R U L E S
on more exact demands and procedure for determining interchangeable medicinal products

I. SCOPE OF APPLICATION AND DEFINITIONS
Article 1
(scope of application)
These Rules prescribe more detailed requirements and procedures for establishing interchangeability of medicinal products for human use and the procedure of compiling the list of interchangeable medicinal products
Article 2
(definitions)
In addition to the definitions and expressions delineated in Article 6, of the Medicinal Products Act (Official Gazette of the RS, no 31/06 and 45/08; hereinafter referred to as: the Act), the following expressions shall also be used in these Rules:
- essentially similar medicinal product shall mean a medicinal product with the same qualitative and quantitative composition of the active substance and pharmaceutical form as the reference medicinal product whose bioequivalence with the reference medicinal product has been proved by suitable bioavailability studies. Various salts, esters, ethers, isomers, mixed isomers, complexes or active substance derivatives shall be treated as equal active substance unless they differ considerably in terms of safety or efficacy or both. Different oral forms with immediate release are considered to be the same pharmaceutical forms. Bioavailability studies need not be submitted if so stipulated by the relevant instructions prepared in accordance with the scientific and technical findings published in Eudralex (http://ec.europa.eu/ enterprise/pharmaceuticals/ eudralex/eudralex_en.htm) or the website of the European Medicines Agency (http://www.emea.europa.eu/);
- bioequivalence of two medicinal products is defined in the applicable text of the instructions issued by the European Medicines Agency 'Note for Guidance on the Investigation of Bioavailability and Bioequivalence« CPMP/EWP/QWP/1401/98 (website: http://www.emea.europa.eu/).
II. DETAILED REQUIREMENTS AND PROCEDURES FOR ESTABLISHING INTERCHANGEABILITY OF MEDICINAL PRODUCTS
Article 3
(general requirements)
Interchangeable medicinal products can only be those products for which the body competent for medicinal products establishes, based on available data:
- That the probability of occurrence of clinically significant differences in the efficiency and safety of medicinal products is adequately low or insignificant, taking into account the provisions of Article 4 hereof;
- That the submitted evidence of common or comparable characteristics of medicinal products pursuant to this Act or the regulations adopted on its basis;
- That the documents on medicinal products and the discussions of medicinal products take into account the latest findings and results of biomedicinal science and professional discipline;
- That medicinal products have a favourable pharmacovigilance profile or risk/benefit ratio in accordance with the provisions of Article 5 hereof;
- That these are not medicinal products with a narrow therapeutic window, for a specific therapeutic area or other specific risk that would arise due to interchanging of medicinal products;
- That the permanent committee for medicinal products adopted a positive position regarding interchangeability.
Article 4
(interchangeable medicinal products and bio equivalence or essential similarity)
(1) Medicinal products can be interchangeable due to their established bio equivalence or essential similarity in accordance with the standards and guidelines for establishing bio equivalence or essential similarity.
(2) The body competent for medicinal products may, based on the data on clinical safety and efficiency of medicinal products, impose more or less stringent bio equivalence measures in accordance with the standards and guidelines for establishing bio equivalence or essential similarity. In such cases, it may ask the marketing authorisation holder to provide additional data on clinical safety and efficiency of a medicinal product.
Article 5
(interchangeable medicinal products and data on pharmacovigilance)
(1) Mutually interchangeable medicinal products can only be products with comparably favourable pharmacovigilance profile or risk/benefit ratio.
(2) The body competent for medicinal products may change the decision on interchangeability of medicinal products if the pharmacovigilance profile of interchangeable medicinal products changes to such extent that the change affects the comparability of their risk/benefit ratios.
III. PROCEDURE FOR ESTABLISHING INTERCHANGEABILITY OF MEDICINAL PRODUCTS
Article 6
(establishing interchangeability of medicinal products)
The body competent for medicinal products may establish interchangeability of medicinal products:
- In the scope of procedure for obtaining or changing the marketing authorisation or in the procedure for obtaining marketing authorisation with parallel imported medicinal product, if evidence on essential similarity or bio equivalence is part of the application;
- In the scope of independent procedure for establishing interchangeability.
Article 7
(initiation of procedure for establishing interchangeability)
(1) The procedure for establishing interchangeability of medicinal products is carried out by the body competent for medicinal products:
- Ex officio, based on the data from the documents on medicinal products, official records on medicinal products and records and publications of the European Medicines Agency or the competent bodies of the EU Member States,
- Upon the proposal from the applicant from Article 22 of the Act, or
- Upon the proposal from the applicant from Article 78 of the Act.
(2) The following may also submit the initiative for establishing interchangeability of medicinal products from the first indent of the previous paragraph:
- Ministry responsible for health;
- Expanded expert committee for medicinal products, within its competence;
- Permanent committees for medicinal products of the body competent for health;
- The Health Insurance Institute of Slovenia.
Article 8
(proposal for establishing interchangeability)
(1) The proposal from the second and the third indent of the first paragraph of the previous Article must contain evidence of interchangeability based on the criteria from Articles 3, 4 and 5 hereof.
(2) The body competent for medicinal products may, in the procedures referred to in the first indent of the previous paragraph, obtain from the marketing authorisation holder, the holder of authorisation for parallel imported medicinal products or the holder of a favourable opinion from the European Medicines Agency for parallel distribution of medicinal products, evidence on medicinal product needed for establishing interchangeability.
Article 9
(decision-making process)
(1) The body competent for medicinal products adopts its decisions on medicinal product interchangeability on the basis of the opinion of the permanent committee for medicinal products.
(2) In the process of adopting decisions on medicinal product interchangeability, the body competent for medicinal products may ask the applicant to submit additional data or evidence.
Article 10
(opinion of the permanent Medicinal Products Committee)
(1) The procedure for establishing interchangeability of medicinal products is based on the opinion issued by the Medicinal Products Committee on a case-by-case basis. The opinion must contain the assessment of submitted evidence based on the criteria from Articles 3, 4 and 5 hereof.
(2) Notwithstanding the provisions of the previous paragraph, the permanent committee for medicinal products may, upon its own initiative or upon the initiative of the body competent for medicinal products, issue a general opinion on interchangeability of medicinal products in specific therapeutic areas or interchangeability of medicinal products that could induce special risks.
Article 11
(duration of the procedure)
(1) The body competent for medicinal products shall terminate the procedure for establishing interchangeability of medicinal products which is part of the procedure for obtaining or changing the conditions of marketing authorisation, or the procedure for obtaining marketing authorisation for parallel imported medicinal product within the deadlines specified for such procedures.
(2) The body competent for medicinal products shall terminate an independent procedure for establishing interchangeability of medicinal products within 90 days of receiving a complete application, together with the required evidence.
Article 12
(changing the decision on interchangeability of medicinal products)
(1) The body competent for medicinal products change its decisions on medicinal product interchangeability due to changed evidence on medicinal product interchangeability on the basis of which the previous decision was issued.
(2) The procedure in which the body competent for medicinal products re-establishes the interchangeability of medicinal products is carried out pursuant to the same criteria and procedure as described in Articles 3, 8, 9, 10 and 11 hereof.
IV. PROCEDURE FOR COMPILING THE LIST OF INTERCHANGEABLE MEDICINAL PRODUCTS
Article 13
(list of interchangeable medicinal products)
(1) The body competent for medicinal products shall, as a rule twice a year, issue a Decision on the determination of mutually interchangeable medicinal products list by 15 April in the first half of the year and by 15 October in the second half of the year, which it will publish in the Official Gazette of the Republic of Slovenia and on its website.
(2) The list referred to in the previous paragraph shall contain the following data on medicinal products, classified at the fifth level of the ATC classification:
- ATC code of medicinal product;
- Common name of medicinal product;
- Identification code of medicinal product;
- Proprietary name of medicinal product;
- Strength, pharmaceutical form and packaging of medicinal product;
- Name of marketing authorisation holder or the holder of authorisation for parallel imported medicinal products or the holder of a favourable opinion from the European Medicines Agency for parallel distribution of medicinal products;
- Number and date of authorisation or opinion from the previous indent.
(3) The body competent for medicinal products puts on the list all medicinal products for which the procedure for determining interchangeability in accordance with these rules has been completed on 1 March or 1 September.
Article 14
(removal of medicinal products from the list of interchangeable medicinal products)
(1) The body competent for medicinal products may remove a medicinal product from the list of interchangeable medicinal products on the basis of the decision from Article 12 hereof.
(2) If a decision on the removal of a medicinal product from the list of interchangeable medicinal products could impact the protection of public health, the body competent for medicinal products shall immediately publish such fact on its website and carry out the emergency procedure for adopting the amendment to the Decision on the List of interchangeable medicinal products as soon as possible.
V. TRANSITIONAL AND FINAL PROVISION
Article 15
(application of implementing regulation)
Notwithstanding the provisions of these Rules, it shall be deemed that the medicinal products from the Decision on the List of interchangeable medicinal products (Official Gazette of the Republic of Slovenia no. 52/08) are also interchangeable pursuant to these Rules, until otherwise determined by the body competent for medicinal products.
Article 16
(enforcement)
These Rules shall enter into force on the fifteenth day after their publication in the Official Gazette of the Republic of Slovenia.
No. 72-12/2008
Ljubljana, 25 July 2008
EVA 2008-2711-0035
Zofija Mazej Kukovič
Minister of Health