1 By order of 26 October 1995, received at the Court on 24 March 1997, the Court of Appeal (England and Wales) referred to the Court for a preliminary ruling under Article 177 of the EC Treaty three questions on the interpretation of Council Directive 65/65/EEC of 26 January 1965 on the approximation of provisions laid down by law, regulation or administrative action relating to proprietary medicinal products (OJ, English Special Edition 1965-1966, p. 20).
2 Those questions were raised in proceedings brought by Upjohn Ltd (`Upjohn') against the Licensing Authority established by the Medicines Act 1968 and the Ministers collectively exercising authority as the Licensing Authority, concerning the decision of that authority to revoke with immediate effect all authorisations to market a medicinal product known as `Triazolam', which is also registered by the applicant in the main proceedings under the brand name `Halcion'. The Community legislation
3 Article 11 of Directive 65/65, in the version thereof resulting from Council Directive 83/570/EEC of 26 October 1983 amending Directives 65/65/EEC, 75/318/EEC and 75/319/EEC (OJ 1983 L 332, p. 1), provides: `The competent authorities of the Member States shall suspend or revoke an authorisation to place a proprietary medicinal product on the market where that product proves to be harmful in the normal conditions of use, or where its therapeutic efficacy is lacking, or where its qualitative and quantitative composition is not as declared. Therapeutic efficacy is lacking when it is established that therapeutic results cannot be obtained with the proprietary product. An authorisation shall also be suspended or revoked where the particulars supporting the application as provided for in Articles 4 and 4a are incorrect or have not been amended in accordance with Article 9a, or when the controls referred to in Article 8 of this Directive or in Article 27 of Second Council Directive 75/319/EEC of 20 May 1975 on the approximation of provisions laid down by law, regulation or administrative action relating to proprietary medicinal products have not been carried out.'
4 Under the first paragraph of Article 12 of Directive 65/65, all decisions taken pursuant to, inter alia, Article 11 are to state in detail the reasons on which they are based. Such a decision is to be notified to the party concerned, who must at the same time be informed of the remedies available to him under the laws in force and of the time-limit allowed for the exercise of such remedies.
5 Article 21 of Directive 65/65 provides that a marketing authorisation may not be refused, suspended or revoked except on the grounds set out in that directive.
6 Article 8 of Directive 75/319/EEC (OJ 1975 L 147, p. 13), as amended by Directive 83/570, provides: `In order to facilitate the adoption of a common position by the Member States with regard to decisions on the issuing of marketing authorisations and to promote thereby the free movement of proprietary medicinal products, a Committee for Proprietary Medicinal Products ... is hereby set up. The Committee shall consist of representatives of the Member States and of the Commission ... [and shall examine questions] at the request of a Member State or the Commission ... '.
7 Under the first and second paragraphs of Article 11 of Directive 75/319, as amended by Directive 83/570, where one or more Member States have suspended or revoked a marketing authorisation while one or more other Member States have not done so, one of the Member States concerned or the Commission may refer the matter to the Committee for Proprietary Medicinal Products (hereinafter `the CPMP') for application of the procedure referred to in Article 14 of that directive.
8 The first subparagraph of Article 14(1) of Directive 75/319, as amended by Directive 83/570, provides that, when reference is made to the procedure described in that article, the CPMP is to consider the matter concerned and issue a reasoned opinion within 60 days of the date on which the matter was referred to it. The first subparagraph of Article 14(2) states that the CPMP's opinion is to concern, inter alia, the grounds on which the marketing authorisation has been suspended or withdrawn in the cases described in Article 11.
9 The second subparagraph of Article 14(2) requires the CPMP immediately to inform the Member State(s) concerned and the person responsible for placing the product on the market of its opinion or of those of its members in the case of divergent opinions. Lastly, Article 14(3) provides that the Member State(s) concerned are to decide what action to take on the CPMP's opinion within 60 days of receipt of the information referred to in the second subparagraph of Article 14(2). The national legislation
10 Under the Medicines Act 1968, which is the basic statute governing marketing authorisations for proprietary medicinal products in the United Kingdom, the competent authority for the issue of marketing authorisations is the Licensing Authority, which delegates its regulatory functions to an executive agency, the Medicines Control Agency (`the MCA').
11 The Committee for the Safety of Medicines (`the CSM') must be consulted by the Licensing Authority in proceedings relating to the suspension, revocation or variation of marketing authorisations.
12 The Medicines Commission is also required to advise the Licensing Authority on authorisations and certificates relating to proprietary medicinal products.
13 The national legislation in force provides that, where the Licensing Authority proposes to revoke a marketing authorisation, an administrative procedure is to be conducted in the course of which the holder of the authorisation may make representations and, in particular, may produce any relevant documents and procure the assistance of experts of its choice with a view to showing that the proprietary medicinal product under examination by the administrative authority possesses the characteristics required by Directive 65/65 for its authorisation.
14 Under section 107 of the Medicines Act, any person concerned by, in particular, a decision revoking a marketing authorisation may, within three months of the date on which notice of the decision is served on him, make an application to the High Court contesting the validity of that decision on the grounds: (a) that it is not within the powers of that Act, or (b) that any of the requirements of that Act or of any regulations made under that Act which are applicable to the matter to which the decision relates have not been complied with. The dispute in the main proceedings
15 Triazolam, which is also marketed under Upjohn's brand name Halcion, is a benzodiazepine-based prescription drug for the treatment of insomnia. Triazolam was first authorised in the United Kingdom in September 1978 for tablets in dosages of 0.25 mg and 0.125 mg.
16 In July 1991 the MCA learned from a newspaper article that a middle-aged woman had killed her mother while under the influence of Triazolam. Having sought the views of the CSM, which provisionally concluded that the marketing authorisations should be revoked, the MCA informed Upjohn on 2 October 1991 that the Licensing Authority had decided to suspend the marketing authorisations for that product for three months. That suspension was renewed at three-monthly intervals until 9 June 1993, the date on which the marketing authorisations were revoked.
17 In parallel with the national procedure and in accordance with the second paragraph of Article 11 of Directive 75/319, as amended, the matter was referred to the CPMP in October 1991 by the French Republic and the Kingdom of the Netherlands. On 11 December 1991 the CPMP issued its opinion, which was against a total revocation of the marketing authorisations and requested the ad hoc rapporteurs' group appointed by the CPMP to supplement the work already done by assessing the relative risk-benefit ratios of all short-acting hypnotics, including Triazolam.
18 However, despite that opinion, and that of the Medicines Commission recommending revocation only of the marketing authorisations relating to doses of 0.25 mg, the MCA informed Upjohn on 17 July 1992 that the Licensing Authority was proposing the definitive revocation of all marketing authorisations in respect of Triazolam. It stated that the Licensing Authority had taken into account the opinion of the CPMP of 11 December 1991.
19 The MCA further informed Upjohn that, inasmuch as the Licensing Authority did not share the opinion of the Medicines Commission, Upjohn had the right to be heard by the `Person Appointed' or `Persons Appointed' by the Licensing Authority. Upjohn availed itself of that right and was heard by the Persons Appointed. Their report concluded that the benefits of Triazolam in doses of 0.25 mg and 0.125 mg outweighed the risks.
20 As regards the procedure before the CPMP referred to in paragraph 17 of this judgment, the draft summaries of product characteristics prepared by the ad hoc rapporteurs' group in respect of all short-acting hypnotics, including Triazolam, were considered by that committee on 11 and 12 May 1993. The draft summary of product characteristics allowed Triazolam to be prescribed in doses of 0.25 mg and 0.125 mg for adults and 0.125 mg for the elderly. The CPMP considered favourably the recommendations of the ad hoc group. The draft summaries of product characteristics were then communicated to the Member States and to the holders of the marketing authorisations concerned. Comments were invited by 1 July 1993 for consideration by the CPMP at its meeting on 13 and 14 July 1993.
21 However, on 9 June 1993 the Licensing Authority communicated to Upjohn its decision revoking, with immediate effect, all marketing authorisations relating to Triazolam. It provided a detailed statement of reasons for that decision and for its rejection of the conclusions of the Persons Appointed.
22 On 15 September 1993 the CPMP adopted the report of the ad hoc rapporteurs' group, which concluded, in particular, that Triazolam should continue to be sold.
23 Meanwhile, on 31 August 1993 Upjohn brought proceedings before the High Court to have the Licensing Authority's decision of 9 June 1993 quashed. It maintained in those proceedings that it was necessary, prior to any examination of the substance of the case, to request the Court of Justice to provide guidance on the way in which the national courts should proceed in examining the case. The High Court held that there was no need to make a reference to the Court of Justice.
24 Upjohn therefore appealed against that decision to the Court of Appeal, which decided to stay proceedings and referred the following questions to the Court of Justice for a preliminary ruling: `1. On the true construction of Council Directive 65/65/EEC as amended and in the light of Community law generally, is it the duty of a national court when ruling upon the compatibility with the aforesaid Community law of a decision of a licensing authority of a Member State to revoke a licence held by the manufacturer of a medicine product to decide whether or not the said decision was the correct decision as opposed to a decision which the licensing authority could reasonably have reached on the material before it? 2. If the answer to Question 1 is that the national court has to decide whether the decision of the competent authority was the correct decision does Community law require it to answer that question solely on the basis of the material before the competent authority or is it obliged to look at any relevant material coming to light after the decision? 3. Was it lawful for the Licensing Authority to revoke the licence when the Committee for Proprietary Medicinal Products (CPMP) was known to the Licensing Authority to be soon to produce an opinion as to continuance of the licence?'
25 It is apparent from the proceedings before the High Court and the Court of Appeal that, according to Upjohn, Directive 65/65 and, more generally, Community law require the Member States to establish a procedure for judicial review of decisions taken by the national authorities responsible for marketing authorisations, empowering the national courts to verify, on the basis of a fresh, comprehensive assessment of the issues of fact and of law, whether the decision taken was correct. In particular, the national court seised of the application for an order quashing the decision revoking the marketing authorisations relating to Triazolam should be empowered to decide whether, having regard to the scientific evidence on which it is based, that decision is correct.
26 By contrast, the Licensing Authority has maintained that, according to Directive 65/65, there can be only one national authority competent to take decisions concerning the production and marketing of proprietary medicinal products and, in particular, decisions revoking marketing authorisations. In the United Kingdom, the competent authority in such matters is precisely the Licensing Authority. Thus, the national court seised of the application contesting the decision revoking the marketing authorisations in respect of Triazolam is not empowered to take the place of the Licensing Authority; it may rule only on the question whether the contested decision is vitiated by a defect requiring it to be quashed. The first question
27 By its first question, the national court asks, in essence, whether Directive 65/65 and, more generally, Community law require the Member States to establish a procedure for judicial review of national decisions revoking marketing authorisations for proprietary medicinal products, whereby the national courts and tribunals having jurisdiction are empowered to substitute their assessment of the facts, and, in particular, of the scientific evidence relied on in support of the revocation decision, for the assessment made by the national authorities competent to revoke such authorisations.
28 It is clear that, within the framework of rules governing proprietary medicinal products laid down by the relevant Community legislation, only Article 12 of Directive 65/65 refers to the remedies available against decisions taken pursuant to Article 11 of the directive, that is to say, decisions suspending or revoking marketing authorisations for proprietary medicinal products. As indicated in paragraph 4 of this judgment, the first paragraph of Article 12 merely requires the Member States to provide for such decisions to be open to challenge by way of legal proceedings.
29 It is apparent, therefore, that Article 12 does not lay down detailed rules for the exercise of the right of recourse; it leaves to the Member States the task of organising their own systems of judicial review of decisions refusing, suspending or revoking marketing authorisations for proprietary medicinal products.
30 Upjohn maintains that, since Article 11 of Directive 65/65, as amended, is directly applicable, the national court must be able to review fully the action taken by the administrative authority. Otherwise, the rights enjoyed by Upjohn by virtue of the direct effect of that provision would not be effectively safeguarded.
31 In that connection, it is apparent from the Court's case-law that, in so far as Article 11 of Directive 65/65 lays down the criteria for revocation of a marketing authorisation, it has direct effect, in the same way as Article 21, which provides that a marketing authorisation may be revoked only on the public health grounds expressly mentioned in the directive (Case 301/82 Clin-Midy and Others v Belgium [1984] ECR 251, paragraphs 4 and 10).
32 It is settled case-law that in the absence of Community rules governing the matter it is for the domestic legal system of each Member State to designate the courts and tribunals having jurisdiction and to lay down the detailed procedural rules governing actions for safeguarding rights which individuals derive from Community law, provided, however, that such rules are not less favourable than those governing similar domestic actions (the principle of equivalence) and do not render virtually impossible or excessively difficult the exercise of rights conferred by Community law (the principle of effectiveness) (see, in particular, Case C-312/93 Peterbroeck v Belgian State [1995] ECR I-4599, paragraph 12, and paragraph 18 of the judgment in Case C-326/96 Levez [1998] ECR I-7835).
33 As regards decisions revoking marketing authorisations taken by the competent national authorities following complex assessments in the medico-pharmacological field, it does not appear that the only appropriate means of preventing the exercise of rights conferred by Community law from being rendered virtually impossible or excessively difficult would be a procedure for judicial review of national decisions revoking marketing authorisations, empowering the competent national courts and tribunals to substitute their assessment of the facts and, in particular, of the scientific evidence relied on in support of the revocation decision for the assessment made by the national authorities competent to revoke such authorisations.
34 According to the Court's case-law, where a Community authority is called upon, in the performance of its duties, to make complex assessments, it enjoys a wide measure of discretion, the exercise of which is subject to a limited judicial review in the course of which the Community judicature may not substitute its assessment of the facts for the assessment made by the authority concerned. Thus, in such cases, the Community judicature must restrict itself to examining the accuracy of the findings of fact and law made by the authority concerned and to verifying, in particular, that the action taken by that authority is not vitiated by a manifest error or a misuse of powers and that it did not clearly exceed the bounds of its discretion (see, in particular, Joined Cases 56/64 and 58/64 Consten and Grundig v Commission [1966] ECR 299, Case 55/75 Balkan-Import Export v Hauptzollamt Berlin-Packhof [1976] ECR 19, paragraph 8, Case 9/82 hrgaard and Delvaux v Commission [1983] ECR 2379, paragraph 14, Case C-225/91 Matra v Commission [1993] ECR I-3203, paragraphs 24 and 25, and Case C-157/96 National Farmers' Union and Others [1998] ECR I-2211, paragraph 39).
35 Consequently, Community law does not require the Member States to establish a procedure for judicial review of national decisions revoking marketing authorisations, taken pursuant to Directive 65/65 and in the exercise of complex assessments, which involves a more extensive review than that carried out by the Court in similar cases.
36 Nevertheless, any national procedure for judicial review of decisions of national authorities revoking marketing authorisations must enable the court or tribunal seised of an application for annulment of such a decision effectively to apply the relevant principles and rules of Community law when reviewing its legality.
37 In the light of the foregoing, the answer to the first question must be that Directive 65/65 and, more generally, Community law do not require the Member States to establish a procedure for judicial review of national decisions revoking authorisations to market proprietary medicinal products, empowering the competent national courts and tribunals to substitute their assessment of the facts and, in particular, of the scientific evidence relied on in support of the revocation decision for the assessment made by the national authorities competent to revoke such authorisations. The second question
38 By its second question, the Court of Appeal asks, in essence, whether Community law requires a national court which is seised of an application for annulment of a decision revoking a marketing authorisation for a particular proprietary medicinal product to take into account, when determining that application, any relevant scientific material coming to light after the adoption of that decision.
39 A system of judicial review whereby the national courts are to determine applications for annulment of decisions revoking marketing authorisations without taking into account relevant scientific material coming to light after the adoption of the contested decision is not such as to render virtually impossible or excessively difficult the exercise of the rights conferred by the directive.
40 As the United Kingdom Government has argued, in the event of new material coming to light following the adoption of a decision revoking a marketing authorisation, the person concerned will still be able to make a fresh application for a marketing authorisation. It will then be for the competent administrative authority to assess, in the light of all the information at its disposal, whether the criteria for the grant of a fresh marketing authorisation are fulfilled.
41 In the present case, this represents an acceptable solution, having regard, first, to the fact that the scientific criteria, especially those concerning the harmful nature of a proprietary medicinal product in respect of which the marketing authorisation has been revoked, are liable to change in the course of time and, second, to the fact that Directive 65/65 does not require the Member States to establish a procedure for judicial review of national decisions revoking marketing authorisations for proprietary medicinal products, empowering the competent national courts and tribunals to substitute their assessment of the facts and, in particular, of the scientific evidence relied on in support of the revocation decision for the assessment made by the national authorities competent to revoke such authorisations.
42 It follows that the answer to the second question must be that Community law does not require a national court or tribunal which is seised of an application for annulment of a decision revoking a marketing authorisation for a particular proprietary medicinal product to take into account, when determining that application, any relevant scientific material coming to light after the adoption of that decision. The third question
43 By its third question, the national court asks, in essence, whether, in the event that the matter has been referred by various Member States to the CPMP following the adoption by the competent national authority of a decision revoking a marketing authorisation and the time-limit for the issue by the CPMP of its opinion has expired, Directives 65/65 and 75/319, as amended by Directive 83/570, preclude that authority from deciding to revoke the marketing authorisation in question without awaiting the opinion of the CPMP.
44 According to the first and second paragraphs of Article 11 of Directive 75/319, as amended by Directive 83/570, where one or more Member States have suspended a marketing authorisation while one or more other Member States have not done so, one of the Member States concerned may refer the matter to the CPMP for application of the procedure referred to in Article 14 of that directive.
45 Article 14 of Directive 75/319 provides that, when reference is made to the procedure described in that article, the CPMP is to consider the matter and issue a reasoned opinion within 60 days of the date on which the matter was referred to it. The CPMP must immediately inform the Member State(s) concerned and the person responsible for placing the product on the market of its opinion or of those of its members in the case of divergent opinions. The Member State(s) concerned must communicate their decision concerning the action to be taken on the CPMP's opinion within 60 days of receipt of the information contained therein.
46 It is unnecessary to rule on the question whether, under the abovementioned provisions, a national authority is empowered to order the revocation of a marketing authorisation within the period of 60 days following the reference of the matter to the CPMP, since it is clear that such an authority is in no way precluded from revoking a marketing authorisation where the CPMP has not produced its opinion within that time-limit.
47 As the Advocate General has stated in points 63 and 64 of his Opinion, the opinion of the CPMP is in no way binding. Moreover, since the issue is one of public health, Article 14 cannot be construed as requiring Member States to await the CPMP's opinion, even after the period of 60 days allowed for its production has expired, before deciding to withdraw a medicinal product that may prove to be harmful to public health, the protection of which constitutes the primary objective of Directive 65/65.
48 Consequently, the answer to the third question must be that Directives 65/65 and 75/319, as amended by Directive 83/570, are to be construed as meaning that, where the matter has been referred by various Member States to the CPMP following the adoption by the competent national authority of a decision revoking a marketing authorisation and the time-limit for the issue by the CPMP of its opinion has expired, those directives do not preclude that authority from deciding to revoke the marketing authorisation in question without awaiting the opinion of the CPMP.