Traditional Medicines and OTC Products
All about traditional medicines and OTC products in Croatia. Prepared in association with Danijel Pribanić, a leading global law firm, this is an extract from The Pharma Legal Handbook: Croatia, available to purchase here for USD 99.
1. What are the regulatory requirements for traditional, herbal, complementary, or alternative medicines and devices?
Regulatory requirements for traditional herbal or homeopathic medicinal products are regulated by the provisions of Medicinal Products Act and traditional herbal medicinal products are also regulated by Ordinance on the Marketing, Labelling and Advertising of Traditional Herbal Medicinal Products (only for advertising).
The provisions of Medicinal Products Act relating to the placement of a medicinal product on the market, production, classification, advertising, distribution, importation, quality control, pharmacovigilance, suspension of marketing and withdrawal from the market and supervision appropriately applies also to the traditional herbal medicinal products, except if not otherwise provided for by this Act or an ensuing regulation.
The registration of a traditional herbal medicinal product is refused if the data and documents accompanying the motion differ from those required and if one of the following reasons is established:
- the quantitative and/or qualitative composition is not as declared, or
- the indications do not comply with the conditions laid down by Medicinal Products Act, or
- the traditional herbal medicinal product could be harmful under usual conditions of use, or
- the data on traditional use are insufficient, especially if pharmacological effects or efficacy are not plausible on the basis of long-standing use and experience, or
- pharmaceutical quality is not satisfactorily demonstrated.
Agency informs the European Commission, and any other competent authority that may so require, about the decision to refuse the registration of a traditional herbal medicinal product as well as about the reasons behind such decision.
Placing on the market homeopathic medicinal products is subject to the possession of a marketing authorisation granted by the Agency or a decision on enrolment in the register issued by the Agency pursuant to the provisions of this Act and the ensuing regulations.
The provisions of this Act relating to homeopathic medicinal products applies to anthroposophic medicinal products prepared by a homeopathic method, described in the current version of pharmacopoeias being in effect in EU Member States.
A simplified procedure for obtaining marketing authorisation for homeopathic medicinal products, or a register enrolment procedure for homeopathic medicinal products, is conducted for homeopathic medicinal products placed on the market without therapeutic indications.
The enrolment in the register of homeopathic medicinal products is conducted for homeopathic medicinal products complying with the following requirements:
- that they are intended for oral or topical administration;
- that there is no reference to their therapeutic indications or data referring to the indication in the package leaflet or on the product label of the homeopathic medicinal product, and
- that they are sufficiently diluted to guarantee safe use of the medicinal product; in particular, homeopathic medicinal products do not contain more than one part per 10.000 mother tincture, or more than 1/100th of the smallest therapeutic dose of the active substance which would be required for the medicinal product referred in Medicinal Product Act to be dispensed on medical prescription.
In the register enrolment procedure for a homeopathic medicinal product the Agency specify dispensing classification of the homeopathic medicinal product.
The provisions of Medicinal Products Act concerning the product label and the package leaflet appropriately apply to homeopathic medicinal products.
Homeopathic nature of the medicinal product is clearly and legibly indicated on the outer and immediate packaging of the homeopathic medicinal product.
The provisions of Medicinal Products Act concerning advertising of medicinal products also appropriately apply to homeopathic medicinal products.
The provisions of Medicinal Products Act concerning marketing, manufacture, distribution, import, quality control, suspension of marketing and withdrawal from the market and supervision of medicinal products also appropriately apply to homeopathic medicinal products, if not otherwise laid down by this Act.
The provisions of Medicinal Products Act concerning pharmacovigilance also appropriately apply to homeopathic medicinal products with marketing authorisation.
2. Can these traditional, herbal, complementary, or alternative products be advertised directly to the public?
Traditional herbal and homeopathic medicinal products are not subject to medical prescription so they may be advertised to the public.
3. What health, advertising, and marketing claims may be made for traditional, herbal, complementary, or alternative products?
Advertising of traditional herbal and homeopathic medicinal product falls under the same regulation as advertising other medicinal products. Advertising of all medicinal products must meet the general requirements provided by Medicinal Products Act.
When advertising traditional herbal medicinal product the following message has to be contained within the advertisement or notice: “Traditional herbal medicinal product for use for the listed indications based on the experience of long-term use”.
The advertising of a product cannot contain any claim on its medicinal properties unless the product is authorised as a medicinal product or registered as a traditional herbal medicinal product.
The provisions of Ordinance on the Manner of Advertising Medicinal Products regulating manner of advertising medicinal products in general apply appropriately to homeopathic medicinal products.
All claims listed in the advertisements for the medicinal product have to be aligned with the claims from the most recent approved package leaflet and summary of product characteristics of the medicinal product in Croatia.
Advertising on the medicinal product ensures the transfer of true and scientifically proven information on the medicinal product, with the abidance of ethical criteria, for the purpose of the proper and rational treatment of patients, without misleading healthcare professionals to recommend, prescribe or dispense medicinal products and medicinal product users in cases when advertising is permitted towards the population.
When advertising homeopathic medicinal products only the following data may be used:
- the scientific name of a homeopathic source or sources and the indication of dilution using pharmacopoeial symbols; where the homeopathic medicinal product contains two or more homeopathic sources, in addition to the scientific names of the sources, an invented name of the medicinal product may appear on the label;
- the name and address of the holder of the decision of enrolment in the register of a homeopathic medicinal product and, in necessary, the manufacturer’s name and address;
- the pharmaceutical;
- the indication »homeopathic medicinal product without proven therapeutic indications«;
- the method of administration and, if necessary, the route of administration;
- the content of the packaging expressed in weight, volume or units of dosage of the homeopathic medicinal product;
- special storage precautions, if applicable;
- expiry date of the homeopathic medicinal product (month and year), a warning instructing patients to consult a physician if symptoms fail to disappear during use of the homeopathic medicinal product;
- a special warning, if necessary;
- dispensing of the homeopathic medicinal product;
- batch number, and
- number of the decision on the enrolment in the register of the homeopathic medicinal product.
4. What are the regulatory requirements for over-the-counter (non-prescription) medications?
Over the counter medications are regulated by Medicinal Products Act and its regulations. Requirements for development, manufacture, authorization and pricing are in general the same for all medicinal products.
Medicinal products are subject to medical prescription where they:
- are likely to present a danger either directly or indirectly, even when used correctly, if utilized without medical supervision;
- are frequently and to a very wide extent used incorrectly, and as a result are likely to present a direct or indirect danger to human health;
- contain substances or preparations thereof, the activity and/or adverse reactions of which require further investigation, or
- are normally prescribed by a doctor to be administered parenterally.
Medicinal products not covered by these criteria may be dispensed without medical prescription.
5. Are there any limitations on locations or channels through which OTC products may be sold?
Medicinal products not subject to medical prescription are dispensed in pharmacies and also in specialized retail sale outlets for medicinal products in line with the marketing authorisation granted by the Agency.
Private individual and business entitiy engaged in pharmacist activity in Croatia may over the Internet offer for distance selling, in line with a special regulaton, medicinal products which are not subject to medical prescription.
6. What health, advertising, and marketing claims may be made for OTC products?
In the advertising of a medicinal product that is dispensed without a prescription, the following message has to be contained within the advertisement or in the notification: “Prior to use, carefully read the instructions for use, and consult your doctor or pharmacist about the possible risks and adverse reactions”.
The warning has be prominent (e.g. in a noticeable colour or in a frame) and takes up at least one-tenth of the size of the advertisement, and has to be written in a font size that can be read without difficulty.
For television advertisements, the warning has to be shown independently (in its own shot) and has to be read in a clearly understandable voice.
For television and radio advertisements, advertisements serving as a reminder are implemented in such a way that in the promotional block, the entire advertisement of the medicinal product is played in its entirety, and following this in the same promotional form, the advertisement may follow as a reminder.
In internet advertising, the warning has to be an integral part of the main page of the advertisement, and not a link.
The advertisement of the medicinal product may not be misleading, and it has to be clearly visible that it is an advertisement. In printed articles and articles published on the internet which advertise the medicinal product, it is necessary to state: “Sponsored advertisement of a medicinal product” in a visible part of the article, with a font size equal to or larger than the font size in the remainder of the article.
The advertisement on the medicinal product for which advertising is permitted towards the population, contains at least the following information:
- name of the medicinal product, if the medicinal product contains only one active substance and the international name of the active substance;
- necessary notification for proper use, and
- informing patients to carefully read the package leaflet or the instructions on the external packaging or container of the medicinal product.
Advertising on a medicinal product that serves as a reminder and consists exclusively of the name of the medicinal product or joint name of multiple medicinal products, is exempted from the motion of the above-mentioned requirements from, and the requirement Ordinance on the Manner of Advertising Medicinal Products.
The following is not permitted in advertising a medicinal product towards the population:
- claims that the medicinal product has no adverse reactions, is not toxic or has no risk of addiction, or diminishing the significance and frequency of adverse reactions;
- giving the impression that the medicinal product guarantees success in the treatment of disease;
- suggesting that a specific medicinal product is undoubtedly better than other medicinal products;
- claims that the medicinal product may be taken when there are no signs of disease, i.e. that it improves health;
- claims that not taking the medicinal product may negatively impact health, except in the case refulated by Ordinance on the manner of advertising medicinal products;
- suggesting that the medicinal product is safe and efficient due to its natural origin;
- claim that the medicinal product represents a dietary, cosmetic or other mass use product;
- suggesting that by taking the medicinal product a person may avoid a physician’s exam, advise or surgical procedure, and giving diagnoses or offering advise on treatment via post or e-mail;
- suggesting that a prescribed medicinal product be replaced by another;
- advertisement directed exclusively or primarily towards children, showing children taking the medicinal product on their own, or that the medicinal product is within their reach without the presence of an adult;
- including the recommendation of healthcare professionals or scientists, or including in the advertisement persons whose popularity could stimulate the use of the medicinal product;
- listing the notice of the inclusion of the medicinal product on the list of medicinal products prescribed in Croatia at the expense of the mandatory healthcare insurance fund in the system of primary, secondary and tertiary healthcare, except in the cases from Article 7, paragraph 3 of this Ordinance;
- use of the medical history or simulation of diagnostic procedures that could lead to incorrect self-treatment or self-diagnosis;
- use of illustrative displays of changes to the human body caused by disease, injury or effect of a medicinal product on the human body or parts of the body in an inappropriate, disturbing or misleading manner, or
- referring to evidence of cures in an inappropriate, disturbing or misleading manner.
7. Can OTC products be marketed or advertised directly to the public?
Yes. Advertising towards the population is permitted exclusively for medicinal products that are dispensed without a prescription (over-the-counter), pursuant to the marketing authorisation for the medicinal product.
8. What is the mechanism by which a prescription-only product can be converted to an OTC product?
Mechanism by which a prescription-only product can be converted to an OTC product is regulated by Ordinance on Granting Marketing Authorisations for Medicinal Products and Medicinal Products Act.
The conditions, documentation and manner of approving changes to the manner of dispensing medicinal products is conducted pursuant to the valid guidelines of the European Commission, recommendations of the European Directorate for the Quality of Medicines (hereinafter: EDQM) and the provisions of this Ordinance on Granting Marketing Authorisations for Medicinal Products (Official Gazette No. 83/13).
Alongside the documentation on the medicinal product for which the authorization holder wants to change the manner of dispensing, the authorisation holder is obliged to submit:
- the proposal of the Summary of product characteristics, package leaflets and labelling of the medicinal product, including a mock-up of the external and internal packaging of the medicinal product;
- risk management plan that defines the possible risks stemming from the changes to the manner of dispensing the medicinal product, and the proposal for managing those risks, if necessary, and
- results of testing the comprehensibility and simplicity of the package leaflet.
The authorisation holder is obliged to submit the request for approval of the changes of the manner of dispensing the product.
Alongside the request for a change of the place of dispensing the medicinal product, the authorisation holder is obliged to submit the following documentation:
- expert report on the clinical documentation that should contain a critical review of the safety of the medicinal product, with regard to the dispensing of the medicinal product outside of pharmacies;
- data on the expert for the clinical documentation;
- proposal of the Summary of product characteristics, package leaflets, labelling of the medicinal product and mock-up of the external and internal packaging of the medicinal product;
- risk management plan that defines the possible risks stemming from changes to the place of dispensing the medicinal product, and proposals for managing those risks, if necessary, and
- results of testing the comprehensibility and simplicity of the package leaflets, if applicable.
The Agency website provides the conditions for approval of the place and/or manner of dispensing the medicinal product, taking into account the safety profile of the active substance, motion route of the medicinal product, pharmaceutical, size of packaging, maximum individual daily dose, indications or other conditions of use of the medicinal product.
For medicinal products meeting the prescribed conditions, the authorization holder is obliged to confirm that all the prescribed conditions have been met in full.
On its website, the Agency publishes the list of medicinal products having marketing authorisation in Croatia, with regard to the manner and place of dispensation.
By way of derogation, the Agency may, pursuant to new findings about the medicinal product, re-examine its prior decision on classification of the medicinal product, if it deems that it is necessary, for the purpose of protecting the health of the population, to alter the manner and/or place of dispensation of the medicinal product, and has to inform the marketing authorisation holder thereof. The marketing authorisation holder, pursuant to the Agency notification, is obliged within a deadline of 30 days from the date of delivery of the notification, to initiate the appropriate procedure for the authorisation of amendments to the manner and place of dispensation of the medicinal product, in accordance with the Medicinal Products Act and the ordinances adopted pursuant to the Act.
9. What are the requirements for the importation of either traditional medicines or OTC products?
Only medicinal products in respect of which a marketing authorization has been granted and medicinal products in respect of which an authorisation for parallel imports or parallel distribution has been granted may be distributed in Croatia.
Provisions of Medicinal Products Act relating import appropriately applies to the traditional herbal medicinal products as well as to OTC medicinal products.
Import of medicinal products is conducted by importers of medicinal products complying with the requirements of Good Manufacturing Practice in the extent that applies to them. For conducting the above-mentioned activity, a manufacturing authorization is required.
Importers importing medicinal products from third countries, and who do not have at their disposal premises and equipment for quality control of every batch of imported medicinal products, may for that purpose conclude a contract with a business entity or private individual possessing a manufacturing authorisation that covers quality control of medicinal products.
Batches of medicinal products on which quality control was conducted in an another Member State of the European Union or, are not be subject to additional quality control, but can also be released in Croatia on the basis of a certificate of quality control of a medicinal product in a Member State of the European Union signed by a responsible person for release of a medicinal product batch.
When a medicinal product is imported from a state which has concluded an agreement on mutual recognition in the field of medicinal products with the European Union, a medicinal product is placed on the market in Croatia on the basis of a certificate of quality control from the exporting country.
Business entity and private individual seated in Croatia conducting the activities of manufacture, import and supply of active substances are enroled in the register of manufacturers, importers, or wholesalers of active substances.
The certificate of the compliance with the Good Manufacturing Practice is issued by the Agency inspection, within 90 days from conducting supervision of the Good Manufacturing Practice at the request of the manufacturer or the importer.
The Minister of Health lays down in an ordinance the method of the issuing the certificate of compliance with the Good Manufacturing Practice.
Agency’s approval for entry or import is not required for:
- medicinal products authorised for wholesale distribution by the Agency or the European Commission;
- medicinal products authorised for parallel importation or parallel distribution;
- active substances and excipients, and
- intermediate products or medicinal products, where some production processes are carried out in Croatia.
The above-mentioned exemptions do not apply to the approval for entry or importation of:
- medicinal products made of human blood or plasma;
- immunological medicinal products, and
The Minister issues an ordinance establishing detailed conditions for granting the approval for entry or importation of medicinal products in these cases