63/EC of 25 June 2003 amending directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use (SL L 159, 27. 6. 2003.), 4. directive 2004/24/EC of the European Parliament and of the Council of 31 March 2004 on traditional herbal medicinal products (SL L 136, 30. 4. 2004.), 5. directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004.

3 Amending directive 2001/83/EC on the Community code relating to medicinal products for human use (SL L 136, 30. 4. 2004.), 6. directive 2008/29/EC of the European Parliament and of the Council of 11 March 2008. amending directive 2001/83/EC on the Community code relating to medicinal products for human use, as regards the implementing powers conferred on the Commission (SL L 81, 20. 3. 2008.), 7. directive 2009/35/EC of the European Parliament and of the Council of 23 April 2009 on the colouring matters which may be added to medicinal products, 8. directive 2009/53/EC of the European Parliament and of the Council of 18 June 2009. amending directive 2001/82/EC and directive 2001/83/EC, as regards variations to the terms of marketing authorisations for medicinal products (SL L 168, 30. 3. 2009.), 9. Commission directive 2009/120/EC of 14 October 2009 amending directive 2001/83/EC. of the European Parliament and of the Council on the Community code relating to medicinal products for human use as regards advanced therapy medicinal product (SL L 242.)

4 15. 9. 2009). (2) This Ordinance regulates the implementation of the following regulations: 1. Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16. December 1999 on orphan medicinal products (SL L 18, 22. 1. 2000), 2. Commission Regulation (EC) No 847/2000 of 27 April 2000 laying down the provisions for implementation of the criteria for designation of a medicinal product as an orphan medicinal product and definitions of the concepts similar medicinal product and clinical superiority (SL L 103, 28. 4. 2000), 3. Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (SL L. 136, 30. 4. 2004), 4. Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13. November 2007 on advanced therapy medicinal products and amending directive 2001/83/EC and Regulation (EC) No 726/2004 (SL L 324, 10.

5 12. 2007), 5. Commission Regulation (EC) No 658/2007 of 14 June 2007 concerning financial penalties for infringement of certain obligations in connection with marketing authorisations granted under Regulation (EC) No 726/2004 of the European Parliament and of the Council (SL L. 155, 15. 6. 2007), 6. Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products (SL L 334/7, 12. 12. 2008), 7. Commission Regulation (EU) No 712/2012 of 3 August 2012 amending Regulation (EC). No 1234/2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products (SL L. 209, 4. 8. 2012). Article 3. (1) The provisions of this Ordinance shall appropriately apply to all medicinal products for which marketing authorisation applications are submitted in the Republic of Croatia, with certain specifics for the following groups of medicinal products: biological medicinal products, radio-pharmaceuticals and precursors, medicinal products for the treatment of severe and rare diseases (orphan drugs), advanced therapy medicinal products, homeopathic products, traditional and herbal medicinal products.

6 (2) The specific content of the documentation for the groups of medicinal products referred to in paragraph 1, subparagraphs 1-4 of this Article are provided in Annex II which forms an integral part of this Ordinance, while for groups from indents 5-6 are prescribed in Articles 65. 76 of this Ordinance. Article 4. In the sense of the Medicinal Products Act (hereinafter: Act) and this Ordinance, the same medicinal products shall be deemed medicinal products of the same applicant for the granting of marketing authorisation / marketing authorisation holder, having the same quantitative and qualitative composition of active compound and the same pharmaceutical form. Article 5. (1) In preparing the medicinal product dossier, the applicant is obliged to follow the general chapter, special and general monographs of the European Pharmacopoeia. (2) In the preparation of the dossier, the applicant shall take consideration of the guidelines of the European Medicines Agency (hereinafter: EMA), European Commission, Coordination Group for Mutual Recognition and Decentralised Procedure, Human Medicinal Products (hereinafter: CMD(h)) and the Heads of Medicines Agencies (hereinafter: HMA).

7 (3) All significant information on the assessment of the medicinal product, either positive or negative, must be included in the dossier. (4) The dossier should include all important details on incomplete or terminated preclinical or clinical trials relating to therapeutic indications not reported in the dossier. (5) For the purpose of monitoring and assessing the cost to benefit ratio of medicinal products, all new information not contained in the application for the granting of marketing authorisation for a medicinal product and all information on the safety of administration of a medicinal product of the marketing authorisation holder shall be submitted to the Agency for Medicinal Products and Medical Devices (hereinafter: Agency). Article 6. (1) The dossier is submitted with the application pursuant to the provisions of the Act and ordinances adopted pursuant to the Act, and in line with the type of application, group of medicinal product and legal basis for the granting of marketing authorisation for the medicinal product.

8 (2) The dossier from paragraph 1 of this Article is submitted in the form of the Common Technical Document (hereinafter: CTD), in line with the instructions of the European Commission: Volume 2B, Notice to Applicants, Medicinal Products for Human Use, Presentation and Content of the Dossier. (3) The fundamental sections of the CTD are: Module 1: Administrative data and medicinal product information Module 2: CTD summaries Module 3: Quality Module 4: Non-clinical study reports Module 5: Clinical study reports (4) The structure of individual CTD modules is stipulated in Annex I which forms an integral part of this Ordinance. (5) The fundamental principles and requirements for the preparation of Module 1 are prescribed in Articles 77 86 of this Ordinance. (6) The fundamental principles and requirements of the preparation of Modules 2, 3, 4 and 5. are stipulated in Annex I which forms an integral part of this Ordinance. (7) The dossier in electronic form is submitted to the Agency in an electronic form of the CTD with advanced search possibilities through the dossier (hereinafter: eCTD form) or in temporary electronic form of the CTD without advanced search options (hereinafter: NeeS.)

9 Form). (8) Exceptionally, if the applicant does not possess the electronic documentation from paragraph 7 of this Article, the applicant shall be obliged to submit Modules 1, 2, 3, 4 and 5 in written form, and additionally Modules 4 and 5 on an electronic medium. (9) After submission of the dossier in NeeS form, the dossier for all future applications should be submitted exclusively in NeeS or eCTD form. (10) After submission of the dossier in eCTD form, the dossier for all future applications should be submitted exclusively in eCTD form. (11) The dossier is submitted as a photocopy, if this Ordinance does not prescribe the original, or a photocopy certified by a notary public. (12) Exceptionally, the Agency may request the applicant bring the original dossier in for review. (13) The prescribed dossier may be submitted by the applicant in Croatian or in English, except for the documentation which is prescribed by this Ordinance that is shall be submitted in Croatian. (14) The Agency may release further instructions regarding the content, form and manner of submission of dossiers on its website.

10 Article 7. (1) The Agency shall inform the EMA of each denial or revocation of a marketing authorisation for the medicinal product by official duty, every stoppage of marketing a medicinal product or recall of a medicinal product. (2) If the Agency decision on the marketing of a medicinal product impacts human HEALTH in a third country, the Agency shall inform the World HEALTH Organisation therefore, and forward the said notification to the EMA for its information. (3) The report on the assessment of the dossier from Article 42, paragraph 3 of the Act shall be publicly released on the Agency's website. (4) The Agency shall act appropriately within 30 days with a decision of the European Commission passed after arbitration proceedings, which pertains to medicinal products that are approved for marketing or are in the marketing authorisation granting procedure in the Republic of Croatia. II. GRANTING MARKETING AUTHORISATIONS FOR MEDICINAL. PRODUCTS. Article 8. (1) The procedure for granting authorisation is initiated with a written application that is submitted to the Agency pursuant to the provisions of the Act and this Ordinance.