Opinion of the Advocate-General



Opinion of the Advocate-General

1. In the present case, the Verwaltungsgericht Köln (Administrative Court, Cologne) (Germany) asks the Court whether Commission Regulation (EC) No 1873/2003 of 24 October 2003 amending Annex II to Council Regulation (EEC) No 2377/90 laying down a Community procedure for the establishment of maximum residue limits of veterinary medicinal products in foodstuffs of animal origin (2) is compatible with Articles 1(1) and 3 of Council Regulation (EEC) No 2377/90 (3) and Article 4(1) of Council Directive 96/22/EC of 29 April 1996 concerning the prohibition on the use in stockfarming of certain substances having a hormonal or thyrostatic action and of beta-agonists, and repealing Directives 81/602/EEC, 88/146/EEC and 88/299/EEC. (4)

2. The preliminary reference arose in an action brought by cp-Pharma Handels GmbH (hereinafter ‘cp-Pharma’) against the competent national authorities following the revocation of its marketing authorisation for the veterinary medicinal product ‘progesterone ad us. vet’ in the form of a solution for intramuscular injection.

I – Relevant Community law

A – Regulation No 2377/90

3. Regulation No 2377/90 lays down a Community procedure for the establishment of maximum residue limits (‘MRLs’) of veterinary medicinal products in foodstuffs of animal origin.

4. Article 1(1)(a) of Regulation No 2377/90 provides that ‘“residues of veterinary medicinal products”: means all pharmacologically active substances, whether active principles, excipients or degradation products, and their metabolites which remain in foodstuffs obtained from animals to which the veterinary medicinal product in question has been administered’. Article 1(1)(b) of Regulation No 2377/90 provides that the ‘“maximum residue limit”: means the maximum concentration of residue resulting from the use of a veterinary medicinal product … which may be accepted by the Community to be legally permitted or recognised as acceptable in or on a food’.

5. Articles 2 to 5 of Regulation No 2377/90 provide for four annexes to be drawn up in which pharmacologically active substances, intended for use in veterinary medicines to be administered to food-producing animals, may be included:

– Annex I is reserved for substances for which an MRL may be established following an assessment of the risks which the substance presents to human health (Article 2);

– Annex II is reserved for substances in respect of which it does not appear necessary, for the protection of public health, to fix an MRL (Article 3); (5)

– Annex III is reserved for substances for which it is not possible to establish an MRL definitively but for which, without compromising consumer health, a provisional MRL may be established for a fixed period which can only be extended once (Article 4);

– Annex IV is reserved for substances for which no MRL can be established because residues of such substances constitute a threat to consumer health in any amount (Article 5).

6. Article 6(1) of Regulation No 2377/90 provides that ‘[i]n order to obtain the inclusion in Annexes I, II or III of a pharmacologically active substance which is intended for use in veterinary medicinal products for administration to food-producing animals, an application to establish a maximum residue limit shall be submitted to the European Agency for the Evaluation of Medicinal Products set up by Council Regulation (EEC) No 2309/93, [(6) ] hereinafter referred to as “the Agency”.’

7. Article 7(1) of Regulation No 2377/90 provides that the ‘Committee for Veterinary Medicinal Products referred to in Article 27 of Regulation (EC) No 2309/93 (hereinafter “the Committee”) shall be responsible for formulating the Agency’s opinion on the classification of substances referred to in Annexes I, II, III or IV to this Regulation’.

8. Article 7(5) of Regulation No 2377/90 provides that ‘[t]he Agency shall forward the definitive opinion of the Committee within 30 days of its adoption both to the Commission and to the applicant. The opinion shall be accompanied by a report describing the safety evaluation of the substance by the Committee, which shall give the grounds for its conclusions.’

9. Article 7(6) of Regulation No 2377/90 provides that ‘[t]he Commission shall prepare draft measures taking account of Community legislation and shall start the procedure provided for in Article 8. …’

10. Article 8(1) of Regulation No 2377/90 provides that ‘[t]he Commission shall be assisted by the Standing Committee on Veterinary Medicinal Products’ (hereinafter ‘the Standing Committee’).

11. In its original version, Article 14 of Regulation No 2377/90 provided as follows:

‘With effect from 1 January 1997, the administration to food-producing animals of veterinary medicinal products containing pharmacologically active substances which are not mentioned in Annexes I, II or III shall be prohibited within the Community …’

12. Council Regulation (EC) No 434/97 of 3 March 1997 amending Regulation (EEC) No 2377/90 (7) deferred to 1 January 2000 the date initially fixed in Article 14 of Regulation No 2377/90 for most of the substances the use of which was authorised on the date of entry into force of the later regulation and in respect of which documented applications for the establishment of MRLs had been lodged before 1 January 1996. The substances in question included progesterone.

13. Article 15 of Regulation No 2377/90 provides, inter alia, that that regulation ‘shall in no way prejudice the application of Community legislation prohibiting the use in livestock farming of certain substances having a hormonal action’.

B – Directive 96/22

14. Article 3(a) of Directive 96/22, as amended by Directive 2003/74/EC of the European Parliament and of the Council of 22 September 2003 amending Council Directive 96/22/EC, (8) requires Member States, inter alia, to provisionally prohibit the administration to farm animals of substances having a gestagenic action, of which progesterone is one.

15. Article 4(1) of Directive 96/22, as amended, provides, inter alia, that notwithstanding the terms of Article 3, Member States may authorise the administering to farm animals, for therapeutic purposes, of progesterone. That provision also provides that veterinary medicinal products used for therapeutic treatment must comply with the requirements for placing on the market laid down in Council Directive 81/851/EEC. (9) Moreover, veterinary medicinal products may only be administered by a veterinarian, by injection or for the treatment of ovarian dysfunction in the form of vaginal spirals, but not by implant, to farm animals which have been clearly identified. Treatment of identified animals must be registered by the veterinarian responsible.

C – Regulation No 1873/2003

16. Article 1 of Regulation No 1873/2003 amended Annex II to Regulation No 2377/90 by inserting the pharmacologically active substance progesterone in that annex in relation to females of the animal species of bovine, ovine, caprine and equidae.

17. The inclusion of the active substance progesterone in Annex II to Regulation No 2377/90 was qualified by a note or footnote marked with an asterisk (*) and which provides as follows: ‘[o]nly for intravaginal therapeutic or zootechnical use and in accordance with the provisions of Directive 96/22/EC’.

D – Regulation (EC) No 178/2002 (10)

18. Article 7(1) of Regulation No 178/2002 provides that:

‘In specific circumstances where, following an assessment of available information, the possibility of harmful effects on health is identified but scientific uncertainty persists, provisional risk management measures necessary to ensure the high level of health protection chosen in the Community may be adopted, pending further scientific information for a more comprehensive risk assessment.’

II – Relevant national law

19. The first sentence of Paragraph 30(1) of the Law on Medicinal Products in the version published on 11 December 1998 (BGBl. 1998 I, p. 3586) (Arzneimittelgesetz) (‘AMG’) provides:

‘An authorisation shall be withdrawn if it subsequently becomes known that one of the grounds for refusal under Paragraph 25(2)(2), (3), (5), (5a), (6) or (7) existed at the time of issue; an authorisation must be revoked where one of the grounds for refusal under Paragraph 25(2)(3), (5), (5a), (6) or (7) subsequently arises.’

20. Paragraph 25(2)(7) of the AMG states:

‘The competent higher federal authority may refuse to grant an authorisation only if … the marketing of the medical product or its administration to animals would contravene legal provisions or a regulation, directive or decision of the Council or Commission of the European Communities …’

III – Legislative history leading to the adoption of Regulation No 1873/2003

21. In 1993 an application for the establishment of an MRL for progesterone in cattle and horses was submitted to the Commission. In October 1996, the Committee recommended that progesterone be included in Annex II to Regulation No 2377/90. In April 1997, the Commission sent new scientific information to the Agency and requested a re-assessment of the risks relating, inter alia, to progesterone. In April 1998, the Commission requested the Agency that the Committee should have the possibility to take account of scientific information which was to become available in the course of 1998 from a number of sources and the results of a number of specific studies commissioned by the Commission. In April 1999, the Commission asked the Agency to update the evaluation the former had requested in 1997 of progesterone. On 30 April 1999, the Scientific Committee on Veterinary Measures Relating to Public Health (‘the SCVPH’) issued a report which concluded, inter alia, that no acceptable daily intake could be established for the hormone progesterone. In December 1999, the Committee confirmed its earlier opinion recommending that progesterone be included in Annex II to Regulation No 2377/90. On 3 May 2000, the SCVPH adopted a re-evaluation of its opinion of April 1999. In its re-evaluation the SCVPH concluded that recent scientific information did not provide convincing data or arguments making a revision of its previous conclusions necessary. On 25 July 2001, the Commission adopted a proposal for a Council Regulation amending Annex I to Regulation No 2377/90 (11) classifying progesterone in that annex. That proposal was rejected by the Standing Committee which assists the Commission in accordance with Article 8 of Regulation No 2377/90. The Commission, pursuant to Article 8 of Regulation No 2377/90 submitted the proposal to the Council which was rejected in January 2002. In December 2002, the Commission submitted to the Standing Committee a second proposal classifying progesterone in Annex III to Regulation No 2377/90. That proposal did not obtain the favourable opinion of the Standing Committee. On 24 October 2003, the Commission adopted Regulation No 1873/2003 which lists progesterone in Annex II to Regulation No 2377/90, subject however to certain limitations. According to the 11th recital in the preamble to Regulation No 1873/2003, the measures provided for in that regulation are in accordance with the opinion of the Standing Committee.

IV – The main proceedings and the order for reference

22. By decision dated 16 February 1999, cp-Pharma’s marketing authorisation for the veterinary medicinal product ‘progesterone ad us. vet’ was extended for a five-year duration pursuant to Paragraph 105 of the AMG. According to the preliminary reference, the authorisation concerned ‘a solution for intramuscula r injection with the active substance progesterone in animals of bovine species, to be applied in cases of “follicle cysts”, “nymphomania caused by follicle cysts”’. By decision dated 22 January 2004, the competent national authorities revoked cp-Pharma’s authorisation on the grounds that following the amendment of Annex II to Regulation No 2377/90, as a result of the adoption of Regulation No 1873/2003, progesterone can only be administered via the intravaginal route. Given that no MRLs were established for other applications of that veterinary medicinal product, the prohibition contained in Article 14 of Regulation No 2377/90 applies to cp-Pharma’s product and its marketing authorisation must be revoked in accordance with Paragraph 30(1) in conjunction with Paragraph 25(2)(7) of the AMG.

23. cp-Pharma lodged an objection against that decision, which was rejected by the competent national authorities by decision dated 24 February 2004. In its action before the referring court, cp-Pharma submits that that court should annul the revocation of its marketing authorisation on the ground that the Commission unlawfully disregarded the recommendation of the Committee, which did not include a restriction to intravaginal application.

24. The referring court is uncertain whether the exclusion of progesterone administered by injection from the list in Annex II to Regulation No 2377/90 is compatible with Articles 1(1) and 3 of that regulation. That court expresses doubts, in the light of the ruling of the Court in Case C‑32/00 P Commission v Boehringer Ingelheim Vetmedica and C. H. Boehringer Sohn , (12) as to whether Article 3 of Regulation No 2377/90 empowers the Commission ‘to add restrictions concerning the manner of application to the list of substances in Annex II, when Articles 1(1) and 3 of Regulation [No 2377/90] do not establish limitations to prevent misuse’.

25. In that regard, the referring court notes that the Court observed that the only limitation on the validity of an MRL envisaged by Regulation No 2377/90 concerns the indication of the limited duration of its validity where the substance in question is entered in Annex III to that regulation. If this reasoning is applied to a substance which has no MRL and which is included in Annex II to Regulation No 2377/90, it follows that Regulation No 2377/90 does not provide for any restrictions when entering substances in Annex II to that regulation.

26. Moreover, Article 4(1) of Directive 96/22, as amended by Directive 2003/74, sets out rules as to what measures Member States are to take in order to prevent misuse when progesterone is administered as a veterinary medicinal product. That provision also expressly provides for progesterone to be administered by injection by a veterinarian. The referring court considers that that provision may be exhaustive in nature in relation to the prevention of misuse of progesterone and thus precludes the adoption of ‘deviating’, stricter rules by a Commission regulation.

27. By order dated 24 October 2006, the Verwaltungsgericht Köln decided to stay the proceedings and to refer the following question to the Court:

‘Is Commission Regulation [No 1873/2003] partially void on account of a breach of higher-ranking Community law (Articles 1(1) and 3 of [Regulation No 2377/90] in conjunction with Article 4(1) of [Directive 96/22]), in so far as application of an injection solution as a pharmaceutical form is excluded by virtue of the note marked (*) against the listing of progesterone in Annex II to [Regulation No 2377/90]?’

28. The Greek and Polish Governments and the Commission submitted written observations. A hearing was requested by cp-Pharma. cp-Pharma, the Greek Government and the Commission presented oral submissions at the hearing on 18 October 2007.

V – Main arguments of the parties

29. The Greek Government and the Commission consider that Regulation No 1873/2003 is compatible with Regulation No 2377/90 and Directive 96/22.

30. The Greek Government submits, that the Court in its judgment in Case C‑198/03 P (13) considered that given that the purpose of Regulation No 2377/90 is to protect public health, the Commission has broad discretion when evaluating pharmacologically active substances and fixing MRLs. Moreover, in Case C‑157/96 (14) the Court held that where there is uncertainty as to the existence or extent of risks to human health, the institutions may take protective measures without having to wait until the reality and seriousness of those risks become fully apparent. It is clear from the recitals in the preamble to Regulation No 1873/2003 that the placing of progesterone in Annex II to Regulation No 2377/90, subject to restrictions concerning its use, were dictated by the necessity to protect public health given the existence of contradictory scientific opinions regarding the possible risks to human health associated with the misuse of that product. In accordance with the ninth and 10th recitals in the preamble to Regulation No 1873/2003, the limitations on the use of progesterone is based on the possibility, foreseen by Regulation No 178/2002, for Community institutions to take into account the results of risk assessment for the purpose of avoiding risks from the misuse of that substance.

31. The Greek Government submits that Article 1(1) of Regulation No 2377/90 is not applicable in the present case as that provision merely defines the framework in accordance with which MRLs are fixed and does not provide for those cases where it is not possible to fix MRLs. That government considers however that a broad interpretation of Article 3 of Regulation No 2377/90 would permit the placing of progesterone, subject to the limitation on its use via the intravaginal route, in Annex II to that regulation given the lack of any existing method for distinguishing naturally produced progesterone and the residues arising as a result of the hormone being administered by man. Given the broad discretion enjoyed by the Commission in this field combined with the terms of Article 15 of Regulation No 2377/90 – which provides that despite the fact that that regulation shall in no way prejudice the application of Community legislation prohibiting the use in livestock farming of certain substances having a hormonal action, it does not exclude the possibility to adopt additional restrictions concerning the use of hormones already dealt with by other Community provisions – the prohibition on the use of progesterone in injectable form is not contrary to Article 4 of Directive 96/22. Moreover, as can be seen from the amendments to Directive 96/22 as a result of the adoption of Directive 2003/74, the use of injectable progesterone was a provisional measure which was applicable up until the evaluation of progesterone within the framework of Regulation No 2377/90 and the fixing of the MRL was carried out.

32. The Commission considers that it had the power pursuant to Article 3 of Regulation No 2377/90, in order to prevent misuse of the substance progesterone, to limit the manner in which that substance may be administered when it placed that substance in Annex II to that regulation. The Commission stresses the complex legislative history which led to the adoption of Regulation No 1873/2003. (15) The Commission submits that the inclusion of a product in Annex II to Regulation No 2377/90 presupposes in general that the control of MRLs is not necessary. In certain cases, however, such as in the case of progesterone, that decision may not be adopted without restrictions in order to ensure that the use of medicinal products in food producing animals is safe.

33. In its judgment in the Boehringer case the Court considered, in substance, that Regulation No 2377/90 does not authorise the Commission to limit the MRL of a veterinary medicinal product to certain therapeutic indications even if such an approach were justified by the requirements inherent in safeguarding public health on which Regulation No 2377/90 is based. While the Commission agrees that it may not impose limitations pursuant to Regulation No 2377/90 concerning therapeutic indications as they have no bearing on the levels of residues in animal tissues, the Commission however considers that Regulation No 1873/2003 does not impose limitations for extrinsic reasons which are unrelated to the quantity of residues in animal tissues. By the adoption of Regulation No 1873/2003, the Commission established a distinction between different forms of administration of progesterone which affect residues. The administration of progesterone by means other than vaginal administration can lead to residues and an increase in the total quantity of progesterone in animal tissues.

34. The Commission considers that in accordance with Article 7(6) of Regulation No 2377/90 it must prepare draft measures taking account of other Community measures. In deciding whether to adopt an MRL or otherwise for progesterone, the Commission had to take into account the fact that it is an active substance capable of protecting animal health. In addition, the Commission had to take account of the limitations on the use of progesterone imposed by Directive 96/22 in order to prevent misuse of that product as a growth promoter. By limiting the authorisation of progesterone to administration via the vaginal route, this guaranteed that progesterone would not be misused and was the only manner to ensure that veterinary medicinal products containing progesterone could be authorised by a Community decision on MRLs without infringing Directive 96/22. If an injectable solution of progesterone were marketed it would be difficult to ascertain whether it was administered in order to promote growth.

35. The Commission emphasises that Article 4(1) of Directive 96/22 empowers the Member States to authorise the administration of progesterone to food-producing animals for therapeutic purposes under certain conditions. That provision does not however provide that the use of progesterone in veterinary medicinal products is always lawful if the conditions laid down therein are met. Indeed, Article 4(1) of Directive 96/22 expressly requires the product to comply with the requirements for placing on the market which in turn requires that the rules relating to MRLs are complied with.

36. The Polish Government considers that Regulation No 1873/2003 violates Regulation No 2377/90 and is thus partially void as the latter regulation does not permit differentiation between different forms of the same pharmaceutical product or the classification of products in the corresponding annexes depending on their form. Moreover, Directive 96/22 clearly permits the administration of progesterone by injection, by a veterinarian. However, with the adoption of Regulation No 1873/2003, progesterone cannot be administered in this form. Poland rejects the Commission claims that the prohibition of the use of progesterone in injectable form acts as an extra guarantee in order to prevent its misuse. The Polish Government considers that that prohibition is totally superfluous as the appropriate restrictions are contained in Directive 96/22 and Regulation No 2377/90. The limits contained in Directive 96/22 concerning the administration of progesterone by injection were established by the Council, in accordance with the procedure laid down by Article 37 EC. Regulation No 1873/2003, by de facto prohibiting the administration of injectable progesterone, impinges on the Council’s power and violates Article 37 EC.

37. The Polish Government also considers that Regulation No 1873/2003 is inadequately reasoned. It should be noted that the Committee recommended that progesterone be inscribed in Annex II to Regulation No 2377/90 without any limitations. In addition to Regulation No 1873/2003 being adopted contrary to the opinion of the Committee, the Polish Government claims that the recitals in the preamble to that regulation give the impression that it was adopted in conformity with the Committee’s opinion. Moreover, the only reason for limiting the use of progesterone given by the Commission in the recitals in the preamble to Regulation No 1873/2003 was to provide an additional safeguard in order to avoid misuse. The Commission however does not explain why it considers that the guarantees provided by Directive 96/22 against the misuse of progesterone are insufficient.

38. Poland submits that Regulation No 1873/2003 is disproportionate in the light of its objective which is to protect public health as the threat to public health is hypothetical in the light of the limitations on the use of injectable progesterone imposed by Directive 96/22. Regulation No 1873/2003 excludes any possibility to market certain veterinary medicines which were used up to its adoption. The effects of Regulation No 1873/2003 were therefore sudden, radical and excessive.

VI – Assessment

39. In the present case the referring court expresses doubts, in the light of the ruling of the Court in the Boehringer case, as to whether the Commission has the power pursuant to Articles 1(1) and 3 of Regulation No 2377/90 when placing progesterone in Annex II to that regulation to impose conditions on the mode of application of that substance. As a supporting argument, the referring Court also considers that the rules contained in Article 4(1) of Directive 96/22, as amended by Directive 2003/74, on the prevention of misuse of progesterone is an exhaustive provision, which precludes the adoption of deviating stricter rules by Commission regulation.

40. In the Boehringer case, the Court examined whether the Commission when fixing the provisional MRL for a veterinary medicinal product, thereby listing it in Annex III to Regulation No 2377/90, can make reference to specific provisions of Directive 96/22 relating to that product. The Court thus examined the legal effect of the inclusion of references to the permitted therapeutic indications for a substance, which mirror those contained in Directive 96/22, when listing that substance in Annex III to Regulation No 2377/90. (16) The administration of the substance in question to farm animals was prohibited in accordance with Article 3 of Directive 96/22. However, in accordance with Article 4 of that directive, Member States may authorise the administration of the substance in question for specific therapeutic purposes which were defined in the directive. (17) In the Boehringer case, the Court found that the references were merely declaratory in nature and intended solely as a reminder that, by virtue of Directive 96/22, the use of the substance in question was prohibited, save for specific therapeutic purposes. The Court therefore considered that the references could not be understood as having the object or effect of laying down a prohibition on the marketing and use of the substance, subject to the therapeutic indications mentioned by them, which is independent of the prohibition laid down by Directive 96/22. (18) The Court also held that the references or reminders in question could not be understood as having the object or effect of placing a limitation on the validity of the MRLs established for the substance in the context of Regulation No 2377/90. (19)

41. In addition to the above findings, at paragraph 55 of its judgment the Court stated that the only limitation on the validity of an MRL envisaged by Regulation No 2377/90 concerns the indication of the limited duration of its validity where the substance in question is entered in Annex III to that regulation. (20) The referring court considers that if that reasoning is applied to a substance in respect of which no MRL has been established and which is included in Annex II to Regulation No 2377/90, it follows that that regulation does not provide for any restrictions when entering substances in Annex II thereto and that Regulation No 1873/2003 is thus partially invalid.

42. Unlike the Court’s finding in the Boehringer case, it is clear from a comparison of the terms of Regulation No 1873/2003 and Directive 96/22, as amended, that the limitations imposed by Regulation No 1873/2003 on the mode of application of progesterone do not merely mirror or recall the terms of Directive 96/22, in particular Articles 3 and 4(1) thereof. Article 3 of Directive 96/22 provisionally prohibits, inter alia, the administering of progesterone to farm animals. Notwithstanding the provisions of Article 3 of Directive 96/22, in accordance with Article 4(1) of that directive, as amended, Member States may authorise, under certain conditions, the administering to farm animals of progesterone by injection or vaginal spirals. Implants of progesterone may not be so authorised. I therefore consider that Regulation No 1873/2003 by limiting the mode of administration of progesterone to intravaginal use effectively departs from the terms of Article 4(1) of Directive 96/22. Moreover, in my view the effects of the limitations on the mode of administration of progesterone imposed by Regulation No 1873/2003 are not merely declaratory in nature but are binding and legislative in character. Indeed the binding nature of the limitations imposed by Regulation No 1873/2003 was confirmed by the agent for the Commission at the hearing on 18 October 2007.

43. The question therefore arises whether the Commission has the competence pursuant to Regulation No 2377/90 to impose binding limitations on the mode of administration of a substance when placing it in Annex II to that regulation and, if so, whether those limitations may be more restrictive than the terms of Article 4(1) of Directive 96/22, as amended, concerning the same substance.

44. It should be noted in that regard that Articles 1(1) and 3 of Regulation No 2377/90 are silent as to whether limitations on the mode of administration may be imposed on substances listed in Annex II thereof and thus, as argued by the Greek Government, do not specifically exclude such limitations. It is therefore necessary, in my view, to examine the scheme and purpose of Regulation No 2377/90 to determine whether such limitations may be imposed.

45. The first recital in the preamble to Regulation No 2377/90 states that the use of veterinary medicinal products in food-producing animals may result in the presence of residues in foodstuffs obtained from treated animals. Such products however play an important role in agricultural production. (21) Regulation No 2377/90 lays down a Community procedure in accordance with which pharmacologically active substances in veterinary medicinal products administered to food-producing animals are assessed with a view to determining whether those substances result in the presence of residues in animal tissues which are harmful to public health and accordingly whether the substances should be placed in Annexes I to IV to that regulation. (22) The Council has delegated the primary task of determining whether such substances should be placed in Annexes I to IV to Regulation No 2377/90 to the Commission, in accordance with the procedure laid down in Article 6 et seq. of that regulation.

46. The categorisation of substances pursuant to Articles 2 to 5 of Regulation No 2377/90 is of considerable importance due, in particular, to the terms of Article 14 thereof which provide in substance that the administration to food-producing animals of veterinary medicinal products containing pharmacologically active substances which are not mentioned in Annexes I, II or III to that regulation is prohibited. Moreover, Article 6(1) of Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products (23) ensures that a veterinary medicinal product may not be the subject of a marketing authorisation for the purpose of administering it to one or more food-producing species unless the pharmacologically active substances which it contains appear in Annexes I, II or III to Regulation No 2377/90. In Monsanto , (24) the Court highlighted the fact that the procedures for establishing MRLs and issuing marketing authorisations are inherently linked, inasmuch as a marketing authorisation will not be issued in respect of a veterinary medicinal product for administration to food-producing animals unless an MRL has been established, and, by the same token, an MRL will not be established for a new pharmacologically active substance unless that substance is intended to be placed on the market. (25)

47. As regards the present case, the Commission outlined in the sixth recital in the preamble to Regulation No 1873/2003 that the SCVPH had repeatedly confirmed that the use of hormones for growth promotion purposes in meat production poses a potential health risk to consumers. In the same recital the Commission also highlighted the fact that there were insufficient data available on progesterone to make a quantitative estimate of the risk arising from the exposure to residues in meat and meat products originating from treated animals. No threshold therefore was defined for progesterone by Regulation No 1873/2003. That substance was placed in Annex II to Regulation No 2377/90, subject to restrictions on its mode of administration, limiting it to intravaginal use to the exclusion, inter alia, of an injectable solution. The 10th recital in the preamble to Regulation No 1873/2003 provides that the restrictions imposed by that regulation on the mode of administration of progesterone to animals of the bovine species are aimed at creating an additional safeguard against the possible misuse of veterinary medicinal products containing progesterone.

48. The Commission explained in considerable detail in its pleadings that, due to the particular characteristics of certain substances, the mode of administration of those substances may have a direct impact on the level of residues in animal tissues. In relation to the substance progesterone the Commission, in response to a written question put to it by the Court, asserted that the mode of administration of progesterone influenced the level of residues of that substance in animal tissues. The Commission stated that where progesterone is administered by vaginal spiral, the quantity of progesterone drops immediately once that preparation is removed from the animal’s body. The Commission also stated that due to the fact that vaginal spirals administer a large dose of progesterone, they are not suitable in practice for growth promotion as the dose administered may detrimentally affect an animal’s health if continued over a period of time. Moreover, vaginal spirals must be changed every seven days and may be easily detected during possible controls. At the hearing the Commission stated that where progesterone is administered by injection, residues of that substance remain in the animal’s body even after administration is terminated. In addition, the Commission stated that there was a risk of misuse of progesterone in injectable form as it can easily be used to administer small doses of progesterone which can stimulate growth.

49. As can seen in particular from the sixth, ninth and 10th recitals in the preamble to Regulation No 1873/2003 and the submissions of the Commission presented to the Court, the Commission has drawn a direct correlation between the mode of administration of progesterone, the misuse of that substance for growth promotion and the presence and quantity of progesterone residues in animal tissues.

50. In contrast, it should be noted that cp-Pharma stated, in response to a written question put to it by the Court, that it could not indicate whether the mode of administration of progesterone had an effect on the quantity of residues without carrying out a study on the residues concerned. Moreover, cp-Pharma indicated that the intravaginal use of progesterone may promote growth if the level of progesterone administered is sufficiently high. The referring court also expresses doubts as to whether the administration of progesterone by intramuscular injection results in residues that require the prohibition of that form of the substance in the interest of public health.

51. It is clear from Commission v CEVA and Pfizer (26) that the Commission, when carrying out its assessment of a pharmacologically active substance for the purpose of fixing a MRL pursuant to the procedure contained in Regulation No 2377/90, enjoys a broad margin of appreciation. In my view, the same margin of appreciation also undoubtedly extends to the Commission’s decision to place a substance in Annex II to Regulation No 2377/90. (27) This is particularly so in a case such as the present where a comparison of the pleadings of the parties, the terms of the preliminary reference and the legislative history leading to the adoption of Regulation No 1873/2003 demonstrate that there is considerable ongoing scientific uncertainty in relation to the effect on public health of progesterone in the tissue of food-producing animals. Indeed, the Court acknowledged in Commission v CEVA and Pfizer that the situation in relation to progesterone was particularly complex due to the fact that it is an endogenous substance and there are presently no reliable means to check abuse of that substance. (28)

52. Pursuant to Article 3 of Regulation No 2377/90, Annex II thereto is reserved for substances in respect of which it is not necessary for the purposes of protecting public health to fix a MRL. In my view, while Articles 1(1) (29) and 3 of Regulation No 2377/90 do not specifically provide for the possibility of imposing conditions on the mode of administration of a particular substance listed in Annex II to that regulation, it cannot be excluded that there may be instances where the Commission’s decision to place a particular substance in Annex II is based on the finding that the substance in question is not apt to be placed in Annexes I, III and IV to Regulation No 2377/90 and that that substance, when administered in a particular manner, does not give rise to residues in animal tissues which are harmful to public health. In such cases, I consider that the Commission will not have exceeded its delegated powers pursuant to Regulation No 2377/90 and acts within the scope of its margin of appreciation where it places the substance in question in Annex II to that regulation and imposes limits on the mode of administration of the substance which are directly aimed at and circumscribed to ensuring that the presence or quantity of residues in animal tissues do not pose a risk to public health. (30) In my view, the possibility for the Commission to impose limitations on the mode of administration of a substance placed in Annex II to Regulation No 2377/90, where those limitations are aimed at ensuring that the presence or quantity of residues of that substance in animal tissues do not pose a risk to public health, is in line with the Community’s precautionary principle. (31)

53. Moreover, I consider that this approach is not at variance with the statement of the Court at paragraph 55 of the Boehringer case which must be interpreted in the context of the specific facts of that case. The Boehringer case concerned limitations placed on a substance relating to certain therapeutic indications rather than the mode of administration of a particular substance. I believe that the circumstances in the Boehringer case may be distinguished from those of the present as, it is arguable that in contrast to the mode of administration of a substance, the effect on public health of residues of a substance in animal tissues is not dependent on the therapeutic indications for which the substance was administered. (32)

54. I would add however an important caveat to the foregoing.

55. In my view, the Commission, notwithstanding its broad margin of appreciation, must, when imposing limitations on the mode of administration of a substance included in Annex II to Regulation No 2377/90, stay within the confines of the legislative power delegated to it by the Council and comply, inter alia, with all the basic elements of that regulation. In that regard, the Court has held that the Commission is authorised to adopt all the implementing measures which are necessary or appropriate for the implementation of the basic legislation, provided that they are not contrary to such legislation or to the implementing legislation adopted by the Council. (33)

56. According to Article 15 of Regulation No 2377/90, that regulation shall in no way prejudice the application of Community legislation prohibiting the use in livestock farming of certain substances having a hormonal action. (34) In my view, any implementing legislation adopted by the Commission pursuant to Regulation No 2377/90 must comply with the clear terms of Article 15 thereof. While Article 15 of Regulation No 2377/90 does not specifically refer to Directive 96/22, I consider that that directive, which seeks, inter alia, to prevent the misuse of certain hormones including progesterone in stockfarming, is covered by the terms of Article 15 of that regulation. The Commission is thus obliged pursuant to Article 15 of Regulation No 2377/90 when categorising a substance in Annexes I to IV to that regulation not to derogate from the terms of Directive 96/22, as amended, including Article 4(1) thereof which forms an integral part of that directive. (35) Given that the provisions of Regulation No 1873/2003 which limit the mode of administration of progesterone to intravaginal use clearly depart from the terms of Article 4(1) of Directive 96/22, I consider that those provisions of Regulation No 1873/2003 are invalid as the Commission has exceeded its implementing powers, as it failed to adhere to one of the basic elements of Regulation No 2377/90, namely Article 15 thereof.

57. Aside from the specific terms of Article 15 of Regulation No 2377/90, I consider that Regulation No 1873/2003 has modified the scope of obligations imposed on the Member States by Directive 96/22, as amended by Directive 2003/74, in that the latter regulation effectively eliminates the possibility hitherto available for the Member States pursuant to Article 4(1) of Directive 96/22 to authorise the administration under certain conditions of progesterone to farm animals. In my view, any modification of the scope of Directive 96/22, as amended, which is not specifically envisaged by that directive must be carried out pursuant to the legislative procedure provided for in Article 152(4)(b) EC. (36) Pursuant to Article 152(4)(b) EC ‘[t]he Council, acting in accordance with the procedure referred to in Article 251 and after consulting the Economic and Social Committee and the Committee of the Regions, shall contribute to the achievement of the objectives referred to in this Article through adopting: … by way of derogation from Article 37 [EC], measures in the veterinary and phytosanitary fields which have as their direct objective the protection of public health’. The legislative procedure in Article 251 EC, which is also referred to as the co-decision procedure, calls inter alia for the participation of the European Parliament, the Council and the Commission in the legislative process. In my view, Regulation No 1873/2003 which was not adopted in accordance with the procedure laid down by Article 251 EC, encroaches on the legislative powers of both the European Parliament and the Council and thus affects the institutional balance intended by the Treaty. I therefore consider that the assertion by the agent for the Commission at the hearing that the participation of the Standing Committee provided for pursuant to Article 8 of Regulation No 2377/90 in the procedure leading to the adoption of Regulation No 1873/2003 ensured that the latter regulation was adopted with the agreement or consent of the Council must be rejected. In my view, aside from the fact that this approach ignores the role of the European Parliament in the legislative procedure provided by Article 251 EC, the Standing Committee referred to in Article 8 of Regulation No 2377/90 cannot act in the place of the Council, where the participation of the Council is specifically required.

58. In that regard, the Commission’s suggestion at point 35 above, (37) that given that Article 4(1) of Directive 96/22 provides that a veterinary medicinal product must comply with the Community rules concerning marketing authorisations (38) which in turn require that the rules relating to MRLs are complied with, the Commission can by the adoption of legislation implementing Regulation No 2377/90 incidentally alter the specific terms of Article 4(1) of Directive 96/22, must be rejected. While a particular substance must be listed in Annexes I to III to Regulation No 2377/90 in order to obtain a marketing authorisation pursuant to Directive 2001/82 and thereby comply with one of the conditions set by Article 4(1) of Directive 96/22 in order for a Member State to authorise its administration to farm animals, the Commission may not through its delegated powers under Regulation No 2377/90 impinge on the specific terms of Article 4(1) of Directive 96/22, which permits Member States, inter alia, to authorise the administration to farm animals of progesterone by injection in certain circumstances, and thereby unlawfully arrogate to itself legislative power which rightly rests with the European Parliament, the Council and the Commission.

59. I therefore consider that Regulation No 1873/2003 is invalid to the extent that it limits the mode of administration of progesterone to ‘intravaginal therapeutic or zootechnical use and in accordance with the provisions of Directive 96/22/EC’ and excludes administration of that substance by injection. In my view, Regulation No 1873/2003 should be declared invalid in its entirety as the limitations imposed by that regulation on the mode of administration of progesterone form a central and thus inextricable part of that regulation as a whole and cannot be severed from the remainder of the regulation. It is evident from the pleadings in this case, the legislative history which preceded the adoption of Regulation No 1873/2003 and the recitals in the preamble to that regulation that the decision of the Commission to place progesterone in Annex II to Regulation No 2377/90 was indissociably linked to limiting the mode of administration of that substance to intravaginal use.

60. I shall also deal with the arguments raised by the Polish Government relating to the inadequacy of reasoning (39) of Regulation No 1873/2003 for the sake of completeness.

61. According to the settled case-law relating to Article 253 EC, the scope of the obligation to state reasons depends on the nature of the measure in question. Where a measure of general application is involved, the statement of reasons may be confined to indicating the general situation which led to its adoption, on the one hand, and the general objectives which it is intended to achieve, on the other. (40) Furthermore, the Court has repeatedly held that, if the contested measure clearly discloses the essential objective pursued by the institution, it would be excessive to require a specific statement of reasons for the various technical choices made. (41)

62. In my view, contrary to the claim of the Polish Government, Regulation No 1873/2003 does not give the impression that it was adopted in conformity with the Committee’s opinion. The seventh recital in the preamble to Regulation No 1873/2003 shows clearly and unequivocally that the Committee recommended that progesterone be placed in Annex II to Regulation No 2377/90. However, the eighth to the 11th recitals in the preamble to Regulation No 1873/2003 clearly indicate why the Commission considered it was necessary to impose limitations on the mode of administration of progesterone, despite its inclusion in Annex II to Regulation No 2377/90. Moreover, contrary to the claims of the Polish Government, the Commission indicated briefly in the recitals in the preamble to Regulation No 1873/2003 why it considered that the guarantees provided by Directive 96/22 against the misuse of progesterone were insufficient. It is clear from the recitals in the preamble to Regulation No 1873/2003, particularly the fifth and the eighth to the 10th recitals, that the purpose of limiting the mode of administration of progesterone to intravaginal use was to provide an additional safeguard, to avoid misuse of that substance, to those already provided by Directive 96/22. In that regard, the Commission specifically indicated in the eighth recital in the preamble to Regulation No 1873/2003 that it considered that the methods available to detect progesterone in animal tissues were incapable of controlling that the restrictions of the use of that substance established in Directive 96/22 are observed. In my view, as the key recitals in the preamble to Regulation No 1873/2003 mentioned above, t ogether with the remaining recitals, contain a coherent and sufficient description of the general situation which led to its adoption, the obligation to state reasons laid down in Article 253 EC has been satisfied.

63. As is clear from the above, I consider that Regulation No 1873/2003 is contrary to Community law and should therefore be declared invalid in its entirety. I consider however that in the light of the particular circumstances of this case, not least the considerable scientific uncertainty surrounding the substance progesterone, the risk of its misuse as a growth promoter and the need to administer that substance to farm animals for therapeutic purposes, all the effects of Regulation No 1873/2003 should be preserved provisionally until the Commission has adopted, within a reasonable period of time, a new regulation on the matter pursuant to Regulation No 2377/90 which complies with Community law. (42)

VII – Conclusion

64. I consider, accordingly, that the Court should answer the question referred by the Verwaltungsgericht Köln (Administrative Court, Cologne) (Germany) as follows:

(1) Commission Regulation (EC) No 1873/2003 of 24 October 2003 amending Annex II to Council Regulation (EEC) No 2377/90 laying down a Community procedure for the establishment of maximum residue limits of veterinary medicinal products in foodstuffs of animal origin is invalid in its entirety;

(2) The effects of Regulation No 1873/2003 shall be preserved for a reasonable period of time until the Commission has adopted a new regulation on the matter pursuant to Council Regulation (EEC) No 2377/90 which complies with Community law.

(1) .

(2) – OJ 2003 L 275, p. 9.

(3) – Regulation of 26 June 1990 laying down a Community procedure for the establishment of maximum residue limits of veterinary medicinal products in foodstuffs of animal origin (OJ 1990 L 224, p. 1).

(4) – OJ 1996 L 125, p. 3.

(5) – Article 3 of Regulation No 2377/90 provides that ‘[w]here, following an evaluation of a pharmacologically active substance used in veterinary medicinal products, it appears that it is not necessary for the protection of public health to establish a maximum residue limit, that substance shall be included in a list in Annex II …’.

(6) – Regulation of 22 July 1993 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Products (OJ 1993 L 214, p. 1).

(7) – Regulation … laying down a Community procedure for the establishment of maximum residue limits of veterinary medicinal products in foodstuffs of animal origin (OJ 1997 L 67, p. 1).

(8) – Directive … concerning the prohibition on the use in stockfarming of certain substances having a hormonal or thyrostatic action and of beta-agonists (OJ 2003 L 262, p. 17).

(9) – Directive 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).

(10) – Regulation of the European Parliament and of the Council of 28 January 2002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety (OJ 2002 L 31, p. 1).

(11) – COM(2001) 627 final.

(12) – [2002] ECR I‑1917, paragraph 55.

(13) – Commission v CEVA and Pfizer [2005] ECR I‑6357, paragraphs 75 and 80.

(14) – National Farmers’ Union and Others [1998] ECR I‑2211, paragraph 63.

(15) – See Commission v CEVA and Pfizer , cited in footnote 13, paragraphs 12 to 32, and point 21 above.

(16) – By its adoption of Commission Regulation (EC) No 1312/96 of 8 July 1996 amending Annex III to Regulation (EEC) No 2377/90 (OJ 1996 L 170, p. 8), the Commission amended Annex III to Regulation No 2377/90 by fixing provisional MRLs for a particular substance and by specifying under its heading ‘Other provisions’, inter alia, the therapeutic indications authorised for that substance.

(17) – See Article 1(2)(b) of Directive 96/22.

(18) – See paragraph 54 of Commission v Boehringer Ingelheim Vetmedica and C. H. Boehringer Sohn (cited in footnote 12).

(19) – See paragraph 55 of Commission v Boehringer Ingelheim Vetmedica and C. H. Boehringer Sohn (cited in footnote 12).

(20) – I would note briefly that the Court’s statement at paragraph 55 of Commission v Boehringer Ingelheim Vetmedica and C. H. Boehringer Sohn (cited in footnote 12) is obiter dictum as the question of whether or not the Commission may impose limitations on a substance listed in Annex III to Regulation No 2377/90 concerning therapeutic indications was not relevant to the Court’s ruling in that case which hinged in fact on the non-legislative character of the references in question.

(21) – See the fourth recital in the preamble to Regulation No 2377/90.

(22) – See point 5 above for an explanation of the reasons for classifying a substance in Annexes I to IV of Regulation No 2377/90.

(23) – OJ 2001 L 311, p. 1.

(24) – C‑2 48/99 P [2002] ECR I‑1.

(25) – See paragraph 80.

(26) – Cited in footnote 13.

(27) – In accordance with the third recital in the preamble to Regulation No 2377/90, MRLs are to be established in accordance with generally recognised principles of safety assessment, taking into account any other scientific assessment of the safety of the substances concerned which may have been undertaken by international organisations. Moreover, the sixth recital in the preamble to Regulation No 2377/90 states that the procedure for the establishment of MRLs at Community level must involve a single scientific assessment of the highest possible quality. In my view, equivalent standards apply when a substance is placed in Annex II to Regulation No 2377/90.

(28) – Cited in footnote 13, paragraph 82.

(29) – Which establishes a definition of the terms ‘residues of veterinary medicinal products’ and ‘maximum residue limit’ (see point 4 above).

(30) – Therefore, limitations may not be imposed on the mode of administration of substances listed in Annex II to Regulation No 2377/90 unless they are directed at ensuring that the presence or quantity of residues in animal tissues do not harm human health.

(31) – For an expression of this principle in the field of public health, see in particular, Articles 3(p) EC, 152(1) EC and 153(1) and (2) EC. It is settled case-law that, in the field of public health, the precautionary principle implies that, where there is uncertainty as to the existence or extent of risks to human health, the institutions may take precautionary measures without having to wait until the reality and seriousness of those risks become fully apparent (Case C‑180/96 United Kingdom v Commission [1998] ECR I‑2265, paragraph 99; National Farmers’ Union and Others , cited in footnote 14, paragraph 63; Case T‑199/96 Bergaderm and Goupil v Commission [1998] ECR II‑2805, paragraph 66; T‑13/99 Pfizer Animal Health v Council [2002] ECR II‑3305, paragraph 139; T‑70/99 Alpharma v Council [2002] ECR II‑3495, paragraph 152). I would note that Article 7(1) of Regulation No 178/2002 is a concrete expression of the precautionary principle in the area of food law.

(32) – See Opinion of Advocate General Ruiz-Jarabo Colomer in Commission v Boehringer Ingelheim Vetmedica and C. H. Boehringer Sohn (cited in footnote 12), point 42. See also paragraph 196 of the judgment in Joined Cases T‑125/96 and T‑152/96 Boehringer Ingelheim Vetmedica and C. H. Boehringer Sohn v Council and Commission [1999] ECR II‑3427 in which the Court of First Instance held that ‘[i]t is self-evident that residues of a pharmacologically active substance which are present in food of animal origin are neither more nor less dangerous for health, at a certain level of concentration, according to whether that substance was administered in respect of a particular therapeutic indication. It follows that the MRLs for a given pharmacologically active substance cannot be determined by reference to the therapeutic properties or indications of that substance, which may be numerous.’

(33) – See in the agricultural sphere, Case 121/83 Zuckerfabrik Franken [1984] ECR 2039, paragraph 13; Case C‑478/93 Netherlands v Commission [1995] ECR I‑3081, paragraph 31; and Case C‑239/01 Germany v Commission [2003] ECR I‑10333, paragraph 55. See also in relation to the Community Customs Code Case C‑48/98 Söhl & Söhlke [1999] ECR I‑7877, paragraph 36.

(34) – See also Article 7(6) of Regulation No 2377/90 pursuant to which the Commission is obliged to prepare draft measures taking account of Community legislation.

(35) – While it is true that Article 4(1) of Directive 96/22 as an exception or derogation to the general rule laid down in Article 3 of that directive, which provisionally prohibits the administering of progesterone to farm animals, must be interpreted strictly – see, to that effect, inter alia, Case C‑83/99 Commission v Spain [2001] ECR I‑445, paragraph 19; Case C‑5/01 Belgium v Commission [2002] ECR I‑11991, paragraph 56; and C‑43/04 Stadt Sundern [2005] ECR I‑4491, paragraph 27 – that provision cannot simply be read out of Directive 96/22 on the basis of its exceptional nature.

(36) – It will be noted that Article 152(4)(b) EC is the legal basis of Directive 2003/74. In his Opinion in Joined Cases C‑453/03, C‑11/04, C‑12/04 and C‑194/04 ABNA and Others [2005] ECR I‑10423, Advocate General Tizzano noted that ‘[p]rior to the Treaty of Amsterdam, measures relating to the common agricultural policy which also pursued the objective of protecting public health had to be adopted, in accordance with the consultation procedure, on the basis of Article 37 EC. … Since the Treaty of Amsterdam entered into force, some of those measures may be based on Article 152 EC …’ See points 4 and 5.

(37) – See also submissions of the Greek Government at point 31 above.

(38) – Article 4(1) of Directive 96/22 makes specific reference to Directive 81/851. Directive 81/851 was repealed by Directive 2001/82. Many of the provisions of Directive 81/851 were recast in Directive 2001/82.

(39) – See point 37 above.

(40) – See, to this effect, Case C‑150/94 United Kingdom v Council [1998] ECR I‑7235, paragraph 25; Case C‑284/94 Spain v Council [1998] ECR I‑7309, paragraph 28; and Case C‑168/98 Luxemburg v Parliament and Council [2000] ECR I‑9131, paragraph 62.

(41) – United Kingdom v Council , cited in footnote 40, paragraph 26; Spain v Council , cited in footnote 40, paragraph 30; and Luxemburg v Parliament and Council , cited in footnote 40, paragraph 62.

(42) – It must be recalled that, according to settled case-law, a judgment of the Court in proceedings for a preliminary ruling declaring a Community act to be invalid takes effect, like a judgment annulling an act, from the date on which the act entered into force. The Court may, however, limit in the judgment itself the temporal effects of a preliminary ruling declaring a Community regulation invalid, where that is justified by overriding considerations. That power is inferred from an interpretation of Articles 230 EC, 231 EC and 234 EC, taken together, the reference for a preliminary ruling on the validity of an act and the action for annulment being the two mechanisms provided by the Treaty for reviewing the legality of legislation. See Case C‑212/94 FMC and Others [1996] ECR I‑389, paragraphs 55 and 56; Case 145/79 Roquette Frères [1980] ECR 2917, paragraphs 51 and 52; Case 41/84 Pinna [1986] ECR 1, paragraph 26; and Joined Cases C‑38/90 and C‑151/90 Lomas and Others [1992] ECR I‑1781, paragraphs 23 and 24.