C-112/02

KOHLPHARMA

OPINION OF ADVOCATE GENERAL TIZZANO delivered o n 11 September 2 0 0 3 1

1. By order of 14 M a r c h 2 0 0 2 , the I — Relevant legislation Oberverwaltungsgericht für das Land Nordrhein-Westfalen (Higher Administra- tive Court of North Rhine-Westphalia), Germany (hereinafter 'the Oberverwal- tungsgericht'), referred a question to the Court for a preliminary ruling regarding the interpretation of Articles 28 EC and 30 EC, 2. It is common knowledge that Article 28 pursuant to Article 234 EC. The national EC prohibits quantitative restrictions on court refers in particular to the situation imports between Member States and all where a proprietary medicinal product measures having equivalent effect. How- imported from a Member State in which it ever, under Article 30 EC, such restrictions is covered by a marketing authorisation is are permitted where they are justified on manufactured on the basis of the same grounds of the protection of health and life active ingredient as that used to manufac- of humans and where they do not constitute ture a proprietary medicinal product which a means of arbitrary discrimination or a is covered by a marketing authorisation in disguised restriction on trade between the Member State of importation. In those Member States. circumstances, the Oberverwaltungsgericht asks whether the competent authority of the latter State may refuse to extend to the imported proprietary medicinal product the marketing authorisation granted for the other proprietary medicinal product on the sole ground that the two proprietary medicinal products do not have a common origin, or whether, under Articles 28 EC 3. Article 3 of Directive 65/65/EEC 2(here- and 30 EC, that authority may refuse that inafter 'Directive 65/65') provides that no marketing authorisation only if, after proprietary medicinal product may be appropriate testing, there are reasonable placed on the market in a Member State doubts that those proprietary medicinal unless a marketing authorisation has been products have different therapeutic effects issued by the competent authority of that or do not offer the same guarantees of State. harmlessness to health.

9. Chiesi Farmaceutici S.p.A. (hereinafter 'Chiesi') sells in Italy the medicinal product 'Jumex', manufactured using the same 7. Like Article 4 of Directive 65/65, Arti- active ingredient, 'selegiline hydrochloride', cles 8 to 11 of Directive 2001/83 set out the used to manufacture 'Movergan', a medic- procedure, documents and particulars inal product marketed in Germany by the necessary for a marketing authorisation to German company Orion Pharma GmbH be granted. (hereinafter 'Orion'). In both cases, the medically active ingredient comes from the same undertaking: the Hungarian company Chinoin. However, while Orion obtains 3 — Directive 2001/83/EC of the European Parliament and of the that active ingredient (directly or through Council of 6 November 2001 on the Community code relating to medicinal products for human use (01 2001 L the Finnish company Orion Corp.) by 311, p. 67). See in particular Article 128 of that directive. virtue of a mere supply agreement with 4 —Council Regulation (EEC) No 2309/93 of 22 July 1993 laying down Community procedures for the authorisation Chinoin, Chiesi obtains that same sub- and supervision of medicinal products for human and veterinary use and establishing a European Agency for the stance under a licensing agreement with Evaluation of Medicinal Products (OJ 1993 L 214, p. 1). Chinoin.

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10. Since the abovementioned medicinal 12. Kohlpharma appealed against that products contain exactly the same active decision to the Obcrverwaltungsgericht, ingredient, Kohlpharma GmbH (hereinafter claiming that the requirement of common 'Kohlpharma'), which wishes to import origin is not a prerequisite for extending to 'Jumex' into Germany, asked the Bundesin­ a proprietary medicinal product imported stitut für Arzneimittel und Medizinpro­ from a Member State a marketing author­ dukte (Federal Institute for Medicinal Pro­ isation already granted in the State of ducts; hereinafter 'the Bundesinstituť) to importation for an — essentially identical extend to that product the marketing — proprietary medicinal product. authorisation which it had already granted for 'Movergan' with regard to the territory of the Federal Republic of Germany.

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the German firm only on the basis of a from a Member State, where it is covered supply agreement with Orion Corp. Fin- by a marketing authorisation, is manufac- land, either directly or via Finland, if, on the tured on the basis of the same active other hand, that authority does not demon- ingredient used to manufacture a proprie- strate in detail as regards either the tary medicinal product which is covered by medically active ingredient or the excipi- a marketing authorisation in the Member ents, which it considers to differ in the State of importation, the competent author- present case both qualitatively and quanti- ity of the latter State may refuse to extend tatively, that the two medicinal products to the first product the marketing author- are not identical, and in particular are not isation that covers the second product on manufactured according to the same for- the sole ground that those proprietary mulation and using the same active ingre- medicinal products do not have a common dient or that they have different therapeutic origin. effects?'

A — Relevant case-law of the Court

HI — Proceedings before the Court 17. Both the national court, in the state- ment of reasons in its order for reference, and the interested parties, in the main proceedings and in the observations sub- 15. Kohlpharma and the Commission have mitted to the Court, made extensive refer- submitted written observations to the ence to the relevant case-law of the Court. I Court. Those parties to the proceedings therefore consider it appropriate to begin and the German Government attended the by summarising that case-law. hearing on 13 March 2003.

19. In Smith & Nephew and Primecrown, regarded as being placed on the market for the national court had asked the Court to the first time (paragraph 21 of the judgment clarify under what conditions a proprietary in Smith & Nephew and Primecrown). medicinal product, which is covered by a m a r k e t i n g a u t h o r i s a t i o n issued u n d e r Directive 65/65 in one Member State, may be covered in another Member State by the marketing authorisation granted in the latter State for another proprietary medic­ inal product. 22. The Court then observed that it had already held in its judgment in De Peijper 7 that the competent authorities of a Member State may not require an importer of a medicinal product lawfully marketed in another Member State to produce all the particulars necessary for the purposes of checking that that medicinal product is 20. The Court stated, first of all, that, since effective and not harmful, if those autho­ the primary purpose of Directive 65/65 is rities possess those particulars in respect of 'to ensure that, when a proprietary medic­ a medicinal product which is 'in every inal product is marketed, public health is respect the same' as the imported medicinal safeguarded by means which cannot hinder product 'or whose differences ļas compared the development of the pharmaceutical with the latter] have no therapeutic effect' industry or trade in medicinal products (paragraph 22 of the judgment in Smith & within the Community', the production of Nephew and Primecrown). all the documents and all the information required by that directive as a pre-condition to the granting of a marketing authorisation is justified, for the purposes of safeguarding public health, 'only in regard to proprietary medicinal products which are being put on the market for the first time' (paragraphs 19 23. The Court therefore pointed out that, and 20 of the judgment in Smith & Nephew although 'the proprietary medicinal pro­ and Primecrown). ducts at issue |in De Peijper] had been manufactured by the same group of com­ panies and therefore had a common origin', the principles asserted in that judgment are applicable also to a situation 'in which independent companies produce proprie­ tary medicinal products, which have a common origin by virtue of the fact that they are manufactured pursuant to agree­ 2 1 . The Court held that 'a proprietary ments concluded with the same licensor' medicinal product covered by a marketing (paragraphs 24 and 25 of the judgment in authorisation in one Member State which is Smith & Nephew and Primecrown). being imported into another Member State as a parallel import of a product already covered by a marketing authorisation in that other Member State' could not be 7 — Case 1 0 4 / 7 5 De Peijper[1976]ECR6 1 3 .

26. However, '[i]f the competent national authority concludes that the proprietary medicinal product to be imported does not satisfy all the abovementioned criteria and B — Considerations of the national court cannot therefore be regarded as having already been placed on the market in the Member State of importation, it cannot issue the new marketing authorisation 29. The Oberverwaltungsgericht doubts required for the marketing of the product whether, in circumstances such as those in to be imported unless the conditions listed this case, the competent authority can I - 3376

KOHLPHARMA

31. Kohlpharma first claims that the crite- rion of common origin, referred to in the judgments in Smith & Nephew and Prime- crown and Rhône-Poulenc Rorer and May & Baker, does not constitute a prerequisite 30. In those circumstances — according to for extending to an imported medicinal the Oberverwaltungsgericht, which refers product a marketing authorisation already to paragraph 26 of the judgment in Smith & granted for another medicinal product in Nephew and Primecrown (see point 24 the State of importation. above) and to the Opinion of Advocate General Geelhoed in Case C-172/00 8— the competent national authority must verify, however, if necessary, in consultation with the competent authorities of the Member State of exportation, whether the imported medicinal product and the product already marketed in the State of importation, although not identical in all respects, are 32. In fact, in Kohlpharma's view, the nevertheless manufactured on the basis of reason why those judgments refer to the the same formulation and using the same common origin of the imported medicinal active ingredients, and have the same product and the product already authorised in the State of importation is that there was a common origin in both cases and, there- fore, the Court mentioned it merely as an 8 — Opinion of Advocate General Geelhoed in Case C-1 72/00 Ferring Arzneimittel (2002) ECR I-6891, points 37 to 40. additional argument.

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35. Kohlpharma continues by submitting 37. The Commission agrees with Kohl- that if the possibility of 'Movergan' and pharma that it is necessary to include cases 'Jumex' having a common origin is ruled such as the present within the concept of out solely because there is a supply agree- common origin. What really matters is that ment between the Chinoin company and the two proprietary medicinal products are the Orion group rather than a licensing essentially identical and that any differences agreement, pharmaceutical undertakings are not significant in terms of the products' safety and efficacy for human health.

9 — In support of that argument, Kohlpharma refers to the Opinion of Advocate General Geelhoed in Case C-172/00 10 — See the judgment in Smith & Nephew and Primecrown, Ferring Arzneimittel, cited above, points 37 to 40. cited above, paragraphs 11 and 14.

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KOHLPHARMA

39. Before addressing the substance of the question referred, 1 must first note that Directive 65/65 was repealed, as were the directives which amended it and other 43. The first is whether the competent directives on medicinal products for human authority of a Member State may refuse to use, by Directive 2001/83. extend to a proprietary medicinal product imported from another Member State a marketing authorisation already granted in the first State for a proprietary medicinal

40. The latter directive, far from amending the substance of the repealed directives, 11 — See the firstrecital in the preamble to Directive 2001/83.

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2. Common origin 50. The first is that the proprietary medic- inal product, which is the subject of parallel importation, must already be covered by a marketing authorisation issued by the 46. As regards this issue, I note once again competent authorities of the Member State t h a t , u n d e r Article 6(1) of Directive of origin (see also point 21 above). 2001/83, no proprietary medicinal product may be placed on the market of a Member State unless it is covered by a marketing 12 — See the judgment in Smith & Nephew and Primecrown authorisation issued by the competent paragraphs 19 and 20, cited above in points 20 and 21 To the same effect, see the Opinion of 12 December 2002 authority of that State in accordance with delivered by Advocate General Jacobs in Case C-15/01 Paranova Läkemedel [2003] ECR I-4175, paragraph 6, the conditions laid down by that directive. where there are further references.

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54. I do not share that view. It is certainly true that, in Smith & Nephew and Prime- crown, the Court pointed out that the 52. While Kohlpharma and the Commis- imported proprietary medicinal product sion consider that those factors are in and the reference product in the State of themselves sufficient to classify the impor- importation had a common origin (see tation of medicinal products as a parallel point 23 above). import falling outside the scope of Directive 2001/83, the German Government main- tains that a further condition must be fulfilled. According to that Government, as has been noted, the imported proprietary medicinal product and the product mar- keted in the Member State of importation 55. That does not mean, however, as Kohlpharma has rightly observed, that the Court considered that factor to be decisive for the purposes of establishing whether the 13 — The pharmaceutical form of a medicinal product means the form in which it is presented (capsules, drops to be taken import was a parallel import falling outside orally in solution, injections and so on) and the form in the scope of Directive 2001/83. which it is administered (orally, rectally, nasally, cuta- neously and so on). On this subject, see point 37 of the Opinion of Advocate General Ruiz-Jarabo Colomer in Case C-368/96 Generics (UK) and Others [1998] ECR I- 7967. 14 — '[T]wo medicinal products are bioequivalents if they are pharmaceutical equivalents or alternatives and if their bioavailabilities (rate and extent) after administration in the same molar dose are similar to such a degree that their effects, with respect to both efficacy and safety, will be essentially the same' (judgment in Generics, cited above, 56. Indeed, on closer examination, it is paragraph 31). 15 — See, in this regard, the judgment in Generics, cited above, apparent that, in that judgment, the Court paragraph 36. referred to the common origin of the

59. It seems to me that that wording, in particular the use of the word 'moreover', supports the view that common origin is a 57. Secondly, the Court referred to that factor which, while certainly being impor- factor because the common origin of the tant, is none the less supplementary and imported medicinal product and of the additional to the — decisive — factor of the 'national' product is at any rate a reliable identical or essentially identical nature of indication that the two products are essen- the products. tially identical, a fact which the parallel importer may rely on before the competent authority of the Member State of importa- tion in order to avoid application of Directive 2001/83 (see point 82 below). 60. In my view, similar considerations apply also in relation to paragraph 28 of the judgment in Rhône-Poulenc Rorer and May & Baker already cited (see point 27 above), which could equally be interpreted as proving that the Court considers the decisive condition to be the common origin of the imported medicinal product and the product already marketed in the State of 58. However, the fact that common origin importation. does not constitute an essential requirement for the purposes of the present case is, in my view, also apparent from the very wording of the judgment in Smith & Nephew and Primecrown. In paragraphs 21 to 24 of that judgment, after stating that 'the provisions 61. In actual fact, it seems to me that that of Directive [2001/83] concerning the pro- passage has a different meaning. In it, as cedure for issue of marketing authorisations Kohlpharma has observed, the Court cannot apply' to a case such as that examined in De Peijper, where the proprie- tary medicinal product which was the 16 — Emphasis added. subject of a parallel import 'was in every 17 — Emphasis added.

65. Therefore, what is above all clear from that case-law is that the principal aim of the relevant Community legislation is to safe- guard public health. Indeed, that is why the production of all the documents and all the 62. For the reasons set out above, I do not, information necessary for the granting of a therefore, consider that the Court's case- marketing authorisation is justified 'only in law lays down the condition at issue, regard to proprietary medicinal products unequivocally and unambiguously, and, which are being put on the market for the consequently, that condition cannot con- first time' (paragraphs 19 and 20 of the clusively be relied on in support of the judgment in Smith & Nephew and Prime- German Government's view. crown), just as parallel imported proprie- tary medicinal products may be placed on the market in a Member State without being subject to the requirements laid down by that legislation only where those pro- ducts do not pose any risk to human health and life (see points 23 and 24 above). 63. However, in my opinion, there are arguments which counter that view and which can be inferred from the exact same case-law of the Court to which considerable reference is made here.

66. However, if the main criterion must be the protection of public health, I do not believe that common origin can play a 64. As already mentioned, that case-law decisive role in this case. places considerable emphasis on the fact that the primary purpose of Directive 2001/83 is 'to ensure that, when a proprie- tary medicinal product is marketed, public 18 — Judgment in Smith & Nephew and Primecrown, cited above, paragraph 19. To the same effect, see judgment in health is safeguarded by means which Generics, cited above, paragraph 22.

72. Consequently, it seems to me that the 69. I would add that, in my opinion, the conclusion can be drawn, with regard to other requirement highlighted by the this case, that the fact that the two Court's case-law, that is to say the require- ment not to hinder 'the development of the pharmaceutical industry or trade in medic- inal products within the Community' (see 19 —Those recitals state: '[t]he essential aim of any rules governing the production, distribution and use of medic- point 20 above), is also better safeguarded inal products must be to safeguard public health ... by means which will not hinder [the free movement or] by the premiss which does not require the medicinal products within the Community'.

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proprietary medicinal products in question cal, or whether, where there is sufficient have been manufactured on the basis of a evidence in that regard, it is for the licensing agreement or a supply agreement competent authority of the State of impor- with the same undertaking cannot be tation to carry out any investigations regarded as crucial when it comes to necessary before it can adopt a decision placing on the market the medicinal pro- on the application for the marketing duct which is the subject of a parallel a u t h o r i s a t i o n to be extended to the import into the Federal Republic of Ger- imported proprietary medicinal product. many.

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is subject to a burden of proof similar to medicinal product, but that data has pre- that incumbent on manufacturers — such sumably already been supplied to the as, for example, manufacturers of generic competent authority of the State of expor- medicinal products — wishing to rely on tation by the holder of the marketing the procedure laid down in Article 10 of authorisation in that State. Directive 2001/83, that is to say the duty to prove by means of bioavailability studies that the medicinal products which they intend to place on the market are bioequi- valent to medicinal products already on that market. 79. In principle, however, a manufacturer of generic medicinal products places on the market of one or more Member States medicinal products which are not yet covered by a marketing authorisation in 77. Moreover, according to the Commis- any Member State, and, consequently, he sion, the slighter the degree of common alone possesses information on their safety origin between two medicinal products, and efficacy. It therefore seems clear to me that is to say the weaker the link between that such a manufacturer should be the holders of the marketing authorisations required to fulfil all the conditions laid issued for those medicinal products in the down by Directive 2001/83 where he seeks two Member States, the greater should be to avail himself of the abridged procedure the burden on the importer to prove that provided for by Article 10 of that direc- those medicinal products are so similar tive. 20 that, in the event of the importation of one of those products into one or other of those States, the application of Directive 2001/83 would not be justified.

lack of significant differences, in terms of mation in his possession or accessible to safety and efficacy, between the imported him. However, in my view, any additional proprietary medicinal product and the information necessary to establish the reference product in the State of importa- safety and efficacy of the imported proprie- tion can be found in the package leaflets of tary medicinal product should be sought those proprietary medicinal products. first and foremost by the competent author- Under Article 59 of Directive 2001/83, ity of the Member State of importation those leaflets should include: a full state- using, as Kohlpharma points out, all the ment of the active substances and excipients means at its disposal and, in particular, in of the medicinal product expressed qualita- consultation with the competent authority tively, a statement of its active substances of the Member State of exportation. 21 expressed quantitatively, the pharmaceuti- cal form, the therapeutic indications, the information necessary for taking it (contra- indications, precautions for use and special warnings), the dosage, the method and frequency of administration and the unde- sirable effects.

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85. That is true also because, again accord- 88. If, having carried out the appropriate ing to the Court, 'simple cooperation investigations, doubts persist as to the between the authorities of the Member safety and efficacy of the proprietary States would enable them to obtain the medicinal product in question, only then necessary substantiating documents on a can that authority require the importer to reciprocal basis' regarding the safety and provide proof capable of dispelling those efficacy of the imported medicinal pro- doubts and thus avoiding the marketing of duct. 23 the imported proprietary medicinal product being made subject to the conditions laid down by Directive 2001/83.

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V — Conclusion

90. In the light of the foregoing considerations, I therefore propose that the Court- reply to the question raised by the Oberverwaltungsgericht as follows:

(1) Article 28 EC precludes a national authority from obstructing the parallel importation of a proprietary medicinal product which is covered by a marketing authorisation in the Member State of exportation and which, although it is not identical to a proprietary medicinal product authorised in the Member State of importation and does not have a common origin with that product, contains, qualitatively and quantitatively, the same active ingredients, has the same pharmaceutical form, is bioequivalcnt and does not appear, in the light of scientific knowledge, to present significant differences as regards safety and efficacy.

(2) Where, despite information provided by the importer, serious doubts persist as to the lack of significant differences between a proprietary medicinal product imported from a Member State, in which it is lawfully marketed under a marketing authorisation issued by the competent authority of that State, and a proprietary medicinal product placed on the market in the Member State of importation, the competent authority of the latter State can require that the imported proprietary medicinal product be placed on the market subject to full compliance with the conditions laid down by Directive 2001/83 only after it has itself carried out all the appropriate investigations, including consultation with the competent authorities of the Member State of exportation.