Interchangeability RulesOfficial Gazette of RS, 102/2010
on more exact demands and procedure for determining interchangeable medicinal products
I. GENERAL PROVISIONS
(Scope of application)
These Rules prescribe more exact demands and procedure for determining interchangeable medicinal products for human use and the method of publication of the list of interchangeable medicinal products (hereinafter: the List).
(Definition of terms)
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:
- Two medicinal products containing the same active substance are considered bioequivalent if they are pharmaceutically equivalent or pharmaceutically alternative and their bioavailabilities (rate and extent) after administration in the same molar dose lie within acceptable predefined limits. These limits are set to ensure comparable in vivo performance, i.e. similarity in terms of safety and efficacy. Bioequivalence is defined in the valid text of the instruction of the European Medicines Agency “Guideline on the investigation of bioequivalence” at the website: http:// http://www.ema.europa.eu/ema/index.jsp? curl=pages/includes/document/document_detail.jsp ?webContentId=WC500070039&murl=menus/ document_library/document_library.jsp&mid= WC0b01ac058009a3dc;
– Two medicinal products are considered pharmaceutically equivalent if they have the same quality and quantity structure of active substances in the same pharmaceutical form and correspond to the same or comparable standards. Pharmaceutical equivalence does not always mean that the medicinal products are bioequivalent, since the differences in excipients or manufacturing procedure may lead to faster or slower dissolution or absorption;
– Pharmaceutically alternative medicinal products are medicinal products containing different salts, esters, ethers, isomers, mixed isomers, complexes or active substance derivatives or differing in terms of pharmaceutical form or strength.
II. MORE EXACT DEMANDS FOR DETERMINING INTERCHANGEABLE MEDICINAL PRODUCTS
(Demands for interchangeable medicinal products)
Interchangeable medicinal products are those bioequivalent, pharmaceutically equivalent or pharmaceutically alternative medicinal products for which the Agency for Medicinal Products and Medical Devices of the Republic of Slovenia (hereinafter: the JAZMP), has issued a decision on interchangeability. The JAZMP may issue a decision on interchangeability in the following cases:
- The probability of the occurrence of clinically relevant differences in efficacy or safety of medicinal products with the same quality and quantity structure of active substances and comparable pharmaceutical form is adequately small or negligible;
- The submitted evidence of common or comparable characteristics of these medicinal products pursuant to the conditions stipulated by the Act and these Rules;
- The discussions of medicinal products take into account the latest findings and results of contemporary biomedicinal science and professional discipline;
- The provisions of marketing authorisation are taken into account and
- The medicinal products have a favourable comparable pharmacovigilance profile or risk-to-benefit ratio.
(Non-interchangeable medicinal products)
Notwithstanding the provision of the previous article, the JAZMP may not issue the decision on interchangeability for:
- 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;
- Medicinal products in pharmaceutical forms with different manners of modified release, if significant differences were found in the characteristics of active substance release;
- Medicinal products with different tools for dosage or use which cause significant differences that could affect the outcome of the treatment, or
- Medicinal products for parenteral use and medicinal products with a narrow therapeutic range and significantly different excipients (e.g.: medicinal products for dermal use, eye).
III. PROCEDURE FOR DETERMINING INTERCHANGEABLE MEDICINAL PRODUCTS
(Initiation of procedure for determining interchangeable medicinal products)
(1) The procedure for determining interchangeable medicinal products can be initiated by the JAZMP:
- Ex officio, after obtaining or amending the marketing authorisation for medicinal product or after obtaining the marketing authorisation through centralised procedure, which obtained from the JAZMP the data needed for entrance on the market or
- Upon the proposal of the 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 (hereinafter: the Proposal) or
- Upon the initiative of the ministry competent for health, extended expert board, for medicinal products lying within its competence and the Health Insurance Institute of Slovenia.
(2) The initiators from the third indent of the previous paragraph are not a party in the procedure.
(Proposal and initiative)
(1) The Proposal must contain evidence on the fulfilment of conditions from Article 3 hereof.
(2) The Initiative must contain explanation, indicating the publicly accessible data from independent professional literature on the fulfilment of conditions from Article 3 hereof.
(Evidence on fulfilment of conditions)
When deciding on interchangeable medicinal products the JAZMP shall take into account the following:
- Data from the documentation on medicinal products,
- Data from the official records on medicinal products,
- Data from the records and publications of the European Medicines Agency or the competent bodies for medicinal products of the European Union Member States,
- Data on medicinal products submitted by the marketing authorisation holder,
- Explanation of the Initiative and publicly accessible data from independent professional literature, if the procedure begins upon the Initiative,
- The latest findings and results of contemporary biomedicinal science and professional discipline, and
- Opinion of the Permanent Medicinal Products Committee.
(2) Marketing authorisation holders, holders of authorisation for parallel imported medicinal products or holders of a favourable opinion from the European Medicines Agency for parallel distribution of medicinal products must submit to the JAZMP, upon its written request, additional data, evidence or explanations needed for determining interchangeable medicinal products.
(Opinion of the Permanent Medicinal Products Committee)
The opinion of the Permanent Medicinal Products Committee must be provided with the grounds of fulfilled conditions for interchangeable medicinal products from the first, third and fifth indent of Article 3 hereof or the first and the second indent of Article 4 hereof.
(Deadlines for issuing the decision and filing appeals)
The JAZMP shall issue a decision on interchangeable medicinal products within 60 days of the beginning of the procedure.
(2) An appeal may be launched against the decision from the previous paragraph within 15 days of serving. The Ministry responsible for health shall decide on the appeal.
(Changing the decision on interchangeable medicinal products)
If the JAZMP establishes that interchangeable medicinal products no longer meet the conditions from Article 3 hereof or if one of the conditions of Article 4 hereof occurs, it shall issue a new decision, stating that a medicinal product no longer meets the conditions to be classified as interchangeable.
IV. PUBLICATION OF THE LIST OF INTERCHANGEABLE MEDICINAL PRODUCTS
(Publication of the list of interchangeable medicinal products)
(1) The JAZMP shall publish interchangeable medicinal products in the list of interchangeable medicinal products (hereinafter: the List) on its website. Interchangeable medicinal products in the List shall be published in groups at Level 5 of the ATC classification, containing the following data:
- ATC code of medicinal product;
- Common name of medicinal product;
- Identification code of medicinal product;
- 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.
(2) The JAZMP shall publish the medicinal product in the list or remove it from the list within five days of issuing the final decision on interchangeable medicinal products or termination of their interchangeability.
(3) The JAZMP shall remove from the list a medicinal product whose marketing authorisation has expired within 18 months of expiry or amendment of the marketing authorisation for a medicinal product, unless it has to be removed immediately in order to protect the public health.
V. TRANSITIONAL AND FINAL PROVISION
(Application of implementing regulation)
(1) 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. 86/10) are also interchangeable pursuant to these Rules, until otherwise determined by the JAZMP.
(2) The JAZMP shall decide on interchangeable medicinal products that have not been included in the list from the previous paragraph prior to the enforcement hereof and that meet the interchangeability conditions within three months of the enforcement hereof.
(Cessation of validity)
With the day of enforcement of these Rules, the Rules on more exact demands and procedure for determining interchangeable medicinal products (Official Gazette of the Republic of Slovenia no. 86/08 and 63/09) shall cease to apply.
(Entry into force)
These Rules shall enter into force on the fifteenth day after their publication in the Official Gazette of the Republic of Slovenia.
Ljubljana, 25 November, 2010
Minister of Health