Types of and Formal Requirements for Applications for Marketing Authorisation of Medicinal Products, a List of Supplementary Documentation, Requirements for Supplementary Documentation, Amount of Remuneration Payable for Professional Assessment of Applications Set out by Types of Application, and the Procedure for Calculation and Payment of Remuneration

Passed 18.02.2005 Annex 28
RTL 2005, 25, 347
Entry into force 06.03.2005

This Regulation is established on the basis of clause 65 (12) 1) of the Medicinal Products Act.
[RTL 2010, 20, 365 – entered into force 24.04.2010]

§ 1.  Scope of application

  This Regulation stipulates the types of applications for marketing authorisation to be submitted to the State Agency of Medicines in the course of applying for marketing authorisation of medicinal products, formal requirements for the applications, a list of supplementary documentation to be attached to the application, requirements for supplementary documentation, amount of remuneration payable for professional assessment of applications set out by types of applications, and the procedure for payment of the said remuneration.

§ 2.  Types of and formal requirements for applications for marketing authorisation of medicinal products

 (1) The types of applications for marketing authorisation of medicinal products are the following:
 1) independent application;
 2) generic application.
[RTL 2009, 34, 445 – entered into force 12.04.2009]

 (2) A generic application shall be submitted in the cases provided in clause 65 (4) 2) of the Medicinal Products Act.
[RTL 2010, 20, 365 – entered into force 24.04.2010]

 (3) The types of independent applications are the following:
 1) an application based on research;
 2) an application based on the published literature or a bibliographic application, which, instead of referring to the results of pharmacological and toxicological tests or clinical trials, refers to the published scientific literature, which indicates that the active substance or substances of the medicinal product have a well-established medicinal use, recognised efficacy and acceptable level of safety;
 3) an application filed for marketing authorisation of a medicinal product containing a fixed combination of active substances used in the composition of authorised medicinal products but not hitherto used in combination for therapeutic purposes;
 4) an informed consent application for a medicinal product which is similar with (with the same quantitative and qualitative composition of active substances and the same pharmaceutical form) and bioequivalent to a medicinal product that has a valid marketing authorisation in Estonia and the marketing authorisation holder of which has informed in writing that the pharmacological, toxicological and clinical data attached to the marketing authorisation holder’s application may be used in connection with the new application for marketing authorisation.
[RTL 2009, 34, 445 – entered into force 12.04.2009]

 (4) The application for marketing authorisation of medicinal products shall comply with the form provided in Annex 1 (medicinal products for human use) or Annex 2 (veterinary medicinal products) to this Regulation. The application for EU marketing authorisation shall be submitted in case of decentralised marketing authorisation procedure. For renewal of the marketing authorisation, an application shall be submitted in the form provided in Annex 3.

§ 3.  Supplementary documentation of the application for marketing authorisation of proprietary medicinal products

 (1) The supplementary documentation of the application for marketing authorisation of medicinal products for human use shall contain the following information:
 1) administrative information: name of the proprietary medicinal product, summary of the product characteristics, package leaflet, draft for the design of the package, production and marketing authorisations granted in other countries;
 2) information on the quality of the proprietary medicinal product: chemical-pharmaceutical and biological data and test results;
 3) safety information: toxicological and pharmacological particulars;
 4) efficacy information: clinical particulars.

 (2) [Repealed - RTL 2005, 105, 1604 – entered into force 21.10.2005]

 (3) In case of an application for a veterinary medicinal product, documentation containing the following information shall, if necessary, be submitted in addition to the information specified in subsection (1) and the documents specified in clauses (2) 3)-5):
 1) a description of the precautions to be taken in the storage of, administration of and disposal of the residue of the proprietary veterinary medicinal product;
 2) a description of the potentially harmful effect of the proprietary veterinary medicinal product on the environment, flora, health of humans or animals;
 3) information on the withdrawal period: in case of medicinal products intended for use on agricultural animals, the applicant shall submit and prove that the maximum residue limits, which are allowed and considered safe for the health of the consumer, of the medicinal product and its metabolites in foodstuffs obtained from animals comply with the requirements of the Council Regulation (EEC) No 2377/90 laying down a Community procedure for the establishment of maximum residue limits of veterinary medicinal products in foodstuffs of animal origin (OJ L 224, 18.08.1990, pp 1–8), and submit the methods for determination of the residues of the medicinal product and its metabolites.

 (4) In addition to the information specified in subsections (1) and (2), the supplementary documentation of the application for marketing authorisation of a radionuclide generator shall contain the following information:
 1) a general description of the system together with a detailed description of the components of the system which may affect the composition or quality of the daughter nucleid preparation;
 2) qualitative and quantitative particulars of the eluate or the sublimate.

 (5) When applying for marketing authorisation of a non-biological medicinal product under the conditions set forth in clause 65 (4) 2) of the Medicinal Products Act, the information contained in Modules 1, 2 and 3 set forth in subsection 4 (2) and the data provided in Module 5 on bioavailability and bioequivalence or other data attesting to the therapeutic equivalence of the medicinal product shall be submitted as supplementary documentation of the application.
[RTL 2010, 20, 365 – entered into force 24.04.2010]

 (6) When applying for marketing authorisation of a medicinal product containing a fixed combination of active substances, the safety and efficacy information shall be broken down by combinations, rather than by active substances.

 (7) When applying for marketing authorisation of a biologically identical proprietary medicinal product, the State Agency of Medicines shall decide on the information required in addition to the data presented in Modules 1, 2 and 3 set forth in subsection 4 (3) in each particular case.
[RTL 2005, 105, 1604 – entered into force 21.10.2005]

 (8) When applying for marketing authorisation of traditional oral, inhalation or external herbal preparations, the supplementary documentation of the application shall include the data presented in Modules 1, 2 and 3 set forth in subsection 4 (2), and an expert opinion on safety.

 (9) When applying for renewal of marketing authorisation, the following shall be submitted as supplementary documentation:
 1) a summary of the characteristics of the proprietary medicinal product, updated by the marketing authorisation holder;
 2) a package leaflet, updated by the marketing authorisation holder;
 3) updated data on the safety and efficacy of the proprietary medicinal product, based on reliable updated information and experience obtained in the use of the proprietary medicinal product;
 4) periodical safety report pursuant to the procedure established on the basis of subsection 78 (7) of the Medicinal Products Act;
 5) conforming applications on any changes in the proprietary medicinal products not previously applied for pursuant to the procedure established on the basis of subsection 77 (3) of the Medicinal Products Act.

(10) When applying for renewal of marketing authorisation of homeopathic preparations, updated data on the safety of the preparation, based on reliable, updated information and experience obtained in the use of the preparation, shall be submitted as supplementary documentation in addition to the data set forth in clauses (4) 2), 4) and 5).

§ 4.  Requirements for supplementary documentation of the application for marketing authorisation of proprietary medicinal products

 (1) The supplementary documentation to be attached to the application for marketing authorisation of medicinal products shall be prepared in Estonian or English. The summary of the product characteristics, package leaflet and draft for the design of the package shall be prepared in Estonian, and submitted both in hard copy and in electronic form.

 (2) The Estonian language requirement for the packaging shall not apply in the following cases where the marketing authorisation holder has submitted the corresponding application to the State Agency of Medicines:
 1) vaccines and radiopharmaceuticals;
 2) proprietary medicinal products used only for the provision of in-patient health care services;
 3) medicinal products subject to medical prescription, if their actual sales or estimated sales are less than 3,000 packages per year;
 4) veterinary medicinal products, if their actual sales or estimated sales are less than 1,000 packages per year.
[RTL 2009, 34, 445 – entered into force 12.04.2009]

 (2¹) The State Agency of Medicines may issue an authorisation for marketing of an authorised medicinal product subject to medical prescription in a packaging prepared in the language of a Member State of the European Economic Area on a temporary basis and in a limited amount, if no other medicinal products with the same active substance and strength are marketed in Estonia, and if guaranteeing a constant supply of the medicinal product is significant in terms of public health.
[RTL 2010, 4, 71 – entered into force 29.01.2010]

 (3) The data to be presented in the supplementary documentation of the application for marketing authorisation of medicinal products for human use shall comply with Annex I to Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use (OJ L 311, 28.11.2001, pp 67–128), as amended by Commission Directive 2003/63/EC (OJ L 159, 27.06.2003, pp 46–94) and Commission Directive 2009/120/EC (OJ L 242, 15.09.2009, pp 3–12), as well as Directive 2004/27/EC of the European Parliament and of the Council (OJ L 136, 30.04.2004, pp 34–57), and be classified as follows:
 1) Module 1: Administrative information;
 2) Module 2: Summaries and overviews;
 3) Module 3: Chemical, pharmaceutical and biological information;
 4) Module 4: Non-clinical reports;
 5) Module 5: Clinical study reports. [RTL 2010, 4, 71 – entered into force 29.01.2010]

 (4) Modules 2, 3, 4 and 5 shall be submitted in electronic form, with hard copies submitted at the request of the State Agency of Medicines. Module 1 may be submitted in electronic form in addition to the hard copy.
[RTL 2009, 34, 445 – entered into force 12.04.2009]

 (5) The data to be presented in the supplementary documentation of the application for marketing authorisation of veterinary medicinal products shall comply with Annex I to Directive 2001/82/EC of the European Parliament and of the Council on the Community code relating to veterinary medicinal products (OJ L 311, 28.11.2001, pp 1–6), as amended by Directive 2004/28/EC of the European Parliament and of the Council (OJ L 136, 30.04.2004, pp 58–84) and Commission Directive 2009/9/EC (OJ L 44, 14.02.2009, pp 10–61), and be classified as follows:
 1) part I;
 2) part II;
 3) part III;
 4) part IV.
[RTL 2010, 4, 71 – entered into force 29.01.2010]

 (6) Part I of the supplementary documentation of the application for marketing authorisation of a veterinary medicinal product shall be submitted in hard copy. Parts II, III and IV shall be submitted in electronic form, with hard copies submitted at the request of the State Agency of Medicines. [RTL 2009, 34, 445 – entered into force 12.04.2009]

 (7) The summary of the product characteristics shall contain the following information:
 1) name of the proprietary medicinal product, followed by the strength of the medicinal product and pharmaceutical form;
 2) qualitative and quantitative composition (the International Nonproprietary Name shall be used in Estonian and Latin);
 3) pharmaceutical form;
 4) clinical particulars: therapeutic indications, posology and method of administration, contra-indications, warnings and precautions for use, interaction with other medicinal products and other forms of interactions, use during pregnancy and breastfeeding, effects on ability to drive and use machines, undesirable effects, overdose;
 5) pharmacological properties: pharmacodynamic properties and pharmacokinetic properties, preclinical safety data;
 6) pharmaceutical particulars: list of excipients, major incompatibilities, shelf life, special precautions for storage, nature and contents of container, special precautions for disposal and handling of the medicinal product;
[RTL 2009, 34, 445 – entered into force 12.04.2009]
 7) name or business name and residence or location of the marketing authorisation holder;
 8) for radiopharmaceuticals, full details of internal radiation dosimetry;
 9) for radiopharmaceuticals, additional detailed instructions for extemporaneous preparation and quality control of such preparation and, where appropriate, maximum storage time during which any intermediate preparation such as an eluate or the ready-to-use pharmaceutical will conform with its specifications;
 10) for proprietary veterinary medicinal products, also information on the animal species to whom the product is intended to be administered; for products to be administered to agricultural animals, also information on the withdrawal period for the animal product;
 11) marketing authorisation number; [RTL 2010, 4, 71 – entered into force 29.01.2010]
 12) date of the first authorisation or renewal of the authorisation; [RTL 2010, 4, 71 – entered into force 29.01.2010]
 13) date of revision of the text.
[RTL 2010, 4, 71 – entered into force 29.01.2010]

 (8) The following particulars shall appear on the package leaflet:
 1) name of the medicinal product, followed by the strength and pharmaceutical form and a notice on whether the medicinal product is intended for babies, children or adults, as well as the name of the active substance where the proprietary medicinal product has an invented name and only contains a single active substance;
 2) the complete qualitative composition of the active substances and excipients and quantitative composition of the active substances, using their common names;
 3) the pharmaceutical forms and their contents by weight, by volume or by number of doses;
 4) the pharmaco-therapeutic group, or type of activity in terms easily comprehensible for the patient;
 5) name or business name and residence or location of the marketing authorisation holder, including the holder of the licence for parallel import and the manufacturer responsible for batch release; in case of the license for parallel import, also the name of the re-packager (if applicable);
 6) therapeutic indication(s), except for indications with respect to which the State Agency of Medicines has decided that dissemination of such information might have serious disadvantages for the patient;
 7) information required for administration of the medicinal product: contra-indications, precautions for use of the medicinal product if necessary, forms of interaction with other medicinal products and other forms of interaction (e.g. alcohol, tobacco, foodstuffs) which may affect the action of the medicinal product, special warnings;
 8) instructions for proper use of the medicinal product: dosage, method of administration, frequency of administration, specifying, if necessary, the appropriate time at which the medicinal product may or must be administered, the duration of treatment, where it should be limited depending on the nature of the product, the action to be taken in the case of an overdose (e.g. symptoms, emergency procedures) or the course of action to take when one or more doses have not been taken, indicating, if necessary, the risk of withdrawal effects;
 9) a description of the undesirable effects which can occur under normal use of the medicinal product and, if necessary, the action to be taken in such a case; express invitation of the patient to communicate any undesirable effect not mentioned in the leaflet to the doctor or pharmacist;
 10) reference to the expiry date indicated on the packaging, and the following information: a warning against use of the product after the expiry date, special storage precautions where appropriate, a warning against certain visible signs of deterioration, if necessary;
 11) the date on which the package leaflet was last revised;
 12) for proprietary veterinary medicinal products, also information on the animal species to whom the product is intended to be administered; for products to be administered to agricultural animals, also information on the withdrawal period for the animal product;
 13) – 15)
[Repealed -RTL 2010, 4, 71 – entered into force 29.01.2010]

 (8¹) The package leaflet shall reflect the results of consultations with target patient groups to ensure that it is clear and easy to use. If no consultations have been carried out, the corresponding justification shall be submitted to the State Agency of Medicines.
[RTL 2009, 34, 445 – entered into force 12.04.2009]

 (9) The list set out in clause (8) 7) shall take into account the use of the medicinal product by children, pregnant or breastfeeding women, the elderly, persons with specific pathological conditions, and, if appropriate, mention the possible effects on the ability to drive vehicles or to operate machinery. A list of excipients that may affect the effects and safety of the medicinal product shall be presented in accordance with Annex VI of the Regulation.

 (10) The draft for the design of the outer packaging and immediate packaging shall be presented under Module 1.

 (11) The following particulars shall appear on the outer packaging, or the immediate packaging if no outer packaging is applied:
 1) name of the medicinal product, including the strength and pharmaceutical form and, if necessary, a notice on whether the medicinal product is intended for babies, children or adults, and, if the medicinal product contains up to three active substances, the names of the active substances in Estonian or Latin;
[RTL 2009, 34, 445 – entered into force 12.04.2009]
 2) qualitative and quantitative composition of active substances in a single dose (tablet, capsule) or per volume or weight unit, depending on the method of administration, using the common names of active substances;
 3) pharmaceutical form and size of packaging, expressed in weight, volume, dosage or unit numbers; [RTL 2010, 20, 365 – entered into force 24.04.2010]
 4) a list of excipients that have a recognised effect, including all excipients of injectable preparations, external preparations or eye preparations;
 5) route of administration and, if necessary, method of administration;
 6) a special warning that the medicinal product must be stored out of the reach and sight of children;
 7) other special warnings, if necessary;
 8) the expiry date in clear terms (month and year in the form mm/yyyy);
 9) special storage precautions, if any;
 10) special precautions for disposal of unused medicinal products or waste materials from medicinal products, if appropriate;
 11) name or business name and residence or location of the marketing authorisation holder, including the holder of the licence for parallel import;
 12) marketing authorisation number;
 13) the manufacturer’s batch number;
 14) in the case of medicinal products not subject to medical prescription, indication and instructions on the use of the medicinal product;
[RTL 2009, 34, 445 – entered into force 12.04.2009]
 15) conditions of dispensing of the medicinal product (medicinal product subject to medical prescription/medicinal product not subject to medical prescription);
 16) in case of veterinary medicinal products, the animal species; in case of agricultural animals, the withdrawal period for the medicinal products to be administered;
 17) in case of a licence for parallel import, the name and address of the manufacturer responsible for batch release and the re-packager (if applicable);
 18) where the appearance of a medicinal product with a licence for parallel import (e.g. colour, scoring) differs from the appearance of a medicinal product imported directly, the outer packaging shall contain the corresponding information.

 (11¹) The outer packaging or the package leaflet may include symbols or pictograms designed to clarify the information specified in subsections (8) and (11) and other information compatible with the summary of the product characteristics, to the exclusion of any element of a promotional nature.
[RT I, 30.11.2010, 3 – entered into force 03.12.2010]

 (12) In addition to the information specified in clause (11) 1), the name and strength of the medicinal product shall be marked in Braille, using the Latin alphabet. Only the name of the medicinal product shall be marked in Braille in case of marketing a medicinal product with a single strength. This requirement shall not apply to radiopharmaceuticals, vaccines and proprietary medical products used only for the provision of in-patient health care services.

 (13) The following particulars shall appear on the immediate packaging (small immediate inner packaging):
 1) name of the medicinal product, including the strength and pharmaceutical form and, if necessary, a notice on whether the medicinal product is intended for babies, children or adults, and, if the medicinal product contains up to three active substances, the names of the active substances;
 2) route of administration and, if necessary, method of administration;
 3) the expiry date in clear terms (month and year in the form mm/yyyy);
 4) the manufacturer’s batch number;
 5) contents of the packaging by weight, volume or units.

 (14) The following particulars shall appear on the immediate packaging (blister or grip-and-tear package):
 1) name of the medicinal product, including the strength and pharmaceutical form and, if necessary, a notice on whether the medicinal product is intended for babies, children or adults, and, if the medicinal product contains up to three active substances, the names of the active substances;
 2) the expiry date in clear terms (month and year in the form mm/yyyy);
 3) the manufacturer’s batch number;
 4) name or business name and residence or location of the marketing authorisation holder, including the holder of the licence for parallel import;

 (15) The information specified in subsections (7), (8), (11), (13) and (14) shall be presented in the form provided in Annex 4 to the Regulation in applying for marketing authorisation of medicinal products for human use, and in the form provided in Annex 5 to the Regulation in applying for marketing authorisation of veterinary medicinal products.

 (16) In the cases stipulated in subsections (7), (8) and (11), the substances provided in Annex 6 to the Regulation shall be specified.

 (17) In applying for renewal of marketing authorisation, the differences between the summary of the product characteristics last approved and the summary of the new product characteristics shall be brought out.

§ 5.  Amount of remuneration payable for professional assessment of applications

 (1) The amount of remuneration payable for professional assessment of applications for marketing authorisation shall be the following:
 1) 1,275 euros per proprietary medicinal product in case of an application for marketing authorisation of a medicinal product for human use specified in clause 2 (1) 1) of this Regulation;
 2) 958 euros per proprietary medicinal product in case of an application for marketing authorisation of a medicinal product for human use specified in clause 2 (1) 2) of this Regulation or an application for marketing authorisation of a veterinary medicinal product specified in clause 2 (1) 1) or 2) of this Regulation;
 3) 639 euros per source country of a proprietary medicinal product, in case of an application for a licence for parallel import;
 4) 511 euros per each subsequent method of administration, pharmaceutical form and strength of a proprietary medicinal product of the same marketing authorisation holder, containing the same active substance;
 5) 958 euros per traditional herbal or homeopathic preparation.

 (2) The amount of remuneration payable for professional assessment of applications for renewal of marketing authorisation shall be the following:
 1) 639 euros per proprietary medicinal product;
 2) 383 euros per each subsequent method of administration, pharmaceutical form and strength of a proprietary medicinal product of the same marketing authorisation holder, containing the same active substance;
 3) 383 euros per traditional herbal or homeopathic preparation.
[RT I 2010, 76, 585 – entered into force 01.01.2011]

§ 6.  Calculation and payment of remuneration for professional assessment of applications

 (1) The State Agency of Medicines shall issue the invoice on the remuneration for professional assessment within 10 days after acceptance of the application for processing.

 (2) The applicant shall pay the remuneration for professional assessment within 40 days after presentation of the invoice.

§ 7.  Entry into force

  Subsection 4 (12) of the Regulation shall enter into force on 1 November 2005.

* Directive 2001/82/EC of the European Parliament and of the Council on the Community code relating to veterinary medicinal products (OJ L 311, 28.11.2001, pp 1–6), Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use (OJ L 311, 28.11.2001, pp 67–128), Directive 2004/27/EC of the European Parliament and of the Council amending Directive 2001/83/EC on the Community code relating to medicinal products for human use (OJ L 136, 30.04.2004, pp 34–57), Directive 2004/28/EC of the European Parliament and of the Council amending Directive 2001/82/EC on the Community code relating to veterinary medicinal products (OJ L 136, 30.04.2004, pp 58–84), Commission Directive 2009/9/EC amending Directive 2001/82/EC on the Community code relating to medicinal products for veterinary use (OJ L 44, 14.02.2009, pp 10–61), Commission Directive 2009/120/EC amending Directive 2001/83/EC on the Community code relating to medicinal products for human use (OJ L 242, 15.09.2009, pp 3–12).
[RTL 2010, 4, 71 – entered into force 29.01.2010]