61995CC0127_EN
Opinion of the Advocate-General
Opinion of the Advocate-General
1 The Court of Appeal in Northern Ireland (`the Court of Appeal') requests an interpretation and a determination of the validity of a number of provisions in Council Directives 81/851/EEC (1) and 81/852/EEC. (2)
More particularly, the reference concerns provisions relating to the information which the national authority responsible for the grant, suspension and withdrawal of marketing authorisations for veterinary medicinal products (hereinafter `the competent authority') may properly require concerning the manufacturer, the manufacturing process and the methods for monitoring the composition of a non-active ingredient (or `substance') which enters into the composition of one of the active ingredients necessary for the manufacture of a veterinary medicinal product for which marketing authorisation is sought.
The Court is also requested to rule on the conditions under which a Member State may become liable for a breach of Community law.
Factual and procedural background
2 Norbrook Laboratories Ltd (hereinafter `Norbrook' or `the plaintiff') is an English limited-liability company which, from its manufacturing premises at Newry, Northern Ireland, manufactures and distributes in 45 countries an injectable product known as `Pen & Strep'.
3 This veterinary medicinal product is an antibiotic frequently used for the treatment of bacterial infections in cattle, pigs and sheep.
It contains two main active ingredients, procaine penicillin (`PP') and dihydrostreptomycin sulphate (`DHS').
4 DHS is itself manufactured from streptomycin sulphate (hereinafter `SS', `the disputed product' or `the disputed substance'), which is not an active ingredient.
Those two substances have been very widely used in products intended for the treatment of animals, and are generally considered to be effective and low in side-effects.
5 Pen & Strep was first marketed in Ireland and the United Kingdom in 1968, the Netherlands in 1970, Belgium and France in 1981 and Denmark in 1989.
6 On 28 August 1987, following the entry into force of Community directives concerning marketing authorisation for veterinary medicinal products, (3) Norbrook filed an application for a `reviewed' marketing authorisation (4) for `Pen & Strep' with the competent authority, the Ministry of Agriculture, Fisheries and Food (hereinafter `the MAFF' or `the defendant'), which delegates certain implementing powers to the Veterinary Medicines Directorate (`the VMD').
It stated in its application that the medicinal product in question would be manufactured from DHS supplied by Rhône Poulenc Industrie of France.
7 On 9 March 1990, the plaintiff requested authorisation to market Pen & Strep manufactured on the basis of DHS produced for many years by Norbrook itself, and on the basis of SS purchased from approximately 20 suppliers.
8 Following receipt of those new data, the VMD asked Norbrook to communicate to it certain information as to the identity and location of those suppliers of SS and as to the manufacturing and control methods of that product. Faced with silence from Norbrook, the VMD notified the company on 13 May 1991 that the authorisation previously granted for the product Pen & Strep had expired with effect from 12 March 1991 and that the `reviewed' authorisation which replaced it permitted the company to use only DHS from the source indicated in its application of 28 August 1987.
9 As to the reasons why it cannot comply with those requests, Norbrook explains: `This information is frequently not available to Norbrook when purchasing through intermediaries on the spot market.
Even in those instances where the identity of the SS manufacturer could be obtained by Norbrook, many manufacturers, particularly those outside Europe, would be unwilling to disclose confidential material as to their manufacturing and control processes to government agencies of a "foreign" country.' (5)
10 That request for further information from the VMD lies at the root of the dispute which brought Norbrook to the High Court of Justice in Northern Ireland, Queen's Bench Division, whose judgment was set aside on appeal by the Court of Appeal.
Taking the view that an interpretation and a determination of the validity of the relevant Community provisions were necessary in order to resolve the dispute, the Court of Appeal has referred the following seven questions to this Court for a preliminary ruling:
`1. Are Council Directives 81/851/EEC and 81/852/EEC (and in particular Articles 5, 8, 9, 11, 29 to 31, 35, 40 and 41 of Directive 81/851/EEC and Part 1 of the Annex to Directive 81/852/EEC in the form in which they existed prior to any amendment) to be interpreted as permitting the competent authority of a Member State, in circumstances such as those hereinbefore described:
(a) to require an applicant for marketing authorisation in respect of a veterinary medicinal product ("the Product") to identify or to arrange to be identified to the competent authority the names and addresses of any and all manufacturers of a particular substance ("the Substance") from whom the applicant intends to purchase quantities of the Substance for use in the manufacture by the applicant of one of the active ingredients ("the Active Ingredient") of the Product, and to supply or arrange to be supplied to the competent authority details of the site(s) where the Substance would be manufactured and of the manufacturing processes and control testing procedures used by the manufacturer of the Substance;
(b) to require an applicant for a marketing authorisation to submit to the competent authority for approval the results of such control tests as are required to be carried out upon each batch of the Substance purchased by the applicant, and not to release any batch of the Product until such approval has been given in respect of the relevant batch of the Substance;
(c) to require the applicant (whether by specific licence conditions or by withholding grant of a marketing authorisation or otherwise) either to comply with one or both of the above requirements or to market the Product only where it has been prepared using supplies of the Active Ingredient purchased from a specified third party rather than manufactured by the applicant itself;
(d) to suspend the time-limits for a grant of a marketing authorisation laid down by Article 8 of Directive 81/851/EEC until the applicant has agreed to supply the information referred to in (a) above.
2. Is it material to the answers in Questions 1(a) to (d) above whether the process of manufacture of the Product is continuous or other than continuous, and, if so, what would be the effect on the answers to those questions?
3. Would it be material to the answers to Questions 1(a) to (d) above if it were not reasonably possible for an applicant to obtain any of the information referred to in Question 1(a) and, if so, what would be the effect on the answers to those questions?
4. (a) If the requests for further information and the other requirements described in Question 1 above, or any of them, are prima facie permissible under Council Directive 81/851/EEC and 81/852/EEC, must such requests and requirements comply with the Community law principle of proportionality?
(b) If the answer to (a) is affirmative, are those principles to be applied in this case by the national court or by the Court of Justice?
(c) (i)
If they are to be applied by the Court of Justice, do the said requests and requirements or any of them infringe the principles of proportionality?
(ii)
If they are to be applied by the national court, by reference to what criteria and considerations must the proportionality of the requests and requirements be assessed?
5. Are Articles 30 to 36 of the EC Treaty to be interpreted as prohibiting requests and requirements such as those described above, or any of them?
6. (a) Is Article 40 of Council Directive 81/851/EEC to be interpreted as applying to the requests and requirements described above?
(b) If so, in what circumstances and by reference to what criteria are the reasons for the imposition of such requests and requirements to be treated as inadequate for the purposes of Article 40, and were such requests and requirements adequately reasoned in the present case?
7. (a) Is a Member State liable as a matter of Community law to compensate an undertaking for damages for loss which it has suffered as a consequence of the imposition of requests and requirements such as those described above which
(i)
are incompatible with the provisions of Council Directives 81/851 and/or 81/852;
(ii)
infringe the principles of proportionality;
(iii)
are prohibited by Articles 30 to 36 of the Treaty;
(iv)
are insufficiently reasoned within the meaning of Article 40 of Directive 81/851?
(b) If the answer to Question 7(a)(i), (ii), (iii) and (iv) or any of them is in the affirmative, under what conditions does such liability arise?'
11 The second and third questions amplify the first, which requests the Court to determine whether Directives 81/851 and 81/852 are to be interpreted as authorising a competent authority to require an applicant for authorisation to market a veterinary medicinal product (hereinafter `the applicant for marketing authorisation' or `the person responsible for marketing') to provide, first, information as to the manufacturer and manufacturing process of a non-active ingredient entering into the composition of one of the active ingredients necessary to manufacture that veterinary medicinal product, and, secondly, information as to the operations for monitoring the composition of the substance itself.
The sixth question concerns the interpretation of Article 40 of Directive 81/851.
12 If the first question is answered in the affirmative, the Court is requested, in the fourth and fifth questions, to determine the validity of those stipulations in the light of the principle of proportionality and of Articles 30 to 36 of the Treaty.
13 If the first question is answered in the negative, the Court is asked finally, in the seventh question, what the necessary conditions are for a Member State to incur liability for a breach of Community law.
Legislative background
The Community legislation
14 Within the Union, harmonisation of the conditions for granting, suspending and withdrawing marketing authorisation for proprietary medicinal products for human use was carried out in 1965 by Council Directive 65/65/EEC, (6)
which, although amended on a number of occasions, remains applicable.
The Court has been called upon to interpret its provisions many times. (7)
15 In relation to veterinary medicinal products, that harmonisation did not take place until 1981, with the two directives cited above, which have since been significantly amended to take account of scientific progress. (8)
16 Like Directive 65/65, Directive 81/851 is presented as `a stage in the achievement of the aim of freedom of movement of veterinary medicinal products'. (9)
This Court has very rarely been called upon to interpret Directives 81/851 and 81/852, (10) unlike the directives concerning medicinal products for human use.
17 The national court expressly limits its reference to the rules laid down by the original versions of Directives 81/851 and 81/852.
The relevant provisions of Directive 81/851
18 This directive is intended to harmonise the laws of the Member States concerning veterinary medicinal products and, in particular, the conditions for issuing, suspending and withdrawing marketing authorisations.
The directive pursues two aims, namely the safeguarding of public health and free movement of medicinal products.
Thus, in the first recital in its preamble, it states that the primary purpose of any rules for the production and distribution of veterinary medicinal products must be the safeguarding of public health.
The 11th recital states that the directive is only one stage in the achievement of the aim of freedom of movement of veterinary medicinal products, and that new measures will prove necessary, in the light of experience gained, for the removal of the remaining barriers to freedom of movement.
19 Article 4(1) of the directive provides that:
`No veterinary medicinal product may be marketed in a Member State unless authorisation has previously been issued by the competent authority in that Member State.'
20 Article 5(2) of Directive 81/851 lists 13 particulars or documents which must be submitted in support of an application for marketing authorisation.
21 Under the first paragraph of Article 8, the duration of the procedure for granting marketing authorisation must not exceed 120 days as from the date of submission of the application.
22 Having stipulated that the dossier submitted in support of such an application must be drawn up by experts having the necessary technical or professional qualifications, (11) Directive 81/851 explains the role of those experts. (12)
23 Article 9 lays down the procedure for examining applications for marketing authorisation.
24 Article 11 provides that marketing authorisation must be refused if the documents and particulars submitted in support of the application do not comply with the provisions of Articles 5, 6 and 7 cited above, and if the veterinary medicinal product does not ensure the protection of public health, consumers, or animal health.
It must thus comply with the three criteria commonly defined in this area:
quality, harmlessness and therapeutic effectiveness.
25 Article 40 lays down rules concerning the stating of reasons for, and notification of, certain decisions taken under the directive.
26 Article 41 further provides that no decision to withhold, withdraw or suspend marketing authorisation may be taken on grounds other than those set out in the directive.
The relevant provisions of Directive 81/852
27 The aim of Directive 81/852 is to approximate the laws of the Member States on control methods for veterinary medicinal products by requiring the competent authorities to examine applications for marketing authorisation in accordance with the protocols described in the directive. In the first recital in its preamble, the directive states that its aim is to implement the principles laid down in Directive 81/851.
Thus the third recital states that: `... standards and protocols for the performance of tests and trials on veterinary medicinal products are an effective means of control of these products and, hence, of protecting public health and can facilitate the movement of these products by laying down uniform rules applicable to tests and trials and the compilation of dossiers'. (13)
28 The directive lays down the principle of compliance with minimum standards in relation to control methods for veterinary medicinal products:
`Member States shall take all appropriate measures to ensure that the particulars and documents which shall accompany applications for authorisation to place a veterinary medicinal product on the market, pursuant to points 3, 4, 6, 8, 9 and 10 of the second paragraph of Article 5 of Directive 81/851/EEC, are submitted by the persons concerned in accordance with the Annex to this Directive.' (14)
29 That annex contains three parts (otherwise referred to as `protocols').
The first concerns analytical tests of veterinary medicinal products, (15) the second tests of toxicity, pharmacodynamics (16) and pharmacokinetics, (17) the third clinical trials. (18)
30 The relevant provisions for answering the questions referred appear in the first protocol.
It is divided into six numbered parts from A to F, concerning respectively: qualitative and quantitative particulars of the constituents (A), description of the method of preparation (B), control of starting materials (C), control tests during manufacture (D), control tests on the finished product (E), and, finally, stability tests (F).
31 I shall return to the actual stipulations of Directives 81/851 and 81/852 in the arguments I shall advance in reply to the questions. (19)
The national legislation
32 In the United Kingdom, Directives 81/851 and 81/852 are regarded as having been implemented by the Medicines Act 1968 (`the 1968 Act') as amended, and by subordinate legislation.
33 Marketing authorisations are required for all veterinary medicinal products, (20) and applications for the grant of such authorisation must comply with specific criteria and a specific procedure. (21)
34 Various information is required (22) in the case of a medicinal product - whether for human or veterinary use - manufactured or assembled in the United Kingdom.
35 Marketing authorisations are normally valid for five years, unless a shorter duration is specified.
36 When Directives 81/851 and 81/852 entered into force, marketing authorisations previously granted for veterinary medicinal products were re-examined under the `review' procedure laid down by Directive 81/851, the aim of which is to ensure that products previously authorised comply with Community rules.
37 It is in the context of that procedure for `reviewed' marketing authorisation that the dispute between Norbrook and the VMD has arisen. (23)
Replies to the questions referred for a preliminary ruling concerning the interpretation of Directives 81/851 and 81/852
Question 1
38 Question 1 essentially concerns two points:
the requirements imposed by Directives 81/851 and 81/852 concerning the grant of marketing authorisation and those concerning the conditions for suspension and refusal of such authorisation for a veterinary medicinal product.
The requirements imposed by Directives 81/851 and 81/852 concerning the grant of marketing authorisation
39 Question 1(a) asks the Court to determine whether, in circumstances such as those described in the order for reference, Directives 81/851 and 81/852 are to be interpreted as authorising a competent authority to require the person responsible for marketing to provide information concerning the manufacturer - namely the name(s) and address(es) of the manufacturer(s) and details of the site(s) where a substance is manufactured -, the manufacturing process and the control methods used by the manufacturer of a substance such as SS.
40 Articles 5, 6, 7 and point 1 of the first paragraph of Article 9 of Directive 81/851 lay down the obligations with which Member States must comply before granting marketing authorisation for a veterinary medicinal product.
The `standards and protocols' directive specifies in greater detail the control methods to be applied to a veterinary medicinal product for which marketing authorisation has been applied for.
41 As regards the requirements laid down by the Community harmonisation directives on marketing authorisation for human medicines, (24) the Court held in Case C-440/93 R v Licensing Authority of the Department of Health, ex parte Scotia Pharmaceuticals [1995] ECR I-2851 that the competent authorities are under a strict duty to comply with them:
`... 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 authorisation, 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 authorisation was submitted under the abridged procedure, were still up to date.' (25)
42 Since the wording of the various provisions in the harmonisation directives concerning marketing authorisation for both human and animal medicines is similar, (26) as are the aims pursued, (27) the above case-law must, in my view, be transposed to the present case.
43 Therefore, in accordance with the judgment in Scotia Pharmaceuticals, all the numerous and precise requirements in Directives 81/851 and 81/852 must be complied with by the competent authority.
44 The degree of stringency in relation to those particulars depends on the nature of the product in question (excipient, active ingredient or constituent of the pharmaceutical form (28)).
It is therefore important to determine the nature of SS, which is the substance in question in this case.
45 In the summary of the factual background to the main proceedings (29) it is explained that SS is not an active ingredient, but that it goes into the manufacture of the active ingredient, DHS, of which it is the sole ingredient, and that it is manufactured from the disputed product. (30)
46 At the hearing, the Commission's expert stated that the disputed product should be regarded as a `starting material' within the meaning of Directive 92/18, which provides that:
`Where source materials such as micro-organisms, tissues of either plant or animal origin, cells or fluids (including blood) of human or animal origin or biotechnical cell constructs are used in the manufacture of veterinary medicinal products, the origin and history of starting materials shall be described and documented.
The description of the starting material shall include the manufacturing strategy, purification/inactivation procedures with their validation and all in-process control procedures designed to ensure the quality, safety and batch to batch consistency of the finished product.' (31)
According to that expert, that `source material' is to be assimilated to a `starting material' within the meaning of Directives 81/851 and 81/852.
The United Kingdom shares that opinion. (32)
47 Norbrook disputes the results of the scientific analysis undertaken by the Commission and United Kingdom experts and does not agree that SS should be regarded as a starting material.
It refers to the results of an expert study carried out at its request, and argues that Directive 92/18 did not come into force until after the company's dispute with the MAFF.
48 I do not think that the latter argument is capable of preventing the competent authority from requiring production of new tests in support of an application for marketing authorisation, for two main reasons.
49 First, the Community legislature has itself indicated that, because of the specificity of the subject-matter of these directives, the tests provided for in Directive 81/852 may be replaced by others, which may be more relevant in the light of scientific progress. (33)
Thus, the first paragraph of Article 14 of Directive 81/851 provides:
`The person responsible for marketing shall modify the control test method provided for in point 9 of Article 5 (34) in accordance with technological and scientific progress, if such modification is needed to enable the veterinary medicinal product to be controlled with a greater degree of security.'
50 To hold otherwise would risk neutralising the effectiveness of such legislation.
Since the main aim of this Community legislation is to safeguard public health, where new scientific data show that more efficient tests are advisable in order to ensure the safety, effectiveness and quality of the medicinal product, those tests must be carried out.
51 Secondly, the Court has already confirmed that interpretation in the Scotia Pharmaceuticals judgment, cited above, by stating that:
`The competent authority may ... use its power of assessment to ascertain whether or not the applicant seeking an authorisation, 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 authorisation was submitted under the abridged procedure, were still up to date.' (35)
52 However, it is not appropriate to assess the argument based on the expert study carried out at the request of Norbrook.
Under the first paragraph of Article 14 of Directive 81/851, only the national court, taking account of the particular characteristics of SS and current technological and scientific progress, has jurisdiction to assess whether the tests prescribed for starting materials under Directives 81/851 and 81/852 must be carried out on SS.
53 In the remainder of my argument, in order to avoid the trap of reasoning on a purely hypothetical basis, (36) and taking into account the information contained in the documents before the Court, I can usefully proceed only on the basis put forward by the Commission and the United Kingdom, whereby SS is to be assimilated to a `starting material' within the meaning of the `standards and protocols' directive. (37)
54 The expression `starting material' should be understood as meaning `... all the constituents of the ... medicinal product and, if necessary, of its container, as referred to in point A, paragraph 1.' (38)
55 That latter provision provides that the constituents of medicinal products are:
- the active ingredient(s),
- the constituent(s) of the excipient(s) whatever their nature or the quantity used, including colouring agents, preservatives, stabilisers, thickeners, emulsifiers, anti-agglutinating agents, flavouring and aromatic substances, propellants, etc.,
- the constituents of the pharmaceutical form intended to be ingested or otherwise administered to animals.
(1)
Information concerning the manufacturing processes of a starting material
56 Article 5, second paragraph, point 4 of Directive 81/851 provides that the information and documents submitted in support of an application for marketing authorisation must include a `brief description of the method of preparation'. (39)
57 The `standards and protocols' directive provides that the brief description of the method of preparation must include at least:
`- mention of the various stages of manufacture, so that an assessment can be made of whether the processes employed in producing the pharmaceutical form might have produced an adverse change in the constituents;
...
- the actual manufacturing formula, with the quantitative particulars of all the substances used, the quantities of excipients, however, being given in approximate terms in so far as the pharmaceutical form makes this necessary; mention shall be made of any substances which may disappear in the course of manufacture;
- a statement of the stages of manufacture at which sampling is carried out for in-process control tests, where other data in the documents supporting the application show such tests to be necessary for quality control of the proprietary medicinal product.' (40)
58 I therefore have to conclude that, in answer to the questions of the referring court, the requirement that an applicant for marketing authorisation must provide particulars of the manufacturing method of the disputed product, in so far as it constitutes a starting material, is in accordance with the provisions of Directives 81/851 and 81/852.
(2)
Particulars of the control methods used by the manufacturer of a starting material
59 In Question 1(b), the national court amplifies one of the aspects of Question 1(a), by asking whether a national practice consisting, among other things, in requiring a person responsible for marketing a veterinary medicinal product to submit for approval the results of tests on each batch of the disputed product purchased by him is permissible.
60 Article 5, second paragraph, point 9 of Directive 81/851 provides that an application for marketing authorisation must contain a `description of the control testing methods employed by the manufacturer (qualitative and quantitative analysis of the constituents and the finished product, specific tests, e.g. sterility tests, tests for the presence of pyrogens, for the presence of heavy metals, stability tests, biological and toxicity tests, tests on intermediate products).' (41)
61 The `standards and protocols' directive provides that `the particulars and documents accompanying the application for marketing authorisation pursuant to points 9 and 10 of the second paragraph of Article 5 of Directive 81/851/EEC must include the results of the tests relating to quality control of all the constituents used. These shall be submitted in accordance with the following provisions ...'. (42)
There follows an exhaustive list of provisions to be complied with in order to meet the statutory requirements, which makes a distinction according to whether the starting materials are listed (43) or not listed (44) in pharmacopoeias. (45)
62 It is clear from the analysis of part C of the first protocol of the Annex to Directive 81/852 that the concern of the Community legislature is, above all, to check that the starting material, whether listed in a pharmacopoeia or not, was prepared according to a method which cannot leave impurities. (46)
63 By way of example, if the starting material used is not listed in any pharmacopoeia, it must be the subject of a monography concerning `purity tests ... described in relation to the sum total of predictable impurities, especially those which may have a harmful effect, and, if necessary, those which, having regard to the combination of substances to which the application refers, may adversely affect the stability of the medicinal product or distort analytical results.' (47)
However, if the starting material used is listed in the pharmacopoeias, it is to be verified that it `... has been prepared by a method liable to leave impurities not mentioned in the pharmacopoeia monograph.
These impurities and their maximum tolerance levels must be declared and a suitable test method advanced'. (48)
64 Moreover, I think that it is important to point out, having regard to the kind of dispute now before the Court - and although this concerns only a factual matter - that the Commission expert emphasised that the risk of any impurities existing in the product in question spreading in the DHS was not negligible, in particular because of the use of boron in the SS manufacturing process.
That is why this expert concluded that it is very important to be able to know the manufacturing methods used by SS producers in order to set up the appropriate tests.
Again, still according to the Commission expert, controls based on analytical tests of the active ingredient (DHS), of the final product (Pen & Strep) or the starting material itself (SS) would be insufficient to exclude all risk of impurities in the final product.
That analysis was confirmed by the United Kingdom, (49) but contested by Norbrook.
65 Moreover, if the product in question is listed in a pharmacopoeia, the clarification requested by the national court in point (b) of its first question can also be answered since, in the Annex to Directive 81/852, it is stated that `the routine tests to be carried out on each batch of starting materials shall be declared in an application for authorisation to market.
These tests must make it possible to provide evidence that each batch of starting material satisfies the quality requirements of the relevant pharmacopoeial monograph'. (50)
However, as the Commission rightly points out, (51) in no case do Directives 81/851 and 81/852 provide for preliminary approval by the competent authorities of batches used in the manufacture of the medicinal product concerned.
66 Thus, I propose that the Court should reply to these points as follows:
a request for particulars of the control methods used by the manufacturer of starting materials is in conformity with the requirements of Directives 81/851 and 81/852.
Moreover, if the product in question is listed in the existing pharmacopoeias (52) - which is for the national court to determine - the requiring particulars of the results of tests on each batch of starting material is also in conformity with the provisions of Directives 81/851 and 81/852.
However, those directives preclude a competent authority from making the grant of a marketing authorisation for a veterinary medicinal product subject to approval of the batches of starting material entering into the manufacture of the medicinal product.
(3) Particulars of the manufacturer of a starting material
67 These particulars, (53) more precisely the names and addresses of the manufacturer or manufacturers and details of the site or sites of manufacture of a starting material, are not required by Directives 81/851 and 81/852.
Point 1 of the second paragraph of Article 5 of Directive 81/851 provides only that the person responsible for marketing must state the `name or corporate name and permanent address or registered place of business of the person responsible for marketing and of the manufacturer, if different'.
By `manufacturer' must be understood the manufacturer of the medicinal product, the finished product, and not the manufacturer of each constituent.
68 To the list of information to be provided by the person responsible for the marketing of a veterinary product Directive 92/18 added this requirement:
`The name and address of the applicant shall be given, together with the name and address of the manufacturers and the sites involved in the different stages of the manufacture (including the manufacturer of the finished product and the manufacturer(s) of the active ingredient(s), and where relevant the name and address of the importer'. (54)
This provision is not, however, applicable in this case.
69 At the hearing, the United Kingdom accepted that these particulars were not mentioned in Directive 81/851 as being particulars which must be appended to applications for the grant of a marketing authorisation for a veterinary medical product and that it had requested them in order to be able to get in touch directly with the manufacturers of the product in question in order to obtain the information about the manufacturing process and control methods for the preparation of SS which was lacking in Norbrook's application documents.
It states that point 3 of the first paragraph of Article 9 of Directive 81/851 allows it to demand this further information. (55)
70 That article provides that the competent authority `[may], where appropriate, require the applicant to provide further information as regards the items listed in Article 5'. (56)
71 I think that not only the requirements imposed by the United Kingdom are contrary to Directives 81/851 and 81/852 but also that point 3 of the first paragraph of Article 9 of Directive 81/851 is not applicable in this case.
72 Directives 81/851 and 81/852 require the competent authorities of each Member State to make the grant of marketing authorisations subject to observance of all the conditions expressly laid down by them and do not authorise a Member State to prescribe others.
73 This is clear from the wording of a number of provisions of those directives.
74 Thus, Article 11 of Directive 81/851 provides that: `The authorisation provided for in Article 4 shall be withheld if examination of the documents and particulars listed in Article 5 establishes that: ... . (57) Authorisation shall also be withheld if the application documents submitted to the competent authorities do not comply with Articles 5, 6 and 7'. (58)
75 Similarly, point 1 of the first paragraph of Article 9 of Directive 81/851 provides that:
`In order to examine the application submitted pursuant to Article [5], the competent authorities of the Member States:
1. shall check that the documentation submitted in support of the application complies with Article 5 and, on the basis of the reports drawn up by the experts pursuant to Article 7, ascertain whether the conditions for the issue of the marketing authorisation have been fulfilled.'
76 Or take the first paragraph of Article 1 of the `standards and protocols' Directive, which, as we have seen, states:
`Member States shall take all appropriate measures to ensure that the particulars and documents which shall accompany applications for authorisation to place a veterinary medicinal product on the market pursuant to points 3, 4, 6, 8, 9 and 10 of the second paragraph of Article 5 of Directive 81/851/EEC, are submitted by the persons concerned in accordance with the Annex to this Directive'. (59)
77 It seems to me that, by using the present indicative, the present subjunctive, the adverbs `also' and `in accordance with', verbs expressing an obligation or a prohibition such as `shall' and `refuse', the Community legislature clearly expressed its intention to make the grant of marketing authorisation subject to observance of all the precise and unconditional conditions of those directives and if the particulars required by Article 5 are not given, as is the case here, a marketing authorisation must be refused.
78 Moreover, the interpretation according to which all the requirements of Article 5 of Directive 81/851, submitted in accordance with the Annex to Directive 81/852, must be observed has the purpose of ensuring the attainment of the aim of protecting public health. (60)
I have previously explained the risks which could be involved in non-observance of points 3, 4 and 9 of the second paragraph of Article 5 of Directive 81/851 (61) as regards public health.
79 Finally, the Court held in its judgment in the Scotia Pharmaceuticals case, (62) cited above, which is transposable to this case, (63) that all the requirements of the directives concerning the grant of marketing authorisations for medicinal products for human use must be observed.
80 Moreover, the first and second indents of the first paragraph of Article 41 of Directive 81/851 state:
`No decision to:
- withhold, withdraw or suspend marketing authorisation,
- prohibit the supply of a veterinary medicinal product or have it withdrawn from the market,
- ...
may be taken on grounds other than those set out in this Directive'. (64)
81 The wording of that article is clear.
It requires the Member States not to add other requirements to those laid down by the directives as regards the grant, withdrawal, refusal and suspension of marketing authorisation.
82 The purpose of observance of the requirements of Article 41 of Directive 81/851 is to ensure attainment of the aim of providing freedom of movement for medicinal products: `Whereas standards and protocols for the performance of tests and trials on veterinary medicinal products ... can facilitate the movement of these products by laying down uniform rules applicable to tests and trials and the compilation of dossiers'. (65)
83 In my view, allowing the Member States to demand other information than that provided for by Article 5 of Directive 81/851 would amount to authorising the competent authorities to substitute the sufficiently precise and unconditional requirements of the directive with other requirements unilaterally decided upon, with the consequence that there would be a risk of jeopardising the aim of harmonising national procedures for delivery of marketing authorisations for veterinary medicinal products, which is a clearly stated aim, (66) and thereby jeopardising the free movement of medicinal products.
84 The Court has also held that only the matters exhaustively listed by the harmonising directives on marketing authorisation for medicinal products for human use may be required by the competent authority. (67)
85 The conclusion must therefore be that Directive 81/851 precludes a national practice consisting in demanding information about the manufacturer of the starting material.
86 It follows from the foregoing that point 3 of the first paragraph of Article 9 of Directive 81/851 may not be interpreted as authorising a Member State to demand particulars other than those strictly listed by the aforementioned directives, but only as permitting Member States to demand from an applicant for marketing authorisation further information about a particular previously given, in accordance with the provisions of Article 5, where information is judged incomplete with regard to the requirements of public health.
This would be the case, for example, if, having regard to scientific progress, Member States considered that additional information would be of use for checking the harmlessness and therapeutic effectiveness of a product. (68) Similarly, in my view, it affords them the right, as I will examine below, (69) to suspend a marketing authorisation pending receipt only of particulars expressly listed in Article 5.
The requirements imposed by Directives 81/851 and 81/852 regarding refusal and suspension of marketing authorisations
87 Secondly, points (c) and (d) of the first preliminary question ask the Court in substance to determine whether, in circumstances such as those described in the order for reference, Directives 81/851 and 81/852 are to be interpreted as authorising a competent authority to refuse or suspend marketing authorisation for a veterinary medical product if the person responsible for marketing has not complied with the aforementioned requirements. (70)
(1) Refusal to issue marketing authorisation
88 The national court asks in point (c) of this first question, precisely, whether the provisions of the directives in question allow a competent authority like the VMD to refuse to issue a marketing authorisation for a veterinary medicinal product like Pen & Strep if the person responsible for marketing (Norbrook) has not provided particulars about the manufacturer, about the results, with a view to their approval, of control tests carried out on each batch of starting material, about the manufacturing process and about the control methods used by the manufacturer of the starting material (SS).
89 I refer to my arguments relating to examination of the requirements imposed by the aforementioned directives regarding grant of marketing authorisation in so far as I perceive no difference between the two questions.
90 When examining those questions, I emphasised that a competent authority is obliged to make grant of marketing authorisation subject to observance of all the conditions listed by Article 5 of Directive 81/851.
A fortiori that authority must refuse to grant marketing authorisation for a veterinary medicinal product if one of the items of information required by Article 5 of Directive 81/851 is missing.
91 On the other hand, I have stated that it cannot make the grant of marketing authorisation subject to the making available of particulars which are not listed by that provision.
Similarly and a fortiori, it cannot refuse to grant marketing authorisation on the ground that documents and information not expressly stipulated by the directives are lacking.
92 The Court is further asked to determine whether the provisions of the aforementioned directives permit the VMD to make grant of this marketing authorisation subject to proof of purchase of quantities of active ingredients from a specified third party.
93 No provision in the directives in question authorises the competent authority to require an applicant for marketing authorisation to obtain supplies from a manufacturer which it approves.
94 For the reasons explained above, the conclusion must therefore be that a competent authority cannot refuse to grant marketing authorisation for a veterinary medicinal product either on the ground that particulars of the manufacturer of the product in question are missing or on the ground that active ingredients have not been obtained from an approved manufacturer, or on the ground that batches of the starting material used in the manufacture of the medicinal product have not been previously approved. On the other hand, it must refuse to grant a marketing authorisation for the medicinal product if the particulars of the manufacturing process and of the control methods used by the manufacturer of the starting material are not contained in the application documents.
(2) Suspension of marketing authorisation
95 In point (d) of its first question the national court asks the Court to interpret the provisions of Article 8 of Directive 81/851 and to determine whether the competent authority may suspend the time-limit for grant of a marketing authorisation until the applicant has supplied the information relating to the manufacturing process, control methods and the manufacturer.
96 I consider that it follows expressly from a reading of the combined provisions of Article 8 and point 3 of the first paragraph of Article 9 of Directive 81/851 and from the ratio legis of the relevant legislation that the period for the grant of marketing authorisation may indeed be suspended until the applicant has supplied the information required by Article 5 of Directive 81/851.
On the other hand, it may not be suspended in the case of information not expressly required by Directives 81/851 and 81/852, such as names and addresses of the manufacturer or manufacturers of the starting material and the site or sites of manufacture.
97 As far as the wording of the relevant provisions are concerned:
The first paragraph of Article 8 of Directive 81/851 provides:
`Member States shall take all appropriate measures to ensure that the procedure for granting marketing authorisation is completed within 120 days after the date of submission of the application.'
The first paragraph of point 3 of Article 9 provides, as already stated:
`[The competent authorities] may, where appropriate, require the applicant to provide further information as regards the items listed in Article 5.
Where the competent authorities take this course of action, the time-limits specified in Article 8 shall be suspended until the further data required have been provided.
Similarly, these time-limits shall be suspended for any period which the applicant may be given to provide oral or written explanations'. (71)
98 Instead of immediately refusing to grant a marketing authorisation to an applicant who has not provided full information, (72) the competent authorities may take the course of suspending the authorisation for as long as the missing documents have not been appended. (73)
99 The verb `compléter' means in fact `to add what is missing' and not `to add something else' or `supply something else'. (74)
Thus, in accordance with what I have argued previously, the competent authorities may not demand any information other than that expressly prescribed by the directive and may suspend the marketing authorisation only for the reasons it expressly mentioned. (75)
100 The ratio legis of the legislation on marketing authorisation for veterinary medicinal products is in accordance with that interpretation.
As we have seen, the aims which it pursues are to protect public health and ensure freedom of movement for veterinary medicinal products. (76)
The means chosen to attain these aims consisted in harmonising national procedures for issue, suspension and refusal of marketing authorisations. (77) To suspend the grant of a marketing authorisation pending receipt of information which must be compulsorily appended to the application is therefore in strict accordance with the aims pursued by the Community legislature.
101 It follows from the foregoing that the competent authorities have the right to suspend the period for grant of the marketing authorisation laid down in Article 8 of Directive 81/851 for as long as the applicant has not supplied the information on the manufacturing process and on the control testing methods for the starting material.
102 On the other hand, and I here refer to my arguments concerning the examination of the requirements laid down by Directives 81/851 and 81/852 concerning the grant of a marketing authorisation in so far as I perceive no difference between the two questions, (78) a competent authority may not suspend grant of a marketing authorisation if an item of information not expressly stipulated by Directives 81/851 and 81/852, such as the identity of the manufacturer and the sites of manufacture, is missing.
The second question
103 By this question, the national court asks the Court to state whether the replies given to the first question would be appreciably different if a substance such as SS was produced by a `continuous' process, that is to say by a process in which the constituents are not separated.
104 It must be deduced from a reading of the account of the method of manufacturing the medicinal product that neither SS nor DHS are made according to a process which consists in mixing the constituents:
`The Applicant produces DHS from SS by "reduction" or "hydrogenation", whereby the molecular structure of the [product in question] is altered.
This latter process involves the use of a catalyst called sodium borohydride, which contains the element boron.
Once the DHS has been produced it is mixed with the other active ingredient [PP], and the non-active ingredients (known as "excipients") to make the final product Pen & Strep'. (79)
Production by continuous process does not therefore occur until after the manufacture of DHS.
105 According to the Court's established case-law, (80) where it clearly appears that the interpretation of Community law is not relevant for the outcome of the proceedings, the second question is redundant.
The third question
106 If the demands made by the competent authority are in conformity with the provisions of Directives 81/851 and 81/852, the national court asks, by this question, whether those directives contain provisions which would allow the person responsible for marketing to be exempt from providing the items of information and, if so, on what conditions.
107 In Scotia Pharmaceuticals, cited above, the Court has already had to reply to such a question concerning marketing authorisation for a medicinal product for human use.
In that case the Court held that the tests and particulars listed by the directives in force had to be appended to the application for marketing authorisation and that only scientific progress could entail a change in the information to be supplied for the purposes of the grant of marketing authorisation. (81)
The sixth question
108 By this question the national court asks for an interpretation of the provisions of Article 40 of Directive 81/851 and whether reasons must be given for the various requests for information made in this case by the VMD as regards the decisions to suspend and refuse marketing authorisation mentioned in the preliminary questions previously examined.
If the answer is in the affirmative, the Court is asked to state the conditions which must be observed by the competent authority if they are to be regarded as in conformity with the provisions of that article.
109 The first paragraph of Article 40 of Directive 81/851 provides:
`All decisions taken pursuant to Articles 11, (82) 36, (83) 37 (84) and 38, (85) ... and all decisions to withdraw authorisation to manufacture or to import from third countries or to suspend or withdraw manufacturing authorisation shall state in details the reasons on which they are based.
Such decisions shall be notified to the party concerned who shall at the same time be informed of the remedies available to him under current legislation and the time allowed for seeking such remedies.'
110 The wording of the first paragraph of Article 40 of Directive 81/851, read in combination with the articles to which it refers, is very clear.
It lists the cases in which the competent authority must give reasons for its decisions.
The competent authorities are only obliged to state reasons for decisions to refuse, withdraw or suspend a marketing authorisation for a veterinary medicinal product from a Member State or a third country.
The provision does not therefore apply to demands for supplementary information made by the VMD during examination of applications for marketing authorisations.
111 It is stated that the reasons given must be detailed, that they must be notified to the party concerned who at the same time must be informed of the remedies available to him under current legislation and of the time allowed for seeking such remedies.
112 As regards the obligation to state in detail the reasons for the decisions in question, I consider that reasons which show clearly and unequivocally why a competent authority has refused, withdrawn or suspended a marketing authorisation meets the requirements of Article 40.
This will be the case, for example, with reasons indicating the particulars and items of information missing.
Replies to questions concerning determination of the validity of Directives 81/851 and 81/852
113 In the event of an affirmative answer to the first question, the Court is asked, in the fourth and fifth questions, to determine the validity of the provisions of Directives 81/851 and 81/852 with reference to the principles of proportionality and free movement of goods.
The fourth question:
breach of the principle of proportionality
114 By this question, the Irish court would appear to be asking the Court to determine whether the requirements and requests for information made by the VMD and examined in the first question are contrary to the principle of proportionality.
115 In my view, a distinction must be made between such requests, according to whether or not they are prescribed by Directives 81/851 and 81/852.
116 If they are not provided for by those directives (as is the case with requirements concerning prior approval of each batch of SS or DHS or of the sites of manufacture of SS), there are no grounds for them to be made, and any application of the principle of proportionality will be redundant.
117 On the other hand, in the case of demands required to be made by those directives, it will indeed be necessary to determine whether those stipulations comply with that principle.
As far as I know, this is the first time that the Court has been asked to do this.
118 The precise question put to the Court is whether point 4 of the second paragraph of Article 5 of Directive 81/851 and the stipulations contained in the first to fourth indents of the first and second paragraphs of Part B of the first Protocol of the Annex to Directive 81/852, relating to the description of the method of preparation of starting materials, and point 9 of the second paragraph of Article 5 of Directive 81/851 and the stipulations in Part C of the first Protocol of the Annex to Directive 81/852, relating to the description of the methods of control for the starting materials used by the manufacturer, are in accordance with the principle of proportionality.
119 This general principle of Community law requires that acts of Community institutions must not exceed the limits of what is appropriate and necessary for attaining the objectives legitimately pursued by the legislation in question.
When there is a choice between several appropriate measures, recourse must be had to the least onerous, and the disadvantages caused must not be disproportionate to the aims pursued. (86)
120 The very high level of requirement imposed by those provisions for the marketing of a veterinary medical product is in conformity with the aim of providing absolute protection for public health pursued by that legislation.
121 Moreover, owing to the very purpose of Directives 81/851 and 81/852, the Community legislature must assess complex situations since it is a question of legislating on the basis of technical and scientific factors which can change rapidly.
I therefore consider that its assessment is to be censured only if it appears to be manifestly incorrect in view of the information it had at the time of the adoption of the legislation or if the institution adopting the measure in question committed a misuse of power or manifestly exceeded the limits of its discretion. (87)
122 Norbrook claims (88) that the principle of proportionality has been contravened in that, in particular `... the nature of this requirement, in particular the frequent impossibility of compliance and the consequences of such non-compliance, is wholly out of proportion to such infinitesimal risk to public health ... which might result from ignorance ... of [SS] manufacturing processes'. (89)
123 The Court has held that the provisions of directives harmonising marketing authorisations for medicinal products for human use `... cannot be interpreted as requiring the performance of tests which are in practice impossible to carry out.' (90) The argument that the requirements are `difficult to satisfy' is not relevant in view of the interests in question, those of public health.
124 In so far as no conclusive evidence has been adduced concerning any manifest error of assessment or misuse of power on the part of the Community legislature, it must be found that there is no factor to support the conclusion that the principle of proportionality has been contravened.
The fifth question:
breach of Articles 30 to 36 of the Treaty
125 The national court also asks whether the VMD's demands for information under Directives 81/851 and 81/852 are in breach of Articles 30 to 36 of the Treaty.
126 The Court has already answered this question in its judgment in the Bruyère case by stating that `although Directive 81/851 describes itself as "one stage in the achievement of the aim of freedom of movement of veterinary medicinal products" (11th recital in the preamble), it cannot be inferred from this that, for medicinal products coming within its scope, the directive leaves room for the application of Articles 30 and 36 of the Treaty.
As the development of Community law shows, that wording means only that the system of multiple national authorisations for the marketing of products, first introduced by Directive 81/851, was destined to be replaced by a system under which account was to be taken of authorisations granted by other Member States (Directive 90/676) and subsequently by a system for the mutual recognition in principle of such authorisations (Directive 93/40)'. (91)
127 In the present case, the medicinal product Pen & Strep does fall within the scope of Directives 81/851 and 81/852. Accordingly, its marketing is subject to issue of a marketing authorisation by the VMD, which must observe all the legal provisions in force.
128 It must therefore be concluded that there is no factor enabling it to be concluded that a breach of Articles 30 to 36 of the Treaty has occurred.
Answers to the questions concerning the conditions under which a Member State incurs liability for breach of Community law
The seventh question
129 Finally, by this question, the Court is asked to make clear the conditions under which a Member State incurs liability for breach of Community law.
130 The Court's case-law is now well-established and in a judgment of 8 October 1996 in the Dillenkofer case (92) the Court clearly and precisely reiterated the conditions under which a Member State incurs liability for breach of Community law.
131 The Court has held (93) that individuals who have suffered damage have a right to reparation where three conditions are met:
the rule of Community law infringed must have been intended to confer rights on them;
the breach must be sufficiently serious;
and there must be a direct causal link between that breach and the damage sustained by the individuals. (94)
132 As regards the condition concerning a sufficiently serious breach of a rule of Community law, the Court has also held that it is fulfilled `if ... a Member State, in the exercise of its rule-making powers, manifestly and gravely disregards the limits on those powers' and that `if, at the time when it committed the infringement, the Member State in question was not called upon to make any legislative choices and had only considerably reduced, or even no discretion, the mere infringement of Community law may be sufficient to establish the existence of a sufficiently serious breach ... .' (95)
133 As we have seen above, the provisions of Directives 81/851 and 81/852 are precise and sufficiently clear for it to be said that the discretion left to the Member States when they transpose those directives is extremely reduced, (96) or even non-existent.
134 Therefore, where, in breach of the third paragraph of Article 189 of the Treaty, a Member State incorrectly transposes or misapplies sufficiently clear and precise provisions of the aforementioned directives, that Member State manifestly and gravely disregards the limits on the exercise of its powers.
135 Consequently, such a breach affords individuals a right to obtain reparation if the result prescribed by the directive entails conferment on them of rights whose content may be identified on the basis of the provisions of the directive and if there is a causal link between the breach of the Member State's obligation and the damage suffered by the aggrieved persons, without there being any need to take into account other conditions.
Conclusion
136 In conclusion, for the reasons explained above, I propose that the questions submitted by the Court of Appeal in Northern Ireland should be answered as follows:
`1. Council Directive 81/851/EEC of 28 September 1981 on the approximation of the laws of the Member States relating to veterinary medicinal products and Council Directive 81/852/EEC of 28 September 1981 on the approximation of the laws of the Member States relating to analytical, pharmaco-toxicological and clinical standards and protocols in respect of the testing of veterinary medicinal products (and in particular Articles 5, 8, 9, 11, 29 to 31, 35, 40 and 41 of Directive 81/851/EEC and the first part of the Annex to Directive 81/852/EEC in the form in which they existed prior to any amendment) must be interpreted as:
(a) requiring the competent authority of a Member State, taking account of current technical developments and scientific progress, to make the grant of marketing authorisation for a veterinary medicinal product conditional upon the provision by the person responsible for the marketing of that medicinal product of information concerning the manufacturing and control methods used by the manufacturer of a starting material, and to refuse such authorisation if that information is not provided;
(b) permitting that authority to suspend, pending receipt of the abovementioned information, the time-limit for granting such authorisation prescribed in Article 8 of Directive 81/851.
(c) precluding that competent authority from:
(i)
suspending, pending receipt of the name(s) and address(es) of the manufacturer(s) and details of the manufacturing site(s) of the starting material, the time-limit prescribed in Article 8 of Directive 81/851 for granting such authorisation;
(ii)
making the grant of such authorisation conditional upon the submission for approval of the results of tests carried out upon each batch of the starting material, upon the use, for the manufacture of a veterinary medicinal product, only of supplies of the starting material and the active ingredient which were purchased from a specified third party, and upon the provision of information as to the name(s) and address(es) of the manufacturer(s) and the manufacturing site(s) of the starting material;
(iii)
refusing to grant such authorisation if the information referred to in (ii) above is not provided;
(d) requiring the competent authority to state reasons for any decision refusing, suspending or withdrawing marketing authorisation for a veterinary medicinal product.
This requirement is satisfied if the decision shows clearly and unequivocally the reasons for which that authority refused, suspended or withdrew such authorisation.
2. Examination of the provisions of the abovementioned directives, in the light of the grounds of the order for reference, has not revealed any factor of such a kind as to affect their validity.
3. A Member State is liable for damage suffered by individuals as a result of a breach of Community law for which it can be held responsible if the rule of Community law infringed was intended to confer rights on individuals, the breach is sufficiently serious, and there is a direct causal link between the breach and the damage suffered by the individuals.'
(1) - Council Directive 81/851/EEC of 28 September 1981 on the approximation of the laws of the Member States relating to veterinary medicinal products (OJ 1981 L 317, p. 1, hereinafter `Directive 81/851').
(2) - Council Directive 81/852/EEC of 28 September 1981 on the approximation of the laws of the Member States relating to analytical, pharmaco-toxicological and clinical standards and protocols in respect of the testing of veterinary medicinal products (OJ 1981 L 317, p. 16, hereinafter `the standards and protocols directive' or `Directive 81/852').
(3) - See paragraphs 14 to 31 of this Opinion.
(4) - See paragraph 36 of this Opinion.
(5) - Paragraph 2.7 of Norbrook's observations.
(6) - 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').
(7) - See, in particular, one of the most recent judgments in Case C-201/94 Smith & Nephew Pharmaceuticals v Primecrown [1996] ECR I-0000.
(8) - See, in particular, the second recital in the preamble to Commission Directive 92/18/EEC of 20 March 1992 modifying the Annex to Council Directive 81/852/EEC on the approximation of the laws of Member States relating to analytical, pharmacotoxicological and clinical standards and protocols in respect of the testing of veterinary medicinal products (OJ 1992 L 97, p. 1, hereinafter `Directive 92/18').
(9) - 11th recital in the preamble to Directive 81/851.
(10) - I have found only one previous judgment concerning the interpretation of Article 4 of Directive 81/851.
It was given in Case C-297/94 Bruyère and Others v Belgian State [1996] ECR I-1551.
(11) - Articles 6 and 29 to 31 of Directive 81/851.
(12) - Ibid., Article 7.
(13) - Emphasis added.
(14) - First paragraph of Article 1 of Directive 81/852.
(15) - i.e. physico-chemical, biological or microbiological tests.
(16) - i.e. the study of the effects of the veterinary medicinal product on the animal organism.
(17) - i.e. the study of what happens to the veterinary medicinal product in the animal organism.
(18) - The aim of these trials is to demonstrate or verify the therapeutic effect of the product, specify its indications and counter-indications by reference to species, age, methods of use, and safety under normal conditions of use.
(19) - Paragraph 38 et seq. of this Opinion.
(20) - Section 7(2) of the 1968 Act.
(21) - Ibid., Sections 18 and 19, and the Medicines (Applications for Product Licences and Clinical Trial and Animal Test Certificates) Regulations 1971, as amended, S.I. 1971 No 973 (`the 1971 Regulations').
(22) - A list of which appears in Schedule 1, Part 1 of the 1971 Regulations.
(23) - See paragraphs 6 to 9 of this Opinion.
(24) - Directive 65/65; Council Directive 75/318/EEC of 20 May 1975 on the approximation of the laws of Member States relating to analytical, pharmaco-toxicological and clinical standards and protocols in respect of the testing of proprietary medicinal products (OJ 1975 L 147, p. 1); 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 (OJ 1975 L 147, p. 13).
(25) - Paragraph 21, emphasis added.
(26) - Compare, for example, Articles 3, 4, 5, 7, 8, 12 and 21 of Directive 65/65 with Articles 4, 5, 8, 9, 11, 40 and 41 of Directive 81/851; Article 1 of Directives 75/318 and 81/852 respectively; the first protocols of the annex to Directives 75/318 and 81/852 respectively; and Article 2 of Directive 75/319 with Article 7 of Directive 81/851.
(27) - Compare the judgment in Scotia Pharmaceuticals, cited above, paragraph 3, with the judgment in Bruyère and Others, cited above, paragraph 2.
(28) - First protocol of the Annex to Directive 81/852, Part A, point 1, first paragraph, first, second and third indents.
(29) - Page 3 of the order for reference.
(30) - Not disputed by any of the parties, including Norbrook; see paragraph 1.4 of its observations.
(31) - Second part of the first protocol of the Annex to Directive 92/18, Part C, first and second sub-paragraphs of paragraph 2, emphasis added.
(32) - Paragraph 13 of the United Kingdom's observations.
(33) - First paragraph of Part A of the first protocol of the Annex to Directive 81/852.
(34) - This provision, which deals with the control methods used by the manufacturer, will be considered in detail in the context of the answers to be given to Question 1.
(35) - Paragraph 21.
(36) - Prohibited by the judgment in Case C-83/91 Meilicke v ADV/ORGA [1992] ECR I-4871.
(37) - No other facts or arguments have been adduced to allow me to argue cogently on any other basis, because, although Norbrook denies that SS is to be assimilated to a starting material, it does not adduce any facts or arguments to enable me seriously to consider any possibility other than that put forward by the Commission and the United Kingdom.
Thus, in Norbrook's submission, the disputed product is neither an active ingredient, nor an excipient, nor a starting material, nor a constituent, but only a `substance' (points 2.4 and 2.8 of its observations).
(38) - First paragraph of Part C of the first protocol of the Annex to the `standards and protocols' directive, emphasis added.
(39) - Emphasis added.
(40) - First protocol of the Annex to the `standards and protocols' directive, Part B, second paragraph, first, third and fourth indents, emphasis added.
(41) - My emphasis.
(42) - Second paragraph of Part C of the first protocol of the Annex to Directive 81/852, concerning the control of starting materials, emphasis added.
(43) - Point 1 of Part C of the first protocol of the Annex to Directive 81/852.
(44) - Ibid., point 2.
(45)Definition given in the Nouveau Larousse Médical: `Compendium containing: the nomenclature of drugs, simple and composite medicinal products, medicinal articles; a list of common names for medicines; tables of maximum and normal dosages of medicinal products for [the animal]; information which may be useful to a pharmacist for pharmaceutical practice'.
(46) - See, in particular, point 1 of part C of the first part of the Protocol of the Annex to Directive 81/852, paragraphs 4, 5 and 7, and point 2 of part C, at (b), (d) and (e).
(47) - First paragraph of point 2(d) of part C of the first Protocol of the Annex to Directive 81/852.
(48) - Fourth paragraph of point 1 of the part C of the first Protocol of the Annex to Directive 81/852.
(49) - First paragraph of the French translation of its observations.
(50) - Ibid., seventh paragraph, my emphasis.
(51) - Under the heading `Answer to question 1b' on page 9 of the Commission's observations.
(52) - The participating parties are unanimous that this is the case.
(53) - Point (a) of the first preliminary question.
(54) - Second paragraph of section A of Part 1 of Title I of the Annex to Directive 92/18.
(55) - Point 14 of the United Kingdom Government's observations.
(56) - My emphasis.
(57) - Ibid., first paragraph, my emphasis.
(58) - Ibid., second paragraph, my emphasis.
(59) - My emphasis.
(60) - Third recital of the preamble to the `standards and protocols' directive, my emphasis:
`Whereas standards and protocols for the performance of tests and trials on veterinary medical products are an effective means of control of these products and, hence, of protecting public health ... .'
(61) - Paragraphs 62 to 65 of my Opinion.
(62) - Paragraph 21.
(63) - Paragraph 42 of my Opinion.
(64) - My emphasis.
(65) - Third recital of the preamble to the `standards and protocols' directive, my emphasis.
(66) - Second, third, fourth and ninth recitals of the preamble to Directive 81/851;
first, second, third and fourth recitals of the preamble to the `standards and protocols' directive.
(67) - Case 301/82 Clin-Midy and Others [1984] ECR 251, paragraph 11, and Case C-83/92 Pierrel and Others [1993] ECR I-6419, paragraphs 21 to 23.
(68) - Article 14 of Directive 81/851.
(69) - See paragraphs 96 to 101 of my Opinion.
(70) - See paragraphs 56 to 86 above.
(71) - My emphasis.
(72) - See, in particular, paragraph 77 of my Opinion.
(73) - Paragraph 86 above.
(74) - In comparison with the French, Italian, Dutch, German and Spanish versions of the provision, the English version is less precise since it provides:
`may, where appropriate, require the applicant to provide further information as regards the items listed in Article 5' (my emphasis).
(75) - See, to this effect, the judgment in Pierrel, cited above, paragraphs 28 and 33.
(76) - Paragraphs 18, 78 and 82 of my Opinion.
(77) - Third, fourth and eighth recitals of the preamble to Directive 81/852.
(78) - Paragraphs 67 to 86 of my Opinion.
(79) - Paragraph 3 of the order for reference.
(80) - See, in particular, a judgment delivered on 5 October 1995 in Case C-96/94 Centro Servizi Spediporto [1995] ECR I-2883.
(81) - Paragraphs 41 and 49 of my Opinion.
(82) - Provision listing the cases in which marketing authorisation which must be refused.
(83) - Provision listing the cases in which marketing authorisation must be suspended or withdrawn.
(84) - Provision listing the cases in which marketing authorisation must be withdrawn.
(85) - Provision listing the cases in which marketing authorisation must be suspended or withdrawn.
(86) - See, in particular, the judgment in Case 265/87 Schräder [1989] ECR 2237, paragraph 21, and, more recently, the judgment in Case C-84/94 United Kingdom v Council, not yet published in the ECR, paragraph 57.
(87) - See, in particular, the judgment in United Kingdom v Council, cited above, paragraph 58, or the judgment in Joined Cases C-296/93 and C-307/93 France and Ireland v Commission [1996] ECR I-795, paragraphs 30 and 31.
(88) - Pages 43 to 47 of its observations.
(89) - Ibid., paragraph 11.4.
(90) - Case C-40/93 Scotia Pharmaceuticals, cited above, paragraph 21.
(91) - Paragraph 18.
(92) - Joined Cases C-178/94, C-179/94, C-188/94, C-189/94 and C-190/94, not yet published in the ECR.
(93) - Joined Cases C-6/90 and C-9/90 Francovich and Others [1991] ECR I-5357;
Joined Cases C-46/93 and C-48/93 Brasserie du Pêcheur and Factortame and Others [1996] ECR I-1029;
Case C-392/93 British Telecommunications [1996] ECR I-1631;
and Case C-5/94 Hedley Lomas [1996] ECR I-2553.
(94) - Dillenkofer, cited above, paragraphs 21 and 23.
(95) - Ibid., paragraph 25, my emphasis.
(96) - Point 41 of my Opinion.