C-120/97

O P I N I O N OF MR LÉGER — CASE C-120/97

OPINION OF ADVOCATE GENERAL LÉGER delivered on 9 June 1998 *

1. Does Council Directive 65/65/EEC of The Community law framework 26 January 1965 on the approximation of pro- visions laid down by law, regulation or admin- istrative action relating to proprietary medic- inal products 1 require Member States to adopt specific procedural rules in regard to legal 3. Medicinal products, given their specific proceedings brought against a decision nature, have been the subject of very close revoking a marketing licence for a propri- attention by the Community legislature, which etary medicinal product (otherwise known as has been reflected in the adoption of a com- a 'medicinal product for human use' or a plex but coherent body of harmonising direc- 'medicinal product') delivered by the compe- tives, of which Directive 65/65 remains the tent national authority? That, in substance, is basic text. The objective pursued has been the question which the Court of Appeal, twofold: to safeguard public health 3 while at London, has submitted to the Court. the same time bringing about progressively the free movement of medicinal products for human use. 4

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U P J O H N y LICENSING AUTHORITY

and protocols" directive') 6 and 75/319, 7 as health, Directives 75/318 and 75/319 supple- amended by Council Directive 83/570/EEC mented the provisions laid down by Direc- of 26 October 1983. 8 tive 65/65.

8. These directives require the national author- 5. Under this system, the competent authority ities to process applications for marketing in the matter of marketing licences for medic- licences in accordance with the protocols inal products for human use ('the authority' described in the annex to the 'standards and or 'the national authority') is essentially protocols' directive. Medicinal products placed national. on the market are thus subject to controls carried out in accordance with harmonised methods and by experts with specific tech- nical and professional qualifications.

6. Article 3 of Directive 65/65 provides that no proprietary medicinal product may be placed on the market in a Member State unless an authorisation has been previously issued 9. Article 4 of Directive 65/65, as amended by the competent authority of that State. The by Directives 75/318, 75/319 and 83/570, marketing licence thus issued is valid only in defines precisely the procedure to be followed the territory of the issuing State. A new mar- and what must feature in the documentation keting licence is necessary and must be to be submitted in support of an application obtained in each State within the territory of for a marketing licence. This documentation which the medicinal product is marketed. must, inter alia, contain the results of specific tests intended to establish the quality, safety and efficacy of the medicinal product.

13. Those grounds are set out in Article 11 of Directive 65/65, as amended by Directive 83/570, which states that: 'The competent authorities of the Member States shall sus- 15. Finally, these harmonising directives intro- pend or revoke an authorisation to place a duce several mutual recognition factors into proprietary medicinal product on the market the Community pharmaceutical legislation. where that product proves to be harmful in This is the case with regard to Article 8 et the normal conditions of use, or where its seq. of Directive 75/319, as amended by Direc- therapeutic efficacy is lacking, or where its tive 83/570, which set in place a consultation qualitative and quantitative composition is procedure through the intervention of a Com- not as declared. Therapeutic efficacy is lacking munity body, the Committee for Proprietary when it is established that therapeutic results Medicinal Products. cannot be obtained with the proprietary product.

16. Under Article 8 of Directive 75/319, as An authorisation shall also be suspended or amended, the purpose of this Committee is revoked where the particulars supporting the '... to facilitate the adoption of a common application as provided for in Articles 4 and position by the Member States with regard to 4a are incorrect ... or when the controls [car- decisions on the issuing of marketing autho- ried out on the finished product, on the com- risations and to promote thereby the free ponents and intermediary products in the movement of proprietary medicinal products manufacture under harmonised methods by

23. The Committee for the Safety of Medi- cines ('the CSM') is a body which the 19. Article 14(3) provides that: 'The Member Licensing Authority must consult in proceed- State(s) concerned shall decide what action to take on the Committee's opinion within 60 days of receipt of ... [the Committee's opin- 9 — Section 19. ion]. They shall immediately inform the Com- 10 — Section 20(1) of the 1968 Act, as amended by SI 1977/1050, mittee of their decision'. regulation 4(3).

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ings relating t o the suspension, revocation or cannot determine whether the scientific judg­ variation of a marketing licence. ment of the Licensing Authority was well founded or whether the scientific evidence adduced was relevant; it may state only whether, in deciding to revoke the licence in question, the Authority committed a manifest error in the appraisal of the facts. 24. The Medicines Commission is also a body responsible for advising the Licensing Authority in relation to licences and certifi­ cates concerning proprietary medicinal prod­ ucts.

27. It is precisely this limitation on the powers of review which the national courts can exer­ cise over the acts of an administrative authority 25. Pursuant to the national legislation in that forms the subject-matter of the reference force, when the Licensing Authority is con­ for a preliminary ruling. sidering revoking a marketing licence, an administrative phase is instituted in which the holder of the marketing Učence may argue his case and, in particular, submit any relevant documentation and be assisted by experts of his choosing in order to establish that the medicinal product which the authorities are Facts, procedure and questions referred for a investigating possesses the characteristics preliminary ruling required by Directive 65/65 (safety, thera­ peutic efficacy and quality).

29. In July 1991 the MCA had its attention drawn to a case in the United States in which 31. However, through the MCA, the a woman had killed her mother while under Licensing Authority informed Upjohn on the influence of Triazolam. After obtaining 17 July 1992 of its intention to proceed with the opinion of the CSM and the Medicines the definitive revocation of all marketing Commission, 12 the M C A informed Upjohn licences for Triazolam and stated that it had on 2 October 1991 that the Licensing taken account of the Committee's opinion of Authority had decided to suspend the Triaz- 11 December 1991. The Licensing Authority olam marketing licences for three months. also informed Upjohn that, in accordance That provisional suspensory decision was with the national legislation in force, it was renewed at three-monthly intervals. entitled, inasmuch as the Licensing Authori- ty's view differed from that of the Medicines Commission, to appeal to the 'Person Appointed' or 'Persons Appointed'. The report by the Persons Appointed concluded that the benefits of Triazolam in dosages of 30. In parallel to the national procedure and 0.25 mg and 0.125 mg outweighed the risks. in accordance with the second paragraph of Article 11 of Directive 75/319, as amended by Directive 83/570, the French Republic and the Kingdom of the Netherlands referred the matter to the Committee for Proprietary Medicinal Products ('the Committee') in October 1991. The opinion of the Committee, 32. O n 9 June 1993, however, the Licensing delivered on 11 December 1991, was itself not Authority informed Upjohn of its decision to in favour of total revocation of the marketing revoke all marketing licences for Triazolam licence, and the Committee invited an ad hoc with immediate effect. It set out the detailed rapporteurs' group to supplement its opinion reasons for its decision of revocation and also by assessing the relative risk-benefit ratios of explained why it had rejected the conclusions all short-acting hypnotics (including Triaz- of the Persons Appointed, particularly on the olam). At its meeting on 14 and 15 September issues of dose equivalence and safety margins. 1993 the Committee adopted that group's report, which had concluded that Triazolam administered in authorised dosages did not appear to involve unacceptable risks that were

O n the true construction of Council Direc- tive 65/65/EEC as amended and in the light of Community law generally, is it the duty of 34. Upjohn takes the view that the judicial a national court when ruling upon the com- procedure in force in the United Kingdom is patibility with the aforesaid Community law contrary to Community law, which, in its of a decision of a Licensing Authority of a opinion, requires Member States to institute Member State to revoke a licence held by the a procedure for judicial review of decisions manufacturer of a medicine product to decide taken by national authorities enabling national whether or not the said decision was the cor- courts to verify the reliability of the scientific rect decision as opposed to a decision which evidence on which the administration bases the Licensing Authority could reasonably its decision to revoke marketing licences, and have reached on the material before it? thus to assess afresh the issues of fact and law and to rule, in particular, on whether the decision taken is 'correct' 13 and complies with the principle of proportionality.

Question 2

35. By order of 3 February 1995, the High Court rejected that preliminary request. O n If the answer to Question 1 is that the national appeal, however, the Court of Appeal formed court has to decide whether the decision of the view that it was necessary for the Court the competent authority was the correct deci- of Justice to resolve this preliminary issue sion does Community law require it to answer before the merits of the case could be exam- that question solely on the basis of the mate- ined. rial before the Competent Authority or is it obliged to look at any relevant material coming to light after the decision?

40. Article 12 of Directive 65/65, in contrast, The first question provides that it is for the domestic legal order of each Member State to regulate such arrange- ments. Article 12, it should be recalled, pro- vides that: 'All decisions taken pursuant to Articles 5 ... or 11 shall state in detail the rea- sons on which they are based. A decision 37. By its first question, the Court of Appeal shall be notified to the party concerned, who is asking the Court to determine whether shall at the same time be informed of the Directive 65/65, or Community law more remedies available to him under the laws in generally, requires Member States to intro- force and of the time-limit allowed for the duce a procedure for judicial review of deci- exercise of such remedies'. 14 sions taken by national authorities that enables the competent national courts to substitute their assessment for that of the national author- ities. The Court of Appeal is specifically unsure as to whether Directive 65/65 requires it to verify the relevance of the scientific evi- 41. Directive 65/65 cannot therefore be con- dence adduced by the Authority in support strued as imposing on Member States an obli- of its revocatory decision. gation to establish a procedure for judicial review of decisions taken by national authori- ties under which the competent national courts would be empowered to substitute their assess- ment for that of the national authorities or to determine the relevance of the scientific evi- dence adduced by the authorities in support 38. I shall thus consider in turn whether of their revocatory decision. Directive 65/65 or certain rules of Commu- nity law impose obligations of this kind on Member States.

43. That principle, which the Court has con- whether it complies with the principle of pro- sistently confirmed, 15 requires Member States, portionality and, should the need arise, to in the absence of measures harmonising the substitute its own assessment of the facts for procedural conditions governing actions at that made by the Authority. law intended to ensure the protection of the rights which individuals derive from the direct effect of Community law, to ensure that the national procedural conditions introduced to ensure respect for those rights are not '.

44. According to Upjohn, Articles 11 and 2 1 . them, at the conclusion of a precise and of Directive 65/65 are directly effective. The detailed procedure; the fundamental objective first paragraph of Article 11 of Directive pursued by those directives is to ensure that 65/65 thus expressly authorises Member States human health is safeguarded, which requires to revoke marketing licences only '. . . where that decisions be taken rapidly; in performing [the proprietary medicinal product] proves to their functions, national authorities are be harmful in the normal conditions of use, required to carry out complex assessments, or where its therapeutic efficacy is lacking, or and thus to make sensitive choices.

licence. Upjohn therefore contends that, within the context of the judicial review car- 46. Indeed, there can scarcely be any doubt ried out by the competent national courts, that Articles 11 and 21 of Directive 65/65 the task of the national court should be to meet the conditions laid down in the Court's assess whether that decision is factually and case-law 17 for the recognition of direct effect. legally sound, and in particular to determine It follows from the overall system established by Directives 65/65, 75/318 and 75/319, as amended by Directive 83/570, that they estab- 15 — Sec, inter alia. Case 45/76 Comet v Produktschap voor lish precise and detailed rules governing appl-- Siergewassen [1976] ECR 2043, paragraphs 13 and 16; Case 199/82 Amministrazione delle Finanze dello Stato v San Giargio [1983] ECR 3595, paragraph 12; and Case C-208/90 Emmott v Minister for Social Welfare and the Attorney Gen- eral [1991] ECR I-4269. 17 — See, inter alia. Case 8/81 Becker v Finanzamt Münster- 16 — Emmott, cited above, paragraph 16. nnenstadt [1982] ECR 53, paragraph 25.

48. The obligations which those articles 51. It is clear from the wording of numerous impose on Member States reflect perfectly the provisions of the relevant directives cited twofold objective pursued by the above har- above that the national authorities alone are monising directives, which, as already seen, competent in regard to marketing licences for consists in seeking to safeguard public health medicinal products 20 and that, in the exercise and eliminating barriers to the free movement of that function, they are indeed required to of medicinal products, as stated in particular undertake complex assessments 21 on the basis in the first and second recitals in the pre- amble to Directive 65/65. 18 — Sec Clin-Midy and Others and Pierrel and Others, cited above. 19 — In a similar situation, see for instance Norbrook Laborato- ries, cited above, paragraph 90. In another area, see for instance Case C-84/94 United Kingdom v Council [1996] ECR I-5755, paragraph 58. 20 — See, in particular, Articles 3 and 4 of Directive 65/65. 21 — See, in particular, Article 4, second paragraph, point (7) of Directive 65/65, as amended by Directive 75/319, and Article 18 of Directive 75/319, which provide respectively that the national authority must submit the medicinal product for testing by a Sute laboratory or by a laboratory designated 49. The Court has, moreover, already ruled for that purpose in order to ensure that the control methods employed by the manufacturer and described in the particu- that Article 21 of Directive 65/65 is directly lars accompanying the application for a marketing licence comply with the requirements laid down in Directives 65/65, effective and that it must be interpreted as 75/318 and 75/319 and that it must make sure, following an inquiry carried out by its agents, that the particulars sup- meaning that the suspension or revocation of plied pursuant to the requirements of Directive 75/319 are a marketing licence may be decided only on accurate.

55. In this case, however, the assertions of Upjohn are challenged by the respondent in the main proceedings. According to the latter, no less than 15 items of evidence have been 53. Like Upjohn, I take the view that the adduced before the national court. It also principle of effectiveness undoubtedly pro- submits that the comments made by the hibits a national authority from implementing United Kingdom Government and contained national procedural arrangements that limit in the documents before the Court, and on which, according to Upjohn, the parties were unable to set out their views before the national 22 — Sec, in particular, Article 9a of Directive 65/65, as amended by Directive 83/570, which requires the national authority to ensure that the person holding a marketing licence, after the licence has been issued, has taken account, in respect of the control methods provided for in Article 4, point (7), of 23 — Case C-312/93 Peterbroeck v Belgian Sute [1995] Directive 65/65, of technical and scientific progress and ECR I-4599, paragraph 14. introduced any changes that may be required to enable the 24 — Joined Cases C-430/93 and C-431/93 Van Schijndel and Van medicinal product to be checked by means of generally Veen v Stichting Pensioenfonds voor Fysiotherapeuten [1995] accepted scientificmethods. ECR I-4705, paragraph 19.

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UPJOHN v LICENSING AUTHORITY

The third question

58. It follows clearly from the overall system of Community legislation cited above 26 that Member States do not have any discretion as to the penalty for non-compliance with the 61. By its third question, the Court of Appeal is specifically asking the Court to state whether Directive 65/65 must be construed as autho- 25 — See, a contrario, in particular, Case C-7/90 Vande venne and Others [1991] ECR I-4371, paragraph 11. rising a national authority to deliver a deci- 26 — In particular, Articles 4 and 5 of Directive 65/65. sion revoking marketing licences without

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awaiting the definitive opinion of the Com- the Member States concerned must indicate mittee, irrespective of how long it takes the within 60 days what action they intend to Committee to deliver that opinion. take on the Committee's opinion. The wording of that provision thus makes it clear that the Member States are free to take a position other than that of the Committee.

62. It seems to me that the wording of the provisions of Directives 75/319 and 65/65 and the purpose which they serve do not preclude an authority from revoking a marketing licence where the Committee has not delivered its opinion within the period laid down by Direc- 65. This interpretation is perfectly compat- tive 75/319. ible with the purpose and wording of the provisions of Directive 65/65.

I-238

UPJOHN v LICENSING AUTHORITY

Conclusion

68. For those reasons, I propose that the Court reply as follows to the questions submitted to it by the Court of Appeal, London:

(1) Council Directive 65/65/EEC of 26 January 1965 on the approximation of pro- visions laid down by law, regulation or administrative action relating to pro- prietary medicinal products, as amended by Council Directive 83/570/EEC of 26 October 1983, must be construed as not requiring Member States to intro- duce a procedure for judicial review of decisions taken by the competent national authority which would allow the competent national courts to sub- stitute their assessment for that of the national authority or to determine the relevance of the scientific evidence adduced by that authority in support of its decision to revoke a marketing licence for a medicinal product intended for human use.

(2) Directive 65/65 does not require the competent national authority to await the opinion of the Committee for Proprietary Medicinal Products before delivering the above revocatory decision if that Committee has failed to comply with the period laid down by Second Council Directive 75/319/EEC of 20 May 1975 on the approximation of provisions laid down by law, regulation or administra- tive action relating to proprietary medicinal products, as amended by above Directive 83/570.