C-15/01

PARANOVA LÄKEMEDEL AND OTHERS

OPINION OF ADVOCATE GENERAL JACOBS delivered on 12 December 2002 1

1. These cases raise a number of questions principally governed by Council Directive concerning the consequences for a parallel 65/65/EEC of 26 January 1965 on the importer of medicinal products benefiting approximation of provisions laid clown by from a marketing authorisation in the law, regulation or administrative action Member State of import where that auth- relating to medicinal products. 3 orisation is withdrawn at the request of the company holding it.

4. Article 3 of Directive 65/65 provides that no medicinal product may be placed 2. Case C-15/01 Paranova Läkemedel AB on the market of a Member State unless a is a reference from the Swedish Regerings- marketing authorisation has been issued by rätten (Supreme Administrative Court); the competent authorities of that Member Case C-l 13/01 Paranova Oy is a reference State or an authorisation has been granted from the Finnish Högsta Förvaltningsdom- in accordance witli Regulation (EEC) stolen (Supreme Administrative Court). No 2309/93. 4

5. Article 4 of Directive 65/65 defines in The Community legal context detail the procedure, documents and infor- mation necessary for the issue of a market- ing authorisation by the competent auth- ority of a Member State.

6. It is clear from the case-law of the Court Those rules, as interpreted by the Court, that parallel imports of medicinal products mean in particular that an operator who are not covered by Directive 65/65. That has bought a medicinal product lawfully case-law was recently summarised by the marketed in one Member State under a Court in Ferring 5as follows: marketing authorisation issued in that State can import that medicinal product into another Member State where it already has a marketing authorisation without having to obtain such an authorisation in accord- ance with Directive 65/65, and without having to provide information about the verification, prescribed by the directive, of 'According to the principles laid down in efficacy and non-toxicity of the medicinal Directive 65/65, no medicinal product may product. It is not necessary for the pro- be placed on the market for the first time in tection of public health to subject parallel a Member State unless a marketing auth- importers to such requirements, as the orisation has been issued in accordance competent authorities of the Member State with the directive by the competent auth- of importation already have all the infor- ority of that State. Applications for market- mation necessary to carry out that verifi- ing authorisations for a medicinal product cation (see in particular Case 104/75 De submitted by the person responsible for Peiįper [1976] ECR 613, paragraphs 21 placing it on the market must contain the and 36, and Case C-201/94 Smith Sc information and be accompanied by the Nephew and Primecrown [1996] ECR documents listed in Article 4 of the direc- 1-5819, paragraph 22). tive, even where the medicinal product concerned is already the subject of an authorisation issued by the competent authority of another Member State (Case C-94/98 Rhône-Poulenc Rorer and May Sc Baker [1999] ECR 1-8789, paragraph 23). In such a case the parallel import is auth­ orised in the State of importation by reference to the marketing authorisation issued in accordance with Directive 65/65 ('marketing authorisation of reference').'

imports. The Commission recognised that to set up a pharmacovigilance system practice in its guidelines6 published in which, among other things, imposes obli- 1982, subject to limitations designed to gations on the holder of a marketing auth- ensure that the inevitable restrictions on orisation relating to the registration and imports flowing from any monitoring sys- notification of all adverse reactions to those tem are justified for the purpose of pro- medicinal products on humans. To that end tecting the health and life of humans reports must be submitted to the competent pursuant to Article 30 EC. Thus for authorities at regular intervals and must be example the Commission envisages that accompanied by a scientific evaluation. the parallel importer may be required to supply the competent authorities of the Member State of import with information enabling them to check that the medicinal product to be imported is in fact covered by the marketing authorisation of reference relied on by the parallel importer.

The proceedings before the national courts

8. In the context of such a system, many Member States — including, it appears 10. Both cases concern the medicinal prod- from the orders for reference, Sweden and uct Losec. Losec, reportedly the world's Finland — issue separate authorisations to largest-selling pharmaceutical, is used to parallel importers. For convenience, I shall treat and prevent peptic ulcers and reflux refer to such an authorisation as a 'licence' oesophagitis (heartburn). It contains ome- or 'parallel import licence', as distinct from prazole, a substance called a proton-pump the 'marketing authorisation' within the inhibitor which works by blocking a par- meaning of Directive 65/65 for the refer- ticular mechanism in the stomach called the ence product. proton pump which controls acid produc- tion, thereby reducing the amount of stom- ach acid produced.

14. The Läkemedelsverket gave notice to Paranova that the manufacturers' market- ing authorisations for the capsules were no longer valid and that as a consequence and in accordance with the relevant national 12. Subsequently Hässle and Astra ('the regulations Paranova's parallel import manufacturers') each gave notice to the licences were also no longer valid. relevant national medical products agency (the competent authority for the purpose of Directive 65/65, in each case called the Läkemedelsverket) that it was withdrawing Losec capsules from the market and at the same time surrendering or seeking revoca- 15. Paranova sought annulment of the tion of the marketing authorisation for decisions of the Läkemedelsverket on the those products. ground that, inter alia, they were incom- patible with Articles 28 and 30 EC. The application was made in the Swedish case to the Länsrätten (County Administrative Court), Uppsala, with an appeal to the Kammarrätten (Administrative Court of Appeal), Stockholm, and thence to the referring court and in the Finnish case directly to the referring court. 13. The reason for the manufacturers' actions was that they intended to sell a new variant of Losec called Losec MUPS tablets. The capsules however were to continue to be sold in other Member States under authorisations granted there. It appears to be accepted that Losec MUPS 16. The Läkemedelsverket is in each case of tablets and Losec capsules are what are the view that the fact that there is no known as therapeutic equivalents —• that is marketing authorisation for the capsules in to say, they contain the same active the Member State of importation (Sweden ingredient (omeprazole) — and are bioequi- or Finland) means that capsules cannot valent in that that ingredient is absorbed by lawfully be imported by parallel trade from the body at the same rate and to the same another Member State since in such cir- extent when taken orally. They differ cumstances it would be unable properly to however according to the Läkemedelsver- comply with its duty of pharmacovigilance.

2. If Community law imposes restrictions or conditions on the right of a national agency to decide that a marketing auth- orisation for parallel imports comes to an 2. If the parallel importers rely on a new end in the situation referred to in Question marketing authorisation for a directly 1, what importance should be accorded to imported medicinal product rather than the facts that on the old marketing authorisation, is authorisation for the continued marketing of the medicinal product imported as a parallel import precluded by the fact that that medicinal product and the directly imported medicinal product which is (a) the holder of the original marketing covered by the new marketing authori- authorisation has obtained a new mar- sation are different in the sense that the keting authorisation for a medicinal

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OPINION OF MR JACOBS — CASES C-15/01 AND C-113/01

product designed to replace the original adapt his activity? Do any of the circum- medicinal product but that new prod- stances referred to in Question 2 affect the uct is not in the same pharmaceutical question whether it may be decided that the form (tablets instead of capsules) and marketing authorisation for a parallel the active ingredient is not exactly the import expires immediately?' same (magnesium Omeprazole instead of Omeprazole); on the other hand, the national agency considers that the medicinal products are bioequivalent and that they have the same thera- peutic effect;

The recent case-law of the Court

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PARANOVA LAKEMEDEL AND OTI Iľ.RS

relating to the protection of public health in ation with the national authorities of the accordance with Article 30 EC. It stated other Member States by means of access to that the principle of proportionality, which the documents and data produced by the was the basis of the last sentence of manufacturer or other companies in the Article 30 EC, required that the power of same group relating to the old version in the Member States to prohibit imports of the Member States in which that version products from other Member States be was still marketed on the basis of a restricted to what was necessary in order marketing authorisation still in force. 11 to achieve legitimately pursued aims con­ cerning the protection of health. National legislation or practice could not therefore benefit from the derogation laid down in Article 30 EC when the health and life of humans could be protected equally effec­ 23. The Court accordingly concluded that tively by measures less restrictive of intra- national legislation under which the with­ Community trade. 9 drawal of the marketing authorisation of reference for a medicinal produci on appli­ cation by the holder thereof meant that a parallel import licence for that product automatically ceased to be valid did not comply with Article 28 EC. 12

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OPINION OF MR JACOBS — CASES C-15/01 AND C-l 13/01

Observations of the parties 28. In my view, that question has now been answered in the negative by the judgment of the Court in Ferring for the reasons summarised above. 14 25. Written observations have been sub- mitted in the Swedish case by Paranova AB, the Danish, Netherlands, Norwegian and Swedish Governments and the Commission and in the Finnish case by the Danish, Finnish, Netherlands and Norwegian Gov- 29. In the Swedish case the referring court ernments and the Commission. Paranova, asks in addition whether the answer to that all the aforementioned governments and question depends on what specific reasons the Commission were represented at the have given rise to the request by the holder hearing, which was common to both cases. of the marketing authorisation of reference for the withdrawal of that authorisation.

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PARANOVA LAKEMEDEL AND OTHERS

depends on whether the holder of the orisation in the Member State of import- marketing authorisation of reference (or ation, who belongs to the group of com- companies belonging to the same group) panies which is in possession of the market- continues to sell the product which is the ing authorisations for the old version in the subject of parallel imports — namely the other Member States, to supply the necess- capsules — in other Member States on the ary information'. It is clear from the basis of marketing authorisations granted context 17 that the Court was responding there. to the argument that the pharmacovigilance system would not work where a marketing authorisation of reference was revoked since the obligation on the holder of that authorisation to submit information regu- larly as required by Directive 75/319 would also lapse, so that the competent authorities in the State of import could not be sure that 32. It is not entirely clear what has the use of the old product imported in prompted the Swedish referring court to parallel was still safe according to the latest raise that point. In one sense, it seems scientific data. The Court must therefore irrelevant, since the phenomenon of paral- have meant in the passage cited above that lel import pre-supposes that the imported it was possible to compel the holder of the product is on the market in at least one marketing authorisation for the new ver- Member State other than the State of sion of the product in the Member State of import; that product will moreover fre- import, who belongs to the group of quently have been placed on the other companies which is in possession of the market by the holder of the marketing marketing authorisations for the old ver- authorisation of reference or a company sion in the other Member States (including belonging to the same group. The Swedish ex hypotbesi the State of export), to supply court may however be asking whether the the necessary information relating to the situation there described will make the old version. pharmacovigilance duties of the competent authority of the State of import easier to discharge where a parallel import licence survives revocation of the marketing auth- orisation of reference.

paragraphs 39 to 45 below, in the context Article 30 EC must respect the principle of of the second question referred by the proportionality. Paranova Oy argued that Finnish court which directly raises this that assessment must be made with regard issue. to the circumstances of the case in question. It stressed that the fact that the products were, in principle, identical and that they were well known, both to national agencies in charge of evaluation of medicinal prod- ucts in the European Union and to doctors and patients, had to be taken into account and that Losec capsules, having been avail- able on the world market for some time and being one of the most widely sold The second question referred in the Finnish medicines, had been used by such a sig- case nificantly large number of people and for such a significant period of time that national agencies in charge of evaluation of medication in the European Union had been able to develop a very clear opinion of how they worked and their effects. 35. The referring court in the Finnish case also asks in effect whether it is relevant that (a) the holder of the marketing authori- sation of reference has obtained a new marketing authorisation for a replacement product which, albeit in a different phar- maceutical form and with a slightly dif- ferent active ingredient, is regarded as bioequivalent and as having the same therapeutic effect; (b) subsequent control of the effectiveness and safety of the product may be more difficult because the marketing authorisation of reference has been withdrawn; and (c) the imported 37. Under (a), the Finnish referring court product has been widely used over many asks whether it is relevant that the holder of years so that it is unlikely to present a the marketing authorisation of reference danger to public health. has obtained a new marketing authori- sation for a replacement product which, albeit in a different pharmaceutical form and with a slightly different active ingredi- ent, is regarded as bioequivalent and as having the same therapeutic effect. In my view, that factor is not relevant given the conclusion of the Court in Ferring, since in 36. It appears from the order for reference any event the competent authority of the that Paranova Oy raised those points Member State of import is not entitled to before the referring court in the context of revoke the parallel import licence unless its argument that a prohibition on imports there is a demonstrated risk to public based on health reasons in accordance with health.

38. Under (b), the Finnish referring court determination by the competent authority mentions possible problems with phar- of the existence and reality of the risk must macovigilance. It is concerned in particular in my view be substantiated: the mere that subsequent control of the effectiveness assertion by the competent authority con- and safety of the product may be more cerned that, for example, it would not be difficult after revocation of the marketing possible to carry out the necessary safety authorisation of reference. checks if parallel imports of the capsules continued after revocation of the marketing authorisation of reference would not be sufficient if the authority could not demon- strate that that concern was justified. 39. The Court made it clear in Ferring that if it can be demonstrated that there is in fact a risk to public health arising from the coexistence on the market of the Member State of import of the two versions of the medicinal product at issue (in the present case, the capsules and the tablets), such a risk may justify restrictions on the import- ation of the old version. 18 That statement was restricted to the specific alleged health risk referred to in the questions referred in that case. It is however clearly of broader application. If therefore it can be demon- strated that there is in fact a risk to public health arising from the continued market- ing of the imported capsules in Finland after withdrawal of the marketing auth- orisation of reference, restrictions on import may be justified. 4L In that context, it is worth repeating the points made by the Court in Ferring. First, it gave weight to the fact that the old version of the medicinal product continued 40. However, the Court added in Ferring to be lawfully marketed in the Member that the question of the existence and the State of exportation under the marketing reality of the risk is a matter which is authorisation issued in that State. Second, it primarily for the competent authorities of noted that, although adequate monitoring the Member State of import to determine, of the old version remained necessary in the and the mere assertion by the holder of the State of import, pharmacovigilance satisfy- marketing authorisation for the new and ing Directive 75/319 could ordinarily be old versions that there is such a risk is not guaranteed through cooperation with the sufficient to justify prohibition of the national authorities of the other Member importation of the old version. 19 The States by means of access to the documents and data produced by the manufacturer or other companies in the same group, relating 18 — Paragraph 43 or the judgment. to the old version in the Member States in 19 — Paragraph 44 of the judgment. which that version was still marketed on

42. At the time of the events giving rise to the main proceedings in the present cases, 23 Chapter Va of Directive 75/319 24 as amended in particular by Directive 93/39 25 imposed a series of obligations concerning pharmacovigilance. In particu- lar, Article 29a required Member States to establish a pharmacovigilance system to be 43. With effect from 30 June 2000, those used to collect information useful in the obligations have been further strengthened surveillance of medicinal products, with by Directive 2000/38, 27 which amended particular reference to adverse reactions in Chapter Va of Directive 75/319. The mar- human beings, and to evaluate such infor- keting authorisation holder must now in mation scientifically. Articles 29c and 29d addition provide to the competent auth- required the person responsible for placing orities any other information relevant to the medicinal product on the market to the evaluation of the benefits and risks of a establish and maintain a system ensuring medicinal product, including appropriate that information about all suspected information on post-authorisation safety adverse reactions reported to the company studies, 28 maintain detailed records of all and to medical representatives was col- suspected adverse reactions occurring lected and collated at a single point within either in the Community or in a third the Community, to answer fully and country 29 and record and promptly report promptly any request from the competent to the competent authority of the Member authorities for additional information State in whose territory the incident necessary for the evaluation of the benefits occurred all suspected serious adverse reac- and risks of a medicinal product and to tions of which he has or can reasonably be record and promptly report to the compet- expected to have knowledge. 3 0 Fur- thermore, Member States are to ensure that reports of suspected serious adverse 20 — Paragraphs 36 and 38 of the judgment, citing Rhône- Poulenc Rorer and May & Baker, paragraph 46. 21 — See paragraph 33. 26 — Cited in note 4. 22 — Rhône-Poulenc Rorer and May & Baker, cited in para- 27 — Cited in note 7. graph 6, paragraph 46 of the judgment. 28 — Article 29c(d). 23 — 1998. 24 — Cited in note 7. 29 —Article 29d(1). 30 — Article 29d(2) and (3). 25 — Cited in note 3.

44. The Finnish Government stated at the hearing that reliance on the pharmacovigi- lance requirements of Directive 75/319 was undermined by the fact that different Member States used different languages: a 46. Finally, the factor referred to by the report of a suspected serious adverse reac­ Finnish referring court at (c) — namely the tion which took place in Greece, for history of widespread use of the capsules — example, would be forwarded to the Finn­ is essentially part of the same phar­ ish competent authority in Greek. I am not macovigilance point: although there is no however convinced that that is as serious a formal requirement that the competent problem as it may appear at first sight. The authority of the Member State of import 'Note for Guidance on Procedure for take such a factor into account, it will Competent Authorities on the Undertaking inevitably mean that the recording and of Pharmacovigilance Activities' 32 issued reporting system imposed by the legislation by the Agency requires that the terminol­ and summarised above 33 is unlikely to be ogies used to code medicinal products, triggered. diseases and adverse drug reactions should ensure compatibility of reports between Member States and in particular that reports entered into a database should be coded according to internationally approved terminologies or with mutually accepted terms enabling connections with internationally approved terminologies. 47. I accordingly conclude on the Finnish court's second question that, where a marketing authorisation of reference has been withdrawn for reasons unconnected with the safety of the product, restrictions on the continued import of medicinal 45. In my view the combined effect of the products previously imported as parallel abovementioned pharmacovigilance imports will be justified only if it can be requirements is such that it would be only demonstrated that there is in fact a risk to in exceptional cases that the competent public health arising from the continued marketing of the imported capsules in the Member State of import. 31 — Article 29f(2). 32 — CPMIVPhVWP/175/95 issued in June 1995; sec nar.lRranh 3.1.4. 33 — See paragraphs Ί 2 anil 43.

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