1 By order of 8 November 1993, received at the Court on 15 November 1993, the Divisional Court of the Queen' s Bench Division of the High Court of Justice (hereinafter "the Divisional Court") referred to the Court for a preliminary ruling under Article 177 of the EC Treaty a question on the interpretation of point (8)(a)(ii) of the second paragraph of Article 4 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, hereinafter "Directive 65/65"), as amended by Council Directive 87/21/EEC of 22 December 1986 (OJ 1987 L 15, p. 36, hereinafter "Directive 87/21"), in order to determine the requirements of Community law applicable to the issue of marketing authorizations for medicinal products where the abridged procedure is used.
2 That question was raised in proceedings between Scotia Pharmaceuticals Ltd (hereinafter "Scotia") and the Medicines Control Agency (hereinafter "MCA") concerning the grant to Norgine Ltd (hereinafter "Norgine"), a competitor of Scotia, of a marketing authorization in respect of a medicinal product under the abridged procedure provided for by Directive 65/65.
3 Since 1965 there has been progressive harmonization at Community level in the field of medicinal products. Directive 65/65, the first to be adopted in that area, concerns the approximation of provisions laid down by law, regulation or administrative action relating to proprietary medicinal products. The first recital in the preamble to this directive states that "the primary purpose of any rules concerning the production and distribution of proprietary medicinal products must be to safeguard public health". The second recital goes on to state that "this objective must be attained by means which will not hinder the development of the pharmaceutical industry or trade in medicinal products within the Community".
4 Article 3 of the directive provides that no medicinal product may be placed on the market unless prior authorization has been issued. Article 4 lays down a list of the documents which must accompany an application for a marketing authorization. Among those documents, point (8) refers to: "Results of: ° physico-chemical, biological or micro-biological tests; ° pharmacological and toxicological tests; ° clinical trials".
5 Point (8) of the second paragraph of Article 4 of Directive 65/65 establishes an abridged procedure in certain cases. The conditions for recourse to that procedure were amended by Directive 87/21.
6 Under point (8)(a)(ii) of the second paragraph of Article 4 of Directive 65/65, as amended, an applicant for a marketing authorization is not required to provide the results of pharmacological and toxicological tests or of clinical trials if he can demonstrate "by detailed references to published scientific literature presented in accordance with the second paragraph of Article 1 of Directive 75/318/EEC that the constituent or constituents of the proprietary medicinal product have a well- established medicinal use, with recognized efficacy and an acceptable level of safety".
7 Article 5 of Directive 65/65 provides that authorization is to be refused if, inter alia, the documents and particulars submitted in support of the application do not comply with Article 4.
8 The first paragraph of Article 1 of Council Directive 75/318/EEC of 20 May 1975 on the approximation of the laws of Member States relating to analytical, pharmacotoxicological and clinical standards and protocols in respect of the testing of proprietary medicinal products (OJ 1975 L 147, p. 1, hereinafter "Directive 75/318") requires Member States to take all appropriate measures to ensure that the particulars and documents which must accompany applications for marketing authorization in respect of a proprietary medicinal product, pursuant to points (3), (4), (6), (7) and (8) of Article 4, second paragraph, of Directive 65/65, are submitted by the persons concerned in accordance with the Annex to Directive 75/318. The second paragraph of that article provides that where an application for authorization is made under the abridged procedure and references to published data are submitted in support of that application, the requirements specified in the first paragraph are to apply in like manner.
9 While the Annex to Directive 75/318 gives details of the particulars and documents which must accompany applications for marketing authorization, 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 (OJ 1975 L 147, p. 3, hereinafter "Directive 75/319") defines the role and duties of the experts who prepare those particulars and documents.
10 Article 1 of Directive 75/319 requires Member States to take all appropriate measures to ensure that the documents and particulars listed in points (7) and (8) of Article 4, second paragraph, of Directive 65/65 are drawn up by experts with the necessary technical or professional qualifications before they are submitted to the competent authorities. According to Article 2(b) and (c) of Directive 75/319, the experts are to describe their observations in accordance with Directive 75/318 and: "where applicable, to state the grounds for using the published references mentioned in point (8)(a) and (b) of Article 4, second paragraph, of Directive 65/65 under the conditions set out in Directive 75/318/EEC".
11 It is apparent from the order for reference that, in the United Kingdom, Scotia is the holder of an authorization granted in 1988 in respect of a product named "Epogam" used in the treatment of atopic eczema. It also holds two authorizations issued in 1990 for "Epogam" in paediatric capsules and for a product called "Efamast", indicated for the relief of mastalgia. Those three authorizations were granted under the normal procedure provided for by Directive 65/65.
12 In 1992 the MCA granted Norgine an authorization to market in the United Kingdom a medicinal product called "Unigam", intended to treat the symptoms of atopic eczema and of cyclical and non-cyclical mastalgia. That application was dealt with under the "abridged" procedure laid down in point (8)(a)(ii) of the second paragraph of Article 4 of Directive 65/65, as amended.
13 All the parties in the main proceedings are at one in stating that the documents submitted in support of Norgine' s application for marketing authorization did not comprise the scientific literature referred to by point (8)(a)(ii) of the second paragraph of Article 4 of Directive 65/65, as amended, concerning each of the tests required by the Annex to Directive 75/318. Nevertheless, according to the MCA, the authority which grants marketing authorization enjoys a discretion enabling it to derogate from the requirements of the directive. It considers that, in granting an authorization for Unigam, it exercised its discretion properly.
14 The Divisional Court considered that the solution of the dispute depended on an interpretation of Community law and referred the following question to the Court of Justice for a preliminary ruling: "In Community law is Directive 65/65/EEC to be interpreted as permitting a national competent authority in the circumstances of a case such as the present to issue an authorization to place a medicinal product on the market pursuant to an application made under Article 4(8)(a)(ii) of Council Directive 65/65/EEC as replaced by Council Directive 87/21/EEC, notwithstanding the fact that the particulars and documents submitted in support of such an application do not contain: (a) detailed references to published scientific literature presented in accordance with each of the requirements of Parts 2 and 3 of the Annex to Directive 75/318/EEC; or (b) experts' reports complying with each of the requirements of Articles 1 and 2 of Directive 75/319/EEC?"
15 It is apparent from the system described above that the relevant directives specify all the scientific and bibliographical information which must be presented in support of an application for authorization, as well as the role of the experts and the circumstances in which the abridged procedure is applicable.
16 Point (8)(a)(ii) of the second paragraph of Article 4 of Directive 65/65, as amended, permits recourse to the abridged procedure if the criteria of established medicinal use, recognized efficacy and an acceptable level of safety are satisfied. However, in that case, the supporting scientific literature must be submitted in accordance with the second paragraph of Article 1 of Directive 75/318.
17 The abridged procedure in no way relaxes the requirements of safety and efficacy which must be met by medicinal products but is merely intended to shorten the period for preparing an application for authorization by freeing the applicant from the obligation to carry out the tests specified in point (8) of the second paragraph of Article 4. However, that obligation is replaced by the obligation to demonstrate by detailed references to published scientific literature that the tests listed in the Annex to Directive 75/318 were carried out previously and showed that the constituent or constituents of the medicinal product satisfied the criteria referred to in Article 4.
18 Nor does recourse to the abridged procedure relax the obligations with which experts must comply by virtue of Articles 1 and 2 of Directive 75/319. Although that procedure substitutes for the requirement to carry out tests the requirement to present, in the form of published references, all the results of the tests performed by other experts, point (b) of the first paragraph of Article 2 of the directive still requires the analyst, pharmacologist and clinician to provide reports containing the information specified by that provision. Moreover, under point (c) of Article 2, first paragraph, the experts must, where applicable, state the grounds for using the published references mentioned in point (8)(a)(ii) of Article 4, second paragraph, of Directive 65/65.
19 The United Kingdom and the Commission both take the view that, in order for the abridged procedure under point (8)(a)(ii) of the second paragraph of Article 4 of Directive 65/65, as amended, to be effective, the competent authority must be allowed a discretion to determine the extent to which an applicant has satisfied the conditions set out in the Annex to Directive 75/318 when supplying references to published literature. They consider that, if that provision were to be more strictly interpreted, the exception relating to published literature would, in practical terms, cease to serve any purpose.
20 That argument must be rejected.
21 In the first place, the competent authority' s power of assessment is limited. It applies to the conclusions of reports drawn up by experts acting in accordance with the legislation in force concerning the feasibility of a test. In that respect the provisions cited above cannot be interpreted as requiring the performance of tests which are in practice impossible to carry out. The competent authority may also use its power of assessment to ascertain whether or not the applicant seeking an authorization, and consequently the expert who prepared the documentation supporting the application, took account of current technical developments and scientific progress and whether or not he or she was satisfied that the scientific publications, on the basis of which the application for authorization was submitted under the abridged procedure, were still up to date.
22 Secondly, as the parties to the main proceedings have noted, recourse to the abridged procedure is exceptional. The documents which have to be submitted in order to make use of that procedure are seldom likely to be found in scientific literature. None the less, that fact cannot justify the competent authorities having a discretion which makes it possible for them to relax the conditions for application of that procedure. Such an interpretation would run counter to the fundamental objective of Directive 65/65, which is to safeguard public health.
23 Thirdly, the second recital in the preamble to Directive 87/21 explains that the main aim of the directive is to "stipulate more precisely the cases in which the results of pharmacological and toxicological tests or clinical trials do not have to be provided with a view to obtaining authorization for a proprietary medicinal product which is essentially similar to an authorized product, while ensuring that innovative firms are not placed at a disadvantage". If, in circumstances such as those in the main proceedings, a discretion were left to national authorities, that objective would be undermined.
24 In the light of all those considerations, the competent authority cannot be considered to have discretion to issue a marketing authorization under the abridged procedure where the scientific literature in the public domain concerning one of the tests required by the Annex to Directive 75/318 is incomplete. In such a case, the conditions laid down in point (8)(a)(ii) of the second paragraph of Article 4 of Directive 65/65, as amended, have not been satisfied and the application for authorization cannot be dealt with under the abridged procedure.
25 On a proper construction, therefore, point (8)(a)(ii) of the second paragraph of Article 4 of Council Directive 65/65, as amended by Directive 87/21, means that a national authority with competence to issue an authorization to place a medicinal product on the domestic market may not issue such authorization where the particulars and documents submitted in support of the application for an authorization do not contain detailed references to published scientific literature presented in accordance with each of the requirements laid down in Parts 2 and 3 of the Annex to Directive 75/318 and where those documents do not comprise experts' reports complying with each of the requirements laid down in Articles 1 and 2 of Directive 75/319.