Traditional Medicines and OTC Products
The ins and outs of traditional medicines and OTC products in Greek pharma. Prepared in association with Calavros Law Firm, a leading global law firm, this is an extract from The Pharma Legal Handbook: Greece, available to purchase here for USD 99.
1. What are the regulatory requirements for traditional, herbal, complementary, or alternative medicines and devices?
Legal provisions pertaining to the regulatory requirements of the various types of medicinal products and medical devices may be found in various Interministerial Decisions and laws. The medicinal products which are placed on the Greek market are mainly regulated by Interministerial Decision D.YG3α/G.P. 32221/Government Gazette B 1049/2013 (read together with Legislative Decree 96/1973 as regards traditional medicines) and by Interministerial Decision G5(a)/53625/Government Gazette B 3328/2017 relating to food supplements. Moreover, the regulatory requirements of medicinal devices are stipulated under Interministerial Decision DY8d/G.P. 130648/Government Gazette B’ 2198/2009, Interministerial Decision DY8d/130644/Government Gazette B’ 2197/2009 and Interministerial Decision DY8d/G.P. 3607/Government Gazette B’ 1060/2001.
The definition of traditional medicines is provided by article 1(1) of Legislative Decree 96/1973 in conjunction with article 2 of Interministerial Decision D.YG3α/G.P. 32221/Government Gazette B 1049/2013. A (traditional) medicinal product is any substance or combination of substances presented for treating or preventing disease in human beings. Moreover, any substance or combination of substances which may be administered to human beings with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions in human beings through the exercise of pharmacological, immunological or metabolic action is likewise considered a medicinal product. The regulatory requirements of traditional medicines are stipulated in Interministerial Decision D.YG3α/G.P. 32221/Government Gazette B 1049/2013 read together with Legislative Decree 96/1973 (see the section Regulatory, Pricing and Reimbursement).
Pursuant to article 2(33) of the above Interministerial Decision, as herbal medicinal product is defined any medicinal product, exclusively containing as active ingredients one or more herbal substances or one or more herbal preparations, or one or more such herbal substances in combination with one or more such herbal preparations. The specific definition is in line with Directive 2004/24/EC amending, as regards traditional herbal medicinal products, Directive 2001/83/EC on the Community code relating to medicinal products for human use.
A simplified registration procedure (traditional-use registration) is established for herbal medicinal products under Chapter 2a of the same Interministerial Decision. More specifically, pursuant to article 21 a simplified registration procedure is established under articles 22-28 for herbal medicinal products which fulfil all of the following criteria:
- they have indications exclusively appropriate to traditional herbal medicinal products which, by virtue of their composition and purpose, are intended and designed for use without the supervision of a medical practitioner for diagnostic purposes or for prescription or monitoring of treatment;
- They may exclusively be administered at a specified strength and posology;
- They constitute either an oral, external and/or inhalation preparation;
- The period of traditional use as laid down in Article 23(1) has elapsed;
- The data on the traditional use of the medicinal product is sufficient; in particular the product has proven not to be harmful in the specified conditions of use and the pharmacological effects or efficacy of the medicinal product are plausible on the basis of long-standing use and experience (of at least thirty years, a minimum of fifteen of which within the EU).
It is worth noting that according to article 22 of the same Interministerial Decision an applicant and registration holder must be established in the Community and submit an application to E.O.F.
As a general remark “alternative” medicines are not recognized –and therefore authorized as such- neither by European nor by Greek legislation. The only type of alternative medicines recognized are homeopathic medicines.
Pursuant to article 2(6) of the above Interministerial Decision a homeopathic medicine is any medicinal product prepared from products, substances or compositions called homeopathic stocks in accordance with a homeopathic manufacturing procedure described by the European Pharmacopoeia or, in absence thereof, by the pharmacopoeias currently used officially in the Member States. A homeopathic medicinal product may also contain a number of principles.
A special, simplified registration procedure is laid down in article 18 of Chapter 2 for the homeopathic medicines that restrictively satisfy the following conditions:
- they are administered orally or externally,
- no specific therapeutic indication appears on the labelling of the medicinal product or in any information relating thereto,
- there is a sufficient degree of dilution to guarantee the safety of the medicinal product; in particular, the medicinal product may not contain either more than one part per 10 000 of the mother tincture or more than 1/100th of the smallest dose used in allopathy with regard to active substances whose presence in an allopathic medicinal product results in the obligation to submit a doctor’s prescription.
If the above conditions are not met, the authorization process followed is the same as for traditional medicines. In any case, the relevant application must be submitted with E.O.F.
The only complementary products recognized at European and national legislative level are food supplements which are regulated by Interministerial Decision G5(a)/53625/Government Gazette B 3328/2017 in line with Direction 2002/46/EC on the approximation of the laws of the Member States relating to food supplements. Pursuant to article 2 of said Interministerial Decision, food supplements’ foodstuffs fall within the competence of EOF. Their purpose must be to supplement the normal diet and must constitute concentrated sources of nutrients or other substances with a nutritional or physiological effect, alone or in combination, marketed in dose form – namely forms such as capsules, pastilles, tablets, pills and other similar forms, sachets of powder, ampoules of liquids, drop dispensing bottles, and other similar forms of liquids and powders, designed to be taken in measured small unit quantities;
The manufacturer or the person marketing a food supplement must notify EOF of their placement on the market. Moreover, in accordance with article 4 of said Interministerial Decision, only vitamins and minerals listed in Annex I, in the forms listed in Annex II, may be used for the manufacture of food supplements and the manufacturer must obtain the relevant authorization by E.O.F.
In case a food supplement already circulates within EU and on the condition that it includes exclusively the vitamins and minerals listed in Annex I, the relevant notification to EOF shall be accompanied by an application, a sample of the label and the relevant fee, pursuant to article 10(1) of said Interministerial Decision.
According to article 1 of Interministerial Decision DY8d/G.P. 130648/Government Gazette B’ 2198/2009 as medical device is defined any instrument, apparatus, appliance, material or other article, whether used alone or in combination, including the software necessary for its proper application intended by the manufacturer to be used for human beings for the purpose of:
- Diagnosis, prevention, monitoring, treatment or alleviation of disease,
- Diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap,
- Investigation, replacement or modification of the anatomy or of a physiological process,
- Control of conception, and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means.
Medical devices must meet the essential requirements set out in Annex I of said Interministerial Decision which apply to them (as per article 3 of said Interministerial Decision). Devices, other than devices which are custom-made or intended for clinical investigations, considered to meet the essential requirements must bear the CE marking of conformity when they are placed on the market. The CE marking of conformity, must feature in a visible, legible and indelible form on the device or its sterile pack, where practicable and appropriate, and on the instructions for use. Where applicable, the CE marking must also feature on the sales packaging (article 17 of said Interministerial Decision).
Apart from the general Interministerial Decision on medical devices, several other Interministerial and Ministerial Decisions in force govern specific types of Medical Devices, such as, indicatively, Interministerial Decision DY8d/130644/Government Gazette B’ 2197/2009 issued in application of Directive 90/385/EEC on the approximation of the laws of the Member States relating to active implantable medical devices and Interministerial Decision DY8d/G.P. 3607/Government Gazette B’ 1060/2001 issued in application of Directive 98/79/EC on in vitro diagnostic medical devices. It should be noted that under European and Greek legislation the use of alternative medical devices is not authorized.
2. Can these traditional, herbal, complementary, or alternative products be advertised directly to the public?
The advertising of traditional, herbal and homeopathic products directly to the public is subject to multiple restrictions and regulations mainly stipulated under Interministerial Decision D.YG3α/G.P. 32221/Government Gazette B 1049/2013 (articles 118-132) jointly with legislative Decree 96/1973.
As a general rule, EOF prohibits any advertising of medicinal products which have not been granted a marketing authorization. The specific rule does not apply to homeopathic products∙ this derogation is provided for in article 132 of said Interministerial Decision. However, only the information specified in Article 94(1) may be used in the advertising of such medicinal products.
Moreover, in accordance with article 120 of said Interministerial Decision, the only medicinal products that are allowed to be advertised to the general public are those which, by virtue of their composition and purpose, are intended and designed for use without the intervention of a medical practitioner for diagnostic purposes or for the prescription or monitoring of treatment, upon advice by a pharmacist, if necessary. Pursuant to article 119 of said Decision, it is strictly prohibited to advertise medicinal products which: (a) are available on medical prescription only, (b) contain psychotropic or narcotic substances, such as those governed by the United Nations Conventions of 1961 and 1971, (c) are reimbursed by Social Security Institutions.
As regards complementary products, namely food supplements, Interministerial Decision G5(a)/53625/Government Gazette B 3328/2017 in line with Direction 2002/46/EC stipulates under articles 6-7 the two main rules to be followed:
- advertising must not attribute to food supplements the property of preventing, treating or curing a human disease, or refer to such properties
- advertising shall not include any mention stating or implying that a balanced and varied diet cannot provide appropriate quantities of nutrients in general.
Finally, it should be noted that the Hellenic Association of Pharmaceutical Companies (SFEE) Code of Ethics, provides specific guidelines on the advertising of medicinal products to the public. Therefore pharmaceutical companies active in Greece must be vigilant as regards compliance with said rules.
3. What health, advertising and marketing claims may be made for traditional, herbal, complementary, or alternative products?
Traditional, Herbal and Homeopathic Products
In general, the infringement of the regulatory framework on marketing and advertising of traditional, herbal and homeopathic products may under certain conditions establish either civil, criminal, administrative and / or disciplinary liability as examined in Chapter 5.
It should be noted that as regards advertising in particular, pursuant to article 121 of Interministerial Decision D.YG3α/G.P. 32221/Government Gazette B 1049/2013, attention must be paid so that all advertising to the general public of a medicinal product shall:
a. Be set out in such a way that it is clear that the message is an advertisement and that the product is clearly identified as a medicinal product;
b. Include the following minimum information:
- The name of the medicinal product, as well as the common name if the medicinal product contains only one active substance,
- The information necessary for correct use of the medicinal product,
- An express, legible invitation to read carefully the instructions on the package leaflet or on the outer packaging, as the case may be.
In addition, according to article 119(3) of said Interministerial Decision, the advertising of a medicinal product shall encourage the rational use of the medicinal product, by presenting it objectively and without exaggerating its properties and shall not be misleading.
The non-conformity with the above rules is also subject to the sanctions examined under Chapter 5, given that the sanctions for breach of the provisions of Interministerial Decision D.YG3α/G.P. 32221/Government Gazette B 1049/2013 are uniform.
In the event of infringement of the relevant regulatory provisions Interministerial Decision G5(a)/53625/Government Gazette B 3328/2017 on food supplements the sanctions stipulated under article 19 of Legislative Decree 96/1973 may be applicable, which provide, in principle, for the imposition of administrative fines. The civil, criminal, administrative and disciplinary liability of the persons in fault may also be respectively established on the grounds of claims brought by damaged persons, especially by consumers.
4. What are the regulatory requirements for over-the-counter (non- prescription) medications?
In general, over-the-counter medicines (hereinafter referred to as OTC medicines) are medicaments which, due to their composition and purpose, are intended and designed to be used without the intervention of a doctor for diagnosis or treatment, or in case of need, upon advice by a pharmacist.
According to article 97 of Interministerial Decision D.YG3α/G.P. 32221/Government Gazette B’ 1049/2013 , as medicinal products not subject to prescription are defined those which do not meet the criteria listed in Article 96. One must therefore examine which products are subject to medical proscription in order to be able to define the non-prescription medicines. Pursuant to article 96 of said Decision, medicinal products shall be 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, or 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, or
- 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.
Furthermore, the specific article provides for further classification to subcategories of medicines subject to special medical prescription and to restricted medical prescription. The relevant classification of a medicinal product is always and exclusively conducted by EOF during the marketing authorization process. It should be noted that EOF draws up a list of prescription-only medicines which is published on its website. The list is updated annually.
In view of the above, the regulatory requirements for non-prescription medicines follow in principle the regulatory requirements examined under Chapter 1. The differentiations regarding the sale and the advertising of OTC medicines are examined below and the relevant issues on pricing under question 12 of Regulatory, Pricing and Reimbursement.
5. Are there any limitations on locations or channels through which OTC products may be sold?
As regards the dispensation of OTC medicinal products, a distinction must be made between the general category of OTC medicinal products and ITS subcategory of General Dispensation Medicinal Products (Greek Acronym GEDIFA).
OTC products are exclusively dispensed through pharmacies, pursuant to article 4(1) of Law 1963/1991. The retail sale of medicinal products by pharmacies is also governed by Legislative Decree 312/1992 which regulates the organization and constitution of pharmacies at national level.
Medicinal Products (GEDIFA) are products already falling within the definition and classified as OTC products, which meet cumulatively the criteria set out in article 1(a) of Ministerial Decision G5(a) 51194/ Government Gazette B’ 2219/2016 in line with article 6 of Law 4389/2016. In general, GEDIFA products are medicines taken in response to obvious symptoms e.g. headache, nausea and the interactions of which with other frequently administered therapies are minimal.
Apart from their dispensation through legally operating pharmacies, OTC medicines may also be sold, in accordance with article 5 of said Decision, through retail shops of public health interest that have been authorized to operate as supermarkets or grocery stores.
6. What health, advertising, and marketing claims may be made for OTC products?
Greek legislation, in line with European legislation, does not establish any special health, advertising or marketing claims for OTC products. Such claims are uniform for all medicinal products, as specified under question 46 of this Chapter.
7. Can OTC products be marketed or advertised directly to the public?
In line with Interministerial Decision D.YG3α/G.P. 32221/Government Gazette B’ 1049/2013 only non-prescription (OTC) products (including herbal and homeopathic) may be advertised directly to the public, subject to the general restrictions already outlined above. The direct advertising of OTC products is jointly regulated by Ministerial Decision Y6a/2261/Government Gazette B’ 284/2002 on the advertising of medicinal products that may be administered without prescription which stipulates further specifications to be followed depending on the media used.
The same rules and processes as for the prescription-only medicinal products apply to the marketing of OTC products.
8. What is the mechanism by which a prescription-only product can be converted to an OTC product?
Whenever new data is brought to the attention of EOF, the latter is able to reevaluate and amend the classification of a medicine, in application of the criteria set out above under question 48.
9. What are the requirements for the importation of either traditional medicines or OTC products?
Interministerial Decision D.YG3α/G.P. 32221/Government Gazette B’ 1049/2013 also regulates the importation of medicinal products (in general) under its Title IV. The importation of a medicinal product from third (non EU) countries is subject to the granting of a manufacture authorization by EOF, according to the relevant provisions applicable.
In line with Directive 2011/62/EU on the prevention of entry into the legal supply chain of falsified medicinal products, according to said Decision EOF is entitled to take appropriate measures to ensure that the import and distribution in Greece of active substances, including active substances that are intended for export, comply with good manufacturing practices and good distribution practices for active substances.
According to article 74 (1) of said Decision, importers, manufacturers and distributors of active substances who are established in the Union shall register their activity with EOF.
The registration form shall include, at least, the following information:
- name or corporate name, permanent address and type of exercised activity;
- the active substances which are to be imported, manufactured or distributed and the type of manufacture and control;
- name and address of the active substance’s manufacturer and his/her GMP certificate if available
- particulars regarding the premises and the technical equipment for their activity.
- the countries where the active substance is distributed.
The persons referred to in paragraph 1 shall submit the registration form beforeEOF at least 60 days prior to the intended commencement of their activity.
Furthermore, pursuant to article 65(2) of said Decision, active substances shall only be imported if the following conditions are fulfilled:
- the active substances have been manufactured in accordance following good manufacturing practice standards at least equivalent to those laid down by the Union pursuant to the third paragraph of Article 66; and
- the active substances are accompanied by a written confirmation by the competent authority of the exporting third country of the following:
- the standards of good manufacturing practice applicable to the plant manufacturing the exported active substance are at least equivalent to those laid down by the Union pursuant to the third paragraph of Article 66;
- the manufacturing plant concerned is subject to regular, strict and transparent controls and to the effective enforcement of good manufacturing practice, including repeated and unannounced inspections, so as to ensure a protection of public health at least equivalent to that in the Union; and
- in the event of findings relating to non-compliance, information on such findings is supplied by the exporting third country to the Union without any delay.
The requirement set out in point (b) of paragraph 2 of this Article shall not apply if the exporting country is included in the Commission’s Third Countries Assessment List.