1.

Beauty is in the eye of the beholder. In this case, literally.

2.

The applicant in the main proceedings has developed and marketed the product ‘M2 Eyelash Activating Serum’ as a cosmetic product. According to the producer’s advertising: ‘The revolutionary [serum] makes your eyelashes longer and thicker, it achieves eyelash growth of almost 50%!’ The serum is a gel-like liquid contained in an elongated bottle with an integrated brush resembling an eyeliner container. It is to be applied once a day to the base of the upper eyelashes.

3.

However, aside from providing its customers with dense and long eyelashes, the producer of the serum is presently caught up in a dense and intricate scientific and legal web. That is why, before embarking upon the analysis of the questions referred by the national court, a more detailed presentation of the relevant facts is in order.

4.

The story begins with the treatment of glaucoma (an abnormally high intraocular pressure). Medicinal products developed for its treatment, when applied directly to the eye in the form of eye drops, have a well-established side effect of enhancing eyelash growth. ( 2 ) Glaucoma medicine resulted from pharmaceutical research that has led to the development of synthetic prostaglandins, which are structurally related to human prostaglandins. The prostaglandin analogue ‘bimatoprost’ (BMP) has been authorised in Germany as a medicinal product and is used as an active substance in eye drops for the treatment of glaucoma.

5.

The side effect of eyelash growth was subsequently noted and exploited outside the glaucoma treatment world. For example, in the United States, BMP and other analogues have been used in the production of medicinal products for the treatment of hypotrichosis of the eyelashes ( 3 ) and as cosmetics. ( 4 ) When used exclusively for eyelash growth, the active substance is not applied in the form of eye drops, but is rather applied to the skin of the upper eyelid margin at the base of the eyelashes. Such a method uses approximately 5% of the dose of the active substance used in eye drops for the treatment of glaucoma, and does not exert any influence on intraocular pressure. ( 5 )

6.

The ‘M2 Eyelash Activating Serum’ consists of, inter alia, an active substance ‘methylamide-dihydro-noralfaprostal’ (MDN). That substance is a structural analogue to BMP. ( 6 ) According to the information provided by the applicant in the main proceedings, there are at least 20 other products sold as cosmetic products throughout the European Union using MDN or other structural analogues as their active substance.

7.

By decision of 29 April 2014, the Bundesinstitut für Arzneimittel und Medizinprodukte (Federal Institute for Drugs and Medical Devices, Germany) (‘the BfArM’), acting on behalf of the respondent in the main proceedings, the Federal Republic of Germany, decided that that product was not a cosmetic but a medicinal product requiring a marketing authorisation.

8.

Following administrative objection proceedings in which the applicant in the main proceedings was unsuccessful, on 9 November 2017, it brought an action before the referring court seeking the annulment of that decision.

9.

In light of this background, the Verwaltungsgericht Köln (Administrative Court, Cologne, Germany) has submitted the following questions to the Court of Justice for a preliminary ruling:

10.

Written observations were submitted by the parties in the main proceedings, the Governments of Estonia and Greece, as well as the European Commission.

11.

The purpose of the Medicinal Products Directive ( 7 ) is set out in its recitals:

12.

In respect of risks and benefits to health in relation to medicinal products, the recitals state further:

13.

Article 1(2) of the Medicinal Products Directive provides two definitions of a medicinal product:

‘Medicinal product:

14.

Article 2(2) of the Medicinal Products Directive determines the scope of its application in situations of possible overlaps with other legislation:

‘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.’

15.

The manner in which medicinal products may be marketed under the Medicinal Products Directive is set out in Article 6(1):

‘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, ( 8 ) 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 ( 9 ) and Regulation (EC) No 1394/2007.’ ( 10 )

16.

Article 1 of the Cosmetics Regulation ( 11 ) sets out its objectives and scope 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.’

17.

What constitutes a cosmetic product? Article 2(1)(a) of the Cosmetics Regulation tells us that this is ‘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’.

18.

In order to ensure a high level of protection of human health, the Cosmetics Regulation provides that a cosmetic product shall be safe for human health (Article 3) and that this obligation rests on the person responsible for the product (Article 5).

19.

Furthermore, the responsible person must ensure the safety for human health by carrying out a safety assessment (Article 10) and notifying it to the Commission (Article 13). In addition, the safety of cosmetic products for human health may also be checked by the competent authority (Article 22).

20.

In the event that a cosmetic product has serious undesirable effects, the responsible person is to communicate that information without delay to the competent authority (Article 23). When a cosmetic product contains substances for which serious doubts arise as regards their safety, the competent authority may by reasoned request require the responsible person to submit a list of all the cosmetic products that contain such a substance (Article 24).

21.

In the event that the responsible person fails to comply with any of those obligations, the competent authority shall require the responsible person to take all appropriate measures, including the withdrawal from the market of the cosmetic product in question (Article 25(1)).

22.

Finally, when a cosmetic product raises serious risks for human health, the competent authority may also take all appropriate provisional measures to ensure that the product in question is withdrawn, recalled, or its availability is otherwise restricted (Article 27).

23.

The referring court’s questions invite the Court to provide clarity on the status of a product that at the moment finds itself on the thin line between a cosmetic and a medicinal product. In providing my answers, I will first explain under which conditions the relevant national authority, in carrying out its assessment, may use scientific evidence concerning structural analogues of active substances used in the product concerned (A).

24.

Next, in jointly answering the second and the third questions of the referring court (B), I will first present my reasons for concluding that the product in question does not fall within the scope of a medicinal product by function due to the lack of appreciable beneficial effects to health. In line with this conclusion, I will also explain why any possible harmful effects of the product in question should be dealt with under the system of the Cosmetics Regulation. Nevertheless, should the Court find that the Medicinal Products Directive applies, I will finally reflect upon the role of possible harmful effects of the product in question.

25.

By its first question, the referring court is asking whether the relevant authority, in determining whether a product using a new substance can be characterised as a medicinal product, can use scientific knowledge not concerning the active substance of the product itself, but its structural analogue.

26.

Since the Court’s judgment in van Bennekom, ( 12 ) we know that there is no general formula applying across the board in the determination of whether a certain product is medicinal under the Medicinal Products Directive. Rather, the national authority must always carry out a product-specific assessment based on the ‘present state of scientific knowledge’. The concept features consistently in decisions of the Court concerning the classification of a certain product as a medicinal product. ( 13 )

27.

In Delattre, ( 14 ) the Court specified that Member States must take account of international scientific research as well as the work of specialised EU committees, although no legislation expressly requires that this work be consulted before taking a decision.

28.

A further help in discerning the appropriate scientific standard may be drawn from the context of Article 116 of the Medicinal Products Directive which concerns suspending, revoking or varying a marketing authorisation, ( 15 ) a procedure which is the reverse of that laid down by Article 6(1) of that directive.

29.

According to established case-law of the General Court, the relevant authority must base its decision on ‘new, objective, scientific or medical data’. ( 16 ) In addition, the relevant authority must refer to ‘main reports and scientific expert opinions on which it relies’, whereas the scientific assessment must be ‘based on the most representative scientific theories and scientific positions’. ( 17 )

30.

The General Court then specified the role of judicial review in such a context, stating that it is not the role of the courts to provide their own assessment and effectively substitute that of the relevant authority. Rather, the courts are to review the internal consistency and reasoning of the relevant authority. ( 18 ) Ultimately, ‘the courts may only examine whether the opinion contains a statement of reasons from which it is possible to ascertain the considerations on which the recommendation and opinion are based, and whether it establishes a comprehensible link between the medical or scientific finding and their conclusions’. ( 19 )

31.

Applying these standards to the case at hand, the referring court has already been provided with information that can help in making an assessment of whether the BfArM has in fact consistently and coherently shown that scientific findings concerning one structural analogue are applicable to other analogues as well.

32.

For example, the BfArM’s written observations point to a comprehensive assessment of the scientific data available in the field, concluding that findings concerning the substance BMP can be applied to the substance used by the applicant in the main proceedings (MDN). Studies to this purpose have, according to the BfArM, also been conducted by the German Federal Institute for Risk Assessment.

33.

The referring court may also take into account the fact that the applicant in the main proceedings relied on studies concerning structural analogues to demonstrate to the BfArM the safety of its product in the administrative proceedings stage. Furthermore, the applicant in the main proceedings has referred to products that contain MDN or structural analogues as direct competitors on the market throughout the European Union, which speaks further in favour of a common understanding of a high level of similarity of these substances.

34.

The Commission points out that scientific evidence concerning structural analogues is acceptable only so long as there are no studies concerning specifically the active substance used by the applicant in the main proceedings. Indeed, I agree that this is also in line with the Court’s requirement that the assessment be made according to the present state of scientific knowledge, and with the General Court’s requirement that the findings be new and grounded in the most representative scientific theories and scientific positions.

35.

In light of the foregoing, I am of the view that the relevant authority may use scientific evidence concerning a structural analogue if that is a scientifically recognised method in the present state of scientific knowledge, which it is for the national court to verify.

36.

By its second and third questions, which it is appropriate to examine together, the referring court is asking what effects a product must have in order to be considered to be a medicinal product by function: should the product have direct positive effects on health or may these effects be indirect, for example, by improving appearance and thus increasing self-esteem? In the alternative, is it sufficient in this regard that the product does not have exclusively harmful effects, and is thus not comparable to a narcotic?

37.

In the application of the Medicinal Products Directive, the Court has consistently referred to the products under Article 1(2)(a) as medicinal products by presentation, and to those under Article 1(2)(b) as medicinal products by function. ( 20 ) While it is not impossible that there is a degree of overlap between the two definitions, ( 21 ) the present case concerns more specifically the definition of a medicinal product by function.

38.

In order to reach a conclusion on whether a product meets the definition of a medicinal product by function, the Court stated that an assessment must be made by the relevant authorities (supervised by the courts) on a case-by-case basis, taking into account all the characteristics of the product, in particular its composition, its pharmacological, immunological or metabolic properties, to the extent that these can be established in the present state of scientific knowledge, the manner of its use, extent of its distribution, its familiarity to consumers and the risks its use may entail. ( 22 )

39.

In what follows, then, I will first reflect upon the interpretation of the concept of beneficial health effects – those restoring, correcting or modifying physiological functions (1). Next, I will present my analysis of the role that potential harmful effects of a product play outside the scope of the Medicinal Products Directive (2). Should the Court, however, not agree with my conclusions concerning the beneficial health effects of the product in question, I will also reflect upon the role that potential harmful effects play within the scope of the Medicinal Products Directive (3).

40.

Is the increased growth of eyelashes a beneficial health effect that leads to the conclusion that the product in question is medicinal? To answer this question, it is necessary to delve further into the concept of beneficial effects on human health.

41.

This question has been raised before the Court in numerous borderline cases dealing with possible overlaps between, on the one hand, cosmetic products, ( 23 ) foodstuffs, ( 24 ) medical devices, ( 25 ) as well as narcotics, ( 26 ) and, on the other hand, medicinal products by function.

42.

The Court has already established that a medicinal product by function must have a beneficial effect on human health, and it is insufficient that the product merely modifies physiological functions. ( 27 ) Rather, the Court found that such effects must be appreciable, ( 28 ) significantly affecting the metabolism, ( 29 ) and be genuinely designed ( 30 ) for such a purpose.

43.

Conversely, products which ‘are not such as to entail immediate or long-term beneficial effects for human health’ do not fall within the scope of the Medicinal Products Directive. ( 31 )

44.

The BfArM claims that the decisive criterion for making this determination is whether a product is fit for therapeutic use. Moreover, it argues that the product in question can be used for therapeutic purposes, for example in situations of pathological loss of eyelashes that accompany chemotherapy.

45.

The applicant in the main proceedings argues, however, that the main function of BMP is the treatment of glaucoma, whereas the product in question does not have any effect on it, and should thus not be seen as exerting a beneficial effect on human health.

46.

The Commission underlines that although the function of a medicinal product is not exclusively the treatment of illnesses, a mere effect on appearance is insufficient to meet the standard of ‘modifying physiological functions’ pursuant to Article 1(2)(b) of the Medicinal Products Directive. The Estonian Government adds that the positive effect on appearance and the resulting increase in self-esteem is in fact the main function of cosmetic products.

47.

The product in question alters human appearance by prolonging the growth phase of eyelashes. While the product might, as the referring court suggests, increase self-esteem, I agree with the Commission that it does not significantly affect physiological functions nor does it change the way in which they operate.

48.

The interpretation offered by the respondent in the main proceedings is that the product can be of therapeutic use for conditions that occasionally arise as a result of the treatment of other diseases, such as loss of eyelashes due to chemotherapy.

49.

I do not think that this use suffices to conclude that there is an appreciable beneficial effect on human health. However, it is perfectly possible to use cosmetic products alongside treatments such as chemotherapy to alleviate its undesirable side effects, such as hair loss. ( 32 )

50.

Rather, I think it is possible to compare this product to, for example, tattoo ink or permanent make-up. It would indeed be far-fetched to state that their influence on the appearance of the skin can be characterised as a beneficial effect and as a result classify them as medicinal products by function.

51.

Another consideration, put forward by the BfArM, is the use of an active substance in the serum that is already used in another medicinal product produced for the treatment of a specific disease (glaucoma). Does it matter that the product uses an active substance contained in a product that is already marketed in Germany as a medicinal product?

52.

The Court has dealt with this question in Hecht-Pharma, stating that the use of a substance in a product that can have a physiological effect (because it is used in a medicinal product) does not lead to an automatic classification of such a product as a medicinal product by function. ( 33 ) The relevant authority must, instead, conduct an assessment of each product individually in order to reach a conclusion that the product using the same substance in fact has beneficial effects on human health. ( 34 )

53.

Finally, does the dosage of the active substance in the serum matter in this regard? The Court has previously confirmed that the assessment of the dosage should be made in respect of the normal conditions of use of the product, regardless of the potential effects of a higher dosage. ( 35 ) It is for the national court to verify the composition and the exact percentage of the active substance (given the differences in the submission of the BfArM and the referring court in the order for reference), ( 36 ) and what consequences this has on the conditions of use of the product in question.

54.

Thus, I do not consider that the product in question, by merely inducing the growth of eyelashes, has an appreciable benefit on human health, and it is, consequently, not a medicinal product by function.

55.

In the absence of appreciable health benefits, what is the role of potential harmful effects for the applicability of the Medicinal Products Directive?

56.

None. ( 37 )

57.

In accordance with recital 7 of the Medicinal Products Directive, the harmfulness of medicinal products is to be assessed only in relation to their therapeutic efficacy. In the absence of the latter, we are no longer in the context of the Medicinal Products Directive and harmful effects cannot be dealt with under it. The Court has also confirmed, in respect of narcotics, ( 38 ) that products which are harmful to human health, while having no health benefits, are not medicinal products within the meaning of the Medicinal Products Directive.

58.

Indeed, as was pointed out by Advocate General Bot in respect of narcotics in D. and G., the Medicinal Products Directive cannot be used to penalise the circulation of potentially harmful products that have no therapeutic effects. ( 39 )

59.

Should the relevant authority, in line with the criteria set out in the answer to the first question, demonstrate to the referring court the harmful effects of the product in question, it may be removed from the market in line with the procedure set out in the Cosmetics Regulation. ( 40 ) This might involve action by a number of national authorities that are competent for the subject matter of the Cosmetics Regulation. ( 41 )

60.

To return to the example of tattoo ink and permanent make-up, both these groups of products are currently under assessment as regards their safety. ( 42 ) A number of chemical substances used in these products have also been added to Annexes II and IV to the Cosmetics Regulation. ( 43 )

61.

If the relevant studies find that risks for human health stem also from products inducing eyelash growth, I see no reason why they should not share the same fate as tattoo ink or permanent make-up.

62.

Nevertheless, whether the producer subsequently wishes to develop its product further so that it is safe is a decision it is free to take, protected by the freedom to conduct a business and the free movement of goods.

63.

In conclusion, I consider that the product in question cannot be considered a medicinal product by function without beneficial effects for human health, and any potential harmful effects should be dealt with under the system of the Cosmetics Regulation.

64.

However, if the Court finds that the product in question does have appreciable health benefits, then Article 2(2) of the Medicinal Products Directive excludes the applicability of the Cosmetics Regulation. ( 44 ) In that case, it also becomes relevant to take into consideration potential harmful effects in deciding whether a product can be authorised as a medicinal product. Namely, in such a scenario, therapeutic effects must prevail over harm in order for the product to be allowed to enter the market. ( 45 )

65.

In that respect, it is necessary to point out that, according to the BfArM, scientific evidence concerning analogues to the product in question does not conclude with certainty on the existence of harmful effects.

66.

In such situations of scientific uncertainty, I am of the opinion that it is possible to resort to the applicability of the precautionary principle. This is so because the precautionary principle, as a general principle of EU law, ( 46 ) was applied by the General Court in the context of Article 116 of the Medicinal Products Directive. ( 47 ) This is of particular relevance given that one of the possible reasons for a suspension, revocation or a variation in the marketing authorisation of a medicinal product under Article 116 is the product’s potential harmfulness – an analogous context to the one analysed under this heading.

67.

The Court of Justice defined the precautionary principle as follows: ‘… the assessment which a Member State is required to make may reveal a high degree of scientific and practical uncertainty in that regard. … In such circumstances, it must be acknowledged that a Member State may, under the precautionary principle, take protective measures without having to wait for the reality and the seriousness of those risks to be fully demonstrated’. ( 48 )

68.

The application of the precautionary principle is based on two conditions: ‘first, identification of the potentially negative consequences for health …, and, secondly, a comprehensive assessment of the risk to health based on the most reliable scientific data available and the most recent results of international research’. ( 49 )

69.

More specifically in the context of the Medicinal Products Directive, in GE Healthcare v Commission, the General Court found that the health risks need not be specific, but may also be only potential. In such a scenario, the relevant authority may ‘merely provide serious and conclusive evidence which, without ruling out scientific uncertainty, gives reasonable grounds for doubting the harmlessness of the medicinal product concerned’. ( 50 )

70.

I am therefore of the view that the precautionary principle, as specified by the General Court in the context of Article 116 of the Medicinal Products Directive, can be applied to the routes available to the BfArM in determining the possible harmfulness of the product in question.

71.

It appears to me from the observations of the parties in the main proceedings, which it is for the national court to verify, that the conditions for the applicability of the precautionary principle are met. For example, it was pointed out by the BfArM that concerns about the safety of BMP have also been submitted through RAPEX, the European Rapid Alert System for dangerous products. ( 51 )

72.

Finally, a study of the Scientific Committee on Consumer Safety indicated human health risks associated with the use of prostaglandin analogues to induce the growth of eyelashes. ( 52 ) It should be noted that the preparation of this report was mentioned by the respondent in the main proceedings. However, it was published after the submission of the reference for a preliminary ruling in the present case. Again in the context of a revocation of a marketing authorisation, the Court stated that the national court reviewing such a revocation is not obliged to take into account new scientific evidence that emerged in the meantime. ( 53 ) Nevertheless, in my opinion, this finding does not prohibit the national court from taking such evidence into account in line with national procedural rules.

73.

In conclusion, should the Court find that the product in question does have beneficial effects on human health and the Medicinal Products Directive applies, the relevant authority may resort to the use of the precautionary principle in the face of scientific uncertainty of the harmfulness of the product in question, under the supervision of the referring court.

74.

In light of the foregoing considerations, I propose that the Court answer the questions referred for a preliminary ruling by the Verwaltungsgericht Köln (Administrative Court, Cologne, Germany) as follows: