1 This request for a preliminary ruling concerns the interpretation of Article 1(2)(b) of Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use (OJ 2001 L 311, p. 67), as amended by Directive 2010/84/EU of the European Parliament and of the Council of 15 December 2010 as regards pharmacovigilance (OJ 2010 L 348, p. 74) (‘Directive 2001/83’).
2 The request has been made in proceedings between M2Beauté Cosmetics GmbH and Bundesrepublik Deutschland (Federal Republic of Germany), represented by the Bundesinstitut für Arzneimittel und Medizinprodukte (Federal Institute for Drugs and Medical Devices, Germany) (‘BfArM’), concerning a decision by which the latter found that a product intended to promote eyelash growth, marketed as a cosmetic product by M2Beauté Cosmetics, had to be classified as a medicinal product rather than a cosmetic product.
3 Recitals 2 and 7 of Directive 2001/83 are worded as follows: ‘(2) The essential aim of any rules governing the production, distribution and use of medicinal products must be to safeguard public health. … (7) The concepts of harmfulness and therapeutic efficacy can only be examined in relation to each other and have only a relative significance depending on the progress of scientific knowledge and the use for which the medicinal product is intended. The particulars and documents which must accompany an application for marketing authorisation for a medicinal product demonstrate that potential risks are outweighed by the therapeutic efficacy of the product.’
4 Under Article 1(2) of that directive, contained in Title I thereof, entitled ‘Definitions’: ‘For the purposes of this Directive, the following terms shall bear the following meanings: Medicinal product: (a) Any substance or combination of substances presented as having properties for treating or preventing disease in human beings; or (b) Any substance or combination of substances which may be used in or administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis.’
5 Article 2 of that directive states: ‘1. This Directive shall apply to medicinal products for human use intended to be placed on the market in Member States and either prepared industrially or manufactured by a method involving an industrial process. 2. In cases of doubt, where, taking into account all its characteristics, a product may fall within the definition of a “medicinal product” and within the definition of a product covered by other Community legislation the provisions of this Directive shall apply. …’
6 Article 6(1) of that directive provides: ‘No medicinal product may be placed on the market of a Member State unless a marketing authorisation has been issued by the competent authorities of that Member State in accordance with this Directive or an authorisation has been granted in accordance with Regulation (EC) No 726/2004 [of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (OJ 2004 L 136, p. 1)], read in conjunction with Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use [and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004 (OJ 2006 L 378, p. 1)] and Regulation (EC) No 1394/2007 [of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004 (OJ 2007 L 324, p. 121)]. …’
7 Article 8(1) of Directive 2001/83 sets out: ‘In order to obtain an authorisation to place a medicinal product on the market regardless of the procedure established by [Council] Regulation (EEC) No 2309/93 [of 22 July 1993 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Products (OJ 1993 L 214, p. 1)], an application shall be made to the competent authority of the Member State concerned.’
8 Article 8(3)(i) and (ia) of that directive provides: ‘The application shall be accompanied by the following particulars and documents, submitted in accordance with Annex I: … (i) Results of: - pharmaceutical (physico-chemical, biological or microbiological) tests, - pre-clinical (toxicological and pharmacological) tests, - clinical trials. (ia) A summary of the applicant’s pharmacovigilance system which shall include the following elements: - proof that the applicant has at his disposal a qualified person responsible for pharmacovigilance, - the Member States in which the qualified person resides and carries out his/her tasks, - the contact details of the qualified person, - a statement signed by the applicant to the effect that the applicant has the necessary means to fulfil the tasks and responsibilities listed in Title IX, - a reference to the location where the pharmacovigilance system master file for the medicinal product is kept.’
9 Regulation No 726/2004 replaced Regulation No 2309/93. Under the second paragraph of Article 88 of Regulation No 726/2004, references to Regulation No 2309/93 are to be construed as references to Regulation No 726/2004.
10 Article 1 of Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products (OJ 2009 L 342, p. 59), entitled ‘Scope and objective’, is worded as follows: ‘This Regulation establishes rules to be complied with by any cosmetic product made available on the market, in order to ensure the functioning of the internal market and a high level of protection of human health.’
11 Article 2 of that regulation, entitled ‘Definitions’, sets out in paragraph 1(a) thereof: ‘“cosmetic product” means any substance or mixture intended to be placed in contact with the external parts of the human body (epidermis, hair system, nails, lips and external genital organs) or with the teeth and the mucous membranes of the oral cavity with a view exclusively or mainly to cleaning them, perfuming them, changing their appearance, protecting them, keeping them in good condition or correcting body odours.’
12 Article 13 of that regulation, entitled ‘Notification’, provides in paragraph 2 thereof: ‘When the cosmetic product is placed on the market, the responsible person shall notify to the [European] Commission the original labelling, and, where reasonably legible, a photograph of the corresponding packaging.’
13 Paragraph 2(1), (3) and (3a) of the Gesetz über den Verkehr mit Arzneimitteln (Arzneimittelgesetz - AMG) (Law on the Marketing of Medicinal Products) of 24 August 1976 (BGB1. 1976 I, p. 2445), in its version applicable to the dispute in the main proceedings (‘the AMG’), provides: ‘(1) Medicinal products are substances or preparations made from substances that: 1. are intended for use in or on the human or animal body and are intended for use as remedies with properties for the curing, alleviating or preventing of human or animal diseases or disease symptoms or 2. can be used in or on the human or animal body or can be administered to a human being or an animal, either: (a) to restore, correct or influence the physiological functions through a pharmacological, immunological or metabolic effect, or (b) to make a medical diagnosis. … (3) The term “medicinal product” does not apply to: … 2. cosmetic products within the meaning of Paragraph 2(5) of the Lebensmittel-, Bedarfsgegenstände- und Futtermittelgesetzbuch (Lebensmittel- und Futtermittelgesetzbuch - LFGB) (Code on Foodstuffs, Consumer Staples and Animal Feed) … . (3a) Medicinal products are also products which are or contain substances or preparations based on substances which, having regard to all their characteristics, are covered by a definition in paragraph 1 and are at the same time capable of falling within the definition of a product in accordance with paragraph 3.’
14 Paragraph 21(4) of the AMG states: ‘Furthermore, at the request of the competent authority of the Land, the competent higher federal authority decides on the obligation to obtain a marketing authorisation …’
15 Paragraph 2(5) of the Code on Foodstuffs, Consumer Staples and Animal Feed, in its version applicable to the dispute in the main proceedings, states: ‘Cosmetic products are substances or mixtures of substances which are intended exclusively or essentially for external use, on the human body or in its oral cavity, for cleaning, protecting, keeping in good condition, perfuming, changing appearance, or used for correcting body odours. Substances or mixtures of substances intended to modify the shape of the body are not cosmetic products.’
16 M2Beauté Cosmetics, a company established in Germany, developed a product called ‘M2 Eyelash activating serum’, which it markets as a cosmetic product. According to M2Beauté Cosmetics, the product concerned increases eyelash growth and density by up to 50%. It is packaged in an elongated bottle containing an integrated brush.
17 That product contains an active substance designating ‘methylamide-dihydro-noralfaprostal’ (‘MDN’), the concentration level of which varies, according to the statements of the German Government during the written part of the procedure, between 0.001% and 0.302%.
18 MDN is a new synthetic active substance belonging to the prostaglandin derivative group related to the human tissue hormone prostaglandin. It is largely identical in its molecular structure to bimatoprost (‘BMP’), which is authorised in Germany as a medicinal product and marketed under the name ‘Lumigan’ in eye drops for the treatment of glaucoma. In the United States, BMP has also been approved as a medicinal product for the treatment of eyelash hypotrichosis and is marketed under the name ‘Latisse’. Those two products contain BMP with a 0.03% concentration.
19 By decision of 29 April 2014, the BfArM held that the product concerned, namely ‘M2 Eyelash activating serum’, was not a cosmetic product but a ‘medicinal product by function’ within the meaning of Paragraph 2(1), point 2(a) of the AMG, which is intended to transpose Article 1(2)(b) of Directive 2001/83 into German law.
20 Notwithstanding the lack of any study of MDN’s chemical and biological properties, the BfArM took the view, in its decision, that the effects of that substance and those of BMP are comparable, since the molecular structures of those two substances are similar. Such an assumption is confirmed by the fact that M2Beauté Cosmetics found, in a series of tests which it carried out, increased eyelash growth when using the active substance at issue in the main proceedings. Consequently, MDN has a pharmacological effect by interacting with the prostamide receptor.
21 Furthermore, according to the BfArM, like BMP, the lengthening and thickening of eyelashes also correspond to a significant impact of MDN on physiological functions. Finally, the classification of the product concerned as being a ‘medicinal product by function’, within the meaning of Paragraph 2(1), point 2(a) of the AMG, also stems from the fact that it is impossible to rule out the existence of a risk to health if that product is used. By reason of a structural analogue, side effects similar to those of BMP are likely as regards MDN, namely hyperaemia, resulting in redness, conjunctivitis, itchy eyes or headaches.
22 Following administrative objection proceedings, M2Beauté Cosmetics brought an action before the referring court on 9 November 2017 for annulment of the BfArM’s decision.
23 In support of that action, M2Beauté Cosmetics claims that the pharmacological effect of the product concerned has not been proved. In addition, it takes the view that it follows from the case-law of the Court that the concept of a ‘medicinal product’, within the meaning of Directive 2001/83, excludes substances whose effects are limited to a mere modification of physiological functions, without being capable of having direct or indirect beneficial effects on human health, as required by Article 1(2)(b) of Directive 2001/83.
24 Thus, the referring court questions the extent of the power of the national authorities and courts to establish the pharmacological effects of a product and the risks associated with it, in the absence of sufficient scientific knowledge concerning the active substance applied with a specific dosage and use. It takes the view that the pharmacological effect of that product would be established only if the structural analogy, adopted by the BfArM, between the active substance used in the present case, MDN, and the structural analogue concerned, BMP, was sufficient.
25 In those circumstances, the Verwaltungsgericht Köln (Administrative Court, Cologne, Germany) decided to stay the proceedings and to refer the following questions to the Court of Justice for a preliminary ruling: ‘(1) Is a national authority, when classifying a cosmetic product as a “medicinal product by function”, within the meaning of Article 1(2)(b) of [Directive 2001/83] and, in so doing, examining all the characteristics of that product, entitled to base the necessary scientific assessment of the pharmacological properties of that product and the risks associated with it on a “structural analogy”, in a case where the active substance used has only recently been developed, is comparable in its structure to pharmacological active substances which are already known and studied, but no comprehensive pharmacological, toxicological or clinical studies of the new substance in relation to its effects and its dosage, which are necessary only if [Directive 2001/83] is applicable, have been submitted by the applicant? (2) Is Article 1(2)(b) of [Directive 2001/83] to be interpreted as meaning that a product which is placed on the market as a cosmetic and which significantly modifies physiological functions by producing a pharmacological effect is to be regarded as a medicinal product by function only in the case where it has a specific positive health-promoting effect? Is it sufficient in this regard even that the product has on a person’s appearance a predominantly positive effect which, by increasing self-esteem or well-being, is of indirect benefit to health? (3) Or is that product also a medicinal product by function in the case where its positive effect is confined to an improvement in a person’s appearance, without being of direct or indirect benefit to health, but where it does not have properties that are exclusively harmful to health and is not therefore comparable to a narcotic?’
26 By its first question, the referring court asks, in essence, whether Article 1(2)(b) of Directive 2001/83 must be interpreted as meaning that a national authority may, for the purpose of classifying a product as a ‘medicinal product’, within the meaning of that provision, establish the pharmacological properties of that product by relying on scientific knowledge relating to a structural analogue of that substance, where no scientific study of the substance in question is available.
27 In the first place, it should be noted that Article 1(2)(a) and (b) of Directive 2001/83 provides two definitions of the concept of a ‘medicinal product’. A product therefore constitutes a medicinal product, within the meaning of that directive if it satisfies the definition of a ‘medicinal product by presentation’ or the definition of a ‘medicinal product by function’ (see, to that effect, judgment of 3 October 2013, Laboratoires Lyocentre, C‑109/12, EU:C:2013:626, paragraph 36 and the case-law cited).
28 As regards the second definition of the concept of a ‘medicinal product’, in Article 1(2)(b) of Directive 2001/83, ‘any substance or combination of substances which may be used in or administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis’ is regarded as a ‘medicinal product by function’.
29 According to settled case-law, contrary to the definition of ‘medicinal product by presentation’, the broad interpretation of which is intended to protect consumers from products which do not have the effectiveness which they are entitled to expect, the definition of ‘medicinal product by function’ is designed to cover products the pharmacological properties of which have been scientifically observed (see, to that effect, judgments of 15 January 2009, Hecht-Pharma, C‑140/07, EU:C:2009:5, paragraph 25 and the case-law cited, and of 6 September 2012, Chemische Fabrik Kreussler, C‑308/11, EU:C:2012:548, paragraph 30).
30 In particular, for the purposes of classifying a product as a ‘medicinal product by virtue of its function’, for the purposes of Directive 2001/83, the national authorities, acting under the supervision of the courts, must decide on a case-by-case basis, taking account of all the characteristics of the product, in particular its composition, its pharmacological, immunological or metabolic properties, to the extent to which they can be established in the present state of scientific knowledge, the manner in which it is used, the extent of its distribution, its familiarity to consumers and the risks which its use may entail (judgment of 3 October 2013, Laboratoires Lyocentre, C‑109/12, EU:C:2013:626, paragraph 42).
31 In the second place, it should be noted that the first question relates more specifically to the assessment of the pharmacological properties of the substance contained in the product concerned, which must be ‘scientifically established’ or ‘established in the current state of scientific knowledge’ for the purposes of the classification of that product as a ‘medicinal product by function’, where such an assessment is not based on studies relating to the substance concerned in the strict sense, but results solely from scientifically based assessments relating to a structural analogue of that substance.
32 In that regard, it must be borne in mind that the condition that the pharmacological properties of the substance concerned must be ‘scientifically established’ or established ‘in the current state of scientific knowledge’ refers primarily to studies on the substance concerned. However, that condition cannot preclude account being taken of other scientific knowledge which makes it possible to establish those pharmacological properties, even in the absence of studies specifically relating to that substance.
33 Consequently, if, for a substance which has not been the subject of any specific study, the current state of scientific knowledge relating to structural analogues leads to the conclusion that that substance has effects comparable to those of another existing substance, and therefore to assessing the pharmacological effect of that substance with a given concentration, which will be for the referring court to ascertain, that condition relating to the existence of a ‘scientific finding’ must be regarded as satisfied.
34 Moreover, such an interpretation is in keeping with the mechanism the EU legislature established by adopting Directive 2001/83. That directive in fact requires every person wishing to market a medicinal product to submit an application for marketing authorisation for that medicinal product, in accordance with Article 6(1) of that directive. It also requires that, for the purpose of granting that authorisation, the results of pharmaceutical, pre-clinical tests and clinical trials be submitted, as well as a description of the pharmacovigilance system, in accordance with Article 8(3)(i) and (ia) of that directive.
35 Therefore, the studies relating to a medicinal product are intended to serve as a basis for granting a marketing authorisation which is based on an examination in relation to each other of the harmfulness and therapeutic efficacy, as confirmed by recital 7 of Directive 2001/83. Accordingly, the conduct of pharmaceutical, pre-clinical tests and clinical trials required prior to granting such a marketing authorisation makes it possible for the competent authorities to weigh up the risks associated with a particular substance and its capacity to treat a given pathological condition, depending, in particular, on the progress of scientific knowledge.
36 That said, it cannot be accepted that the conditions laid down in Directive 2001/83 and, in particular, the obligation to provide studies relating to the properties of a medicinal product prior to any placing on the market are circumvented, for example by presenting that product as being a ‘cosmetic product’, within the meaning of Article 2(1)(a) of Regulation No 1223/2009. This would be contrary both to the objective pursued by that directive and the wording of Article 2(2) thereof, according to which, in cases of doubt, where, taking into account all its characteristics, a product may fall within the definition of a ‘medicinal product’ and within the definition of a product covered by other EU legislation the provisions of that directive apply.
37 In the case of a structural analogue to an existing substance, such a risk of circumvention would not arise if the degree of analogy were such that, on the basis of an objective and scientifically substantiated analysis, it could be presumed that a substance present in a product with a given concentration has the same properties as an existing substance for which the required studies are available. In such a case, a national authority may therefore rely on the existence of the structural analogue concerned in order to establish the pharmacological properties of the product in question, taking into account the manner in which it is used, the extent of its distribution, its familiarity to consumers and the risks which its use may entail for the purpose of classifying that product as ‘medicinal product by function’, referred to in Article 1(2)(b) of Directive 2001/83.
38 In the light of the foregoing considerations, the answer to the first question is that Article 1(2)(b) of Directive 2001/83 must be interpreted as meaning that a national authority may, for the purpose of classifying a product as a ‘medicinal product’, within the meaning of that provision, establish the pharmacological properties of that product by relying on scientific knowledge relating to a structural analogue of that substance, where no scientific study of the substance of which that product consists is available, if the degree of analogy is such that it may be assumed on the basis of an objective scientific assessment that a substance present in a product with a given concentration has the same properties as an existing substance for which the required studies are available.
39 By its second and third questions, which it is appropriate to examine together, the referring court asks, in essence, whether Article 1(2)(b) of Directive 2001/83 must be interpreted as meaning that a product which modifies physiological functions, but which has no beneficial effect on health may be classified as a ‘medicinal product’, within the meaning of that provision, where it improves appearance without having harmful properties.
40 In the first place, it should be observed that, although, in accordance with its usual meaning in everyday language, the term ‘modify’ does not prejudge the beneficial or harmful nature of the effects, it is nevertheless settled case-law that, for the purpose of interpreting a provision of EU law, it is necessary to consider not only its wording but also its context and the objectives of the legislation of which it forms part (judgment of 26 April 2022, Landespolizeidirektion Steiermark (Maximum duration of internal border control), C‑368/20 and C‑369/20, EU:C:2022:298, paragraph 56).
41 In the present case, Article 1(2)(b) of Directive 2001/83 must be interpreted in the light of the objective pursued by that directive, namely to ensure a high level of protection of human health.
42 In that regard, the expression ‘modify the physiological functions’, within the meaning of Article 1(2)(b) of Directive 2001/83, must be interpreted as referring to substances which are capable of having a beneficial effect on the functioning of the human organism and, as a consequence, on human health (see, to that effect, judgment of 10 July 2014, D. and G., C‑358/13 and C‑181/14, EU:C:2014:2060, paragraphs 30 to 33 and 37).
43 A ‘medicinal product by function’ referred to in Article 1(2)(b) of Directive 2001/83, must have the potential capacity of having immediate or long-term beneficial effects for human health (see, to that effect, judgment of 3 October 2013, Laboratoires Lyocentre, C‑109/12, EU:C:2013:626, paragraph 43 and the case-law cited).
44 In the second place, as regards the characterisation of an effect likely to be regarded as beneficial to health, it should be noted that the assessment which the national authorities are required to carry out for the purpose of classifying a product as a ‘medicinal product by function’, referred to in Article 1(2)(b) of Directive 2001/83, is a case-by-case assessment, as recalled in paragraph 30 above.
45 In order to do so, the national authorities must, as also stated in paragraph 30 above, take account of all the characteristics of the product concerned, including, in particular, its composition, its pharmacological, immunological or metabolic properties, the manner in which it is used, the extent of its distribution, its familiarity to consumers and the risks which its use may entail.
46 The health-promoting effects of a product cannot therefore be assessed in the abstract, without taking into account the specific use to which that product will be put. The fact that a product is likely to improve appearance without having harmful properties or that it may improve appearance and consequently lead to an increase in self-esteem or well-being is not sufficient, in itself, to ensure that health benefits are ‘scientifically established’.
47 Moreover, according to settled case-law, beneficial effects which the substance concerned is capable of having on the functioning of the human organism may be immediate or over a period of time, even in the absence of disease (see, to that effect, judgment of 10 July 2014, D. and G., C‑358/13 and C‑181/14, EU:C:2014:2060, paragraph 36).
48 However, while it is possible that a product, in the absence of disease, satisfies the definition of ‘medicinal product by function’ referred to in Article 1(2)(b) of Directive 2001/83, the fact that that product may be prescribed for therapeutic purposes is a decisive factor with a view to its classification as ‘medicinal product by function’.
49 Therefore, if it is established on the basis of scientific studies that a product is regarded as suitable for use in the treatment of a recognised pathological condition, which will be is for the referring court to ascertain, the finding of beneficial effects on health must follow.
50 Conversely, in the absence of any, even potential, use of the product concerned for the treatment of a recognised pathological condition, the condition relating to the existence of beneficial effects on health will not be satisfied.
51 In that regard, it must be noted that the mere fact of improving appearance without having harmful properties cannot suffice for a finding that a product may give rise to beneficial effects on health and may therefore meet the definition of medicinal product by function, referred to in Article 1(2)(b) of Directive 2001/83. In that connection, it should be borne in mind that the capacity to restore, correct or modify physiological functions should not lead to the classification as medicinal products by function of products which, while having an effect on the human body, do not significantly affect the metabolism and thus do not strictly modify the way in which it functions (judgment of 30 April 2009, BIOS Naturprodukte, C‑27/08, EU:C:2009:278, paragraph 21).
52 Consequently, classification as a medicinal product by function, referred to in that provision, requires that it be possible to establish that the product concerned is potentially capable of inducing a specific benefit to health. If that is not the case, that product cannot be regarded as having such a classification. In addition, it should be noted that, although that benefit may result from an improvement in appearance, taking into account the increase in self-esteem or well-being which that improvement gives rise to, such an assessment cannot be carried out by a subjective assessment, but must be based on a scientific finding. Such a condition is satisfied where the product is regarded as capable of being used as a treatment for a recognised pathological condition, which will be for the national court to ascertain.
53 In the light of the foregoing considerations, the answer to the second and third questions is that Article 1(2)(b) of Directive 2001/83 must be interpreted as meaning that a product which modifies physiological functions may be classified as a ‘medicinal product’, within the meaning of that provision, only if it has specific health-promoting effects. In that regard, an improvement in appearance, which gives rise to an indirect benefit through an increase in self-esteem or well-being, is sufficient where it permits the treatment of a recognised pathological condition. By contrast, a product which improves appearance without having harmful properties and which has no beneficial effects on health cannot be classified as a ‘medicinal product’, within the meaning of that provision.
54 Since these proceedings are, for the parties to the main proceedings, a step in the action pending before the national court, the decision on costs is a matter for that court. Costs incurred in submitting observations to the Court, other than the costs of those parties, are not recoverable.