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JUDGMENT OF THE GENERAL COURT (Seventh Chamber)

11 June 2015 (*)

(Medicinal products for human use — Orphan medicinal products — Marketing authorisation for the medicinal product Cholic Acid FGK (renamed Kolbam) — Therapeutic indications — Market exclusivity — Article 8(1) of Regulation (EC) No 141/2000)

In Case T‑452/14,

Laboratoires CTRS, established in Boulogne-Billancourt (France), represented by K. Bacon, Barrister, M. Utges Manley and M. Vickers, Solicitors,

applicant,

v

European Commission, represented by E. White, P. Mihaylova and A. Sipos, acting as Agents,

defendant,

supported by

ASK Pharmaceuticals GmbH, established in Munich (Germany), represented by M. Ambrosius, lawyer,

intervener,

APPLICATION for annulment in part of Commission Implementing Decision C(2014) 2375 of 4 April 2014 granting, in exceptional circumstances, marketing authorisation under Regulation (EC) No 726/2004 of the European Parliament and of the Council for ‘Cholic Acid FGK — cholic acid’, an orphan medicinal product for human use, as amended by Commission Implementing Decision C(2014) 6508 of 11 September 2014 transferring and amending the marketing authorisation granted in exceptional circumstances by Decision C(2014) 2375 for ‘Kolbam — cholic acid’, an orphan medicinal product for human use, in so far as that decision in substance indicates that that medicinal product is authorised for the therapeutic indications for Orphacol or, in the alternative, for annulment of Article 1 of that decision,

THE GENERAL COURT (Seventh Chamber),

composed of M. van der Woude, President, I. Wiszniewska-Białecka (Rapporteur) and I. Ulloa Rubio, Judges,

Registrar: C. Heeren, Administrator,

having regard to the written procedure and further to the hearing on 4 February 2015,

gives the following

Judgment

 Background to the dispute

1        In July 2007, the applicant, Laboratoires CTRS, became the sponsor of a medicinal product whose active ingredient was cholic acid, which was used for the treatment of two rare liver disorders and which had been designated as an orphan medicinal product by the Commission of the European Communities on 18 December 2002.

2        In order to promote the development of effective treatments for patients affected by rare conditions, the European Parliament and the Council adopted Regulation (EC) No 141/2000 of 16 December 1999 on orphan medicinal products (OJ 2000 L 18, p. 1). That regulation, which entered into force on 22 January 2000, introduces a system of incentives to encourage pharmaceutical companies to invest in research, development and bringing to the market of medicinal products intended for the diagnosis, prevention or treatment of rare conditions (‘orphan medicinal products’).

3        According to recital 8 in the preamble to Regulation No 141/2000, the strongest incentive for industry to invest in the development and marketing of orphan medicinal products is where there is a prospect of obtaining market exclusivity for a certain number of years during which part of the investment might be recovered.

4        In that regard, Article 8 of Regulation No 141/2000 provides that orphan medicinal products for which a marketing authorisation has been granted are to benefit from market exclusivity:

‘1. Where a marketing authorisation in respect of an orphan medicinal product is granted pursuant to Regulation [(EC) 726/2004] or where all the Member States have granted marketing authorisations in accordance with the procedures for mutual recognition laid down in Articles [17 and 18 or in Article 28(4) of Directive 2001/83/EC], and without prejudice to intellectual property law or any other provision of Community law, the Community and the Member States shall not, for a period of 10 years, accept another application for a marketing authorisation, or grant a marketing authorisation or accept an application to extend an existing marketing authorisation, for the same therapeutic indication, in respect of a similar medicinal product.

3. By way of derogation from paragraph 1, and without prejudice to intellectual property law or any other provision of Community law, a marketing authorisation may be granted, for the same therapeutic indication, to a similar medicinal product if:

(c)      the second applicant can establish in the application that the second medicinal product, although similar to the orphan medicinal product already authorised, is safer, more effective or otherwise clinically superior.’

5        On 30 October 2009, the applicant submitted an application for marketing authorisation for the medicinal product referred to in paragraph 1 above under the trade name Orphacol, pursuant to Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (OJ 2004 L 136, p.1), in the version applicable at the material time.

6        By Implementing Decision C(2012) 3306 final of 25 May 2012, the European Commission refused to grant marketing authorisation for ‘Orphacol — Cholic acid’, an orphan medicinal product for human use.

7        By judgment of 4 July 2013 in Laboratoires CTRS v Commission, T‑301/12, ECR, EU:T:2013:346, the Court annulled the decision refusing marketing authorisation.

8        On 12 September 2013, the Commission adopted Implementing Decision C(2013) 5934 final, granting, in exceptional circumstances, marketing authorisation under Regulation No 726/2004 for ‘Orphacol (Cholic Acid)’, an orphan medicinal product for human use.

9        Annex I to Implementing Decision C(2013) 5934 final summarises the characteristics of Orphacol and sets out the two therapeutic indications for which Orphacol was granted marketing authorisation. Orphacol is authorised for the treatment of inborn errors of primary bile acid synthesis due to 3β-hydroxy-Δ5-C27-steroid oxidoreductase deficiency or Δ4-3-oxosteroid-5β-reductase deficiency (‘the Orphacol therapeutic indications’).

10      On 21 March 2012, FGK Representative Service GmbH (‘FGK’) submitted an application for marketing authorisation for a medicinal product, whose active ingredient is also cholic acid and which is also used for the treatment of rare liver disorders, and did so under the trade name Cholic Acid FGK. In support of its application, FGK claimed exceptional circumstances under Article 14(8) of Regulation No 726/2004, contending that it was not possible for it to provide full data on the efficacy and safety of the product under normal conditions of use.

11      The initial application for marketing authorisation for Cholic Acid FGK claimed nine therapeutic indications. At an early stage in the authorisation procedure FGK restricted its application to five therapeutic indications, two of which were similar to the Orphacol indications.

12      Given that marketing authorisation had been granted for Orphacol for the therapeutic indications defined in that authorisation and in view of Article 8(1) of Regulation No 141/2000, FGK sought to rely on the derogation under Article 8(3) of the regulation. FGK submitted a report on the ‘similarity’ between Cholic Acid FGK and Orphacol to the European Medicines Agency (EMA).

13      On 21 November 2013, the Committee for Medicinal Products for Human Use of the EMA (‘the CHMP’) adopted an assessment report in which it stated that 2 of the 5 therapeutic indications for which marketing authorisation was being sought for Cholic Acid FGK were similar to the Orphacol indications. The CHMP concluded that Cholic Acid FGK was not clinically superior to Orphacol as regards those two therapeutic indications and stated that it was against applying the derogation based on clinical superiority for which Article 8(3) of Regulation No 141/2000 provides.

14      In view of the CHMP’s conclusions, FGK limited its marketing authorisation application, withdrawing the two therapeutic indications which were similar to those for Orphacol.

15      On 21 November 2013, the CHMP adopted a positive opinion on the grant of marketing authorisation for Cholic Acid FGK as regards the three remaining therapeutic indications, namely the treatment of inborn errors of primary bile acid synthesis due to sterol-27 hydroxylase deficiency (CTX), 2- (or α-) methylacyl-CoA racemase (AMACR) deficiency or cholesterol 7α-hydroxylase (CYP7A1) deficiency.

16      On 29 November 2013 and 9 January 2014, the applicant wrote to the Chairman of the CHMP to express its concerns regarding the wording of the summary of the CHMP’s opinion on Cholic Acid FGK published on the EMA’s website. It was of the view that the reference to the Orphacol therapeutic indications could lead to the circumvention of its market exclusivity.

17      On 23 January 2014, the CHMP adopted a revised positive opinion on the grant of marketing authorisation for Cholic Acid FGK in respect of the three therapeutic indications set out at paragraph 15 above. A summary of that revised opinion and the related CHMP’s assessment report (‘the assessment report’) were published on the EMA’s website.

18      By letter of 23 January 2014 to the applicant, the Chairman of the CHMP stated that Orphacol’s market exclusivity was not being circumvented by the CHMP’s opinion recommending the grant of marketing authorisation for Cholic Acid FGK in respect of therapeutic indications different from those for which Orphacol had been granted marketing authorisation.

19      On 25 February 2014, the applicant wrote to the Commission setting out its concerns regarding the content of the summary of the CHMP’s revised opinion referring to the Orphacol therapeutic indications. It stated that that content was likely to give rise to circumvention of the market exclusivity attaching to Orphacol if marketing authorisation were granted for Cholic Acid FGK. The Commission replied by e-mail on 3 March 2014. On 5 March 2014, the applicant sent a further letter to the Commission. A meeting took place on 21 March 2014, attended by the applicant and the Commission.

20      On 4 April 2014, the Commission adopted Implementing Decision C(2014) 2375 granting, in exceptional circumstances, marketing authorisation under Regulation No 726/2004 for ‘Cholic Acid FGK — cholic acid’, an orphan medicinal product for human use (‘Decision C(2014) 2375’).

21      Article 1 of Decision C(2014) 2375 states as follows:

‘The marketing authorisation provided for in Article 3 of Regulation No 726/2004 is granted for the orphan medicinal product “Cholic Acid FGK — cholic acid”, the characteristics of which are summarised in Annex I to this Decision. “Cholic Acid FGK — cholic acid” shall be registered in the Community register of medicinal products under number EU/1/13/895.’

22      The summary of product characteristics in Annex I to Decision C(2014) 2375 (‘the SmPC’) indicates, inter alia, that the marketing authorisation is granted for Cholic Acid FGK in respect of the three therapeutic indications set out in paragraph 15 above.

23      On 11 April 2014, the applicant wrote to the Commission concerning the wording of the SmPC. It claimed that the references to the Orphacol therapeutic indications in the SmPC amounted to a circumvention of the market exclusivity attaching to Orphacol.

24      On 28 April 2014, the applicant wrote to the EMA and to the Commission regarding the wording of the SmPC and the assessment report relating to Cholic Acid FGK that were published on the EMA’s website, requesting that the references to the Orphacol therapeutic indications in those documents be deleted or amended.

25      The Commission and the EMA replied to the applicant by e-mail of 19 May 2014 and by letter of 23 May 2014, respectively.

26      On 30 May 2014, the applicant once again wrote to the EMA, which replied to it by letter of 6 June 2014.

27      On 12 August 2014, FGK applied for the transfer of the marketing authorisation for Cholic Acid FGK, renamed Kolbam, to the intervener, ASK Pharmaceuticals GmbH, in accordance with Commission Regulation (EC) No 2141/96 of 7 November 1996 concerning the examination of an application for the transfer of a marketing authorisation for a medicinal product falling within the scope of Council Regulation (EEC) No 2309/93 (OJ 1996 L 286, p. 6).

28      On 11 September 2014, the Commission adopted Implementing Decision C(2014) 6508 transferring and amending the marketing authorisation granted in exceptional circumstances by Decision C(2014) 2375 for ‘Kolbam — cholic acid’, an orphan medicinal product for human use (‘Decision C(2014) 6508’).

29      Article 1 of Decision C(2014) 6508 provides that the marketing authorisation granted to FGK for the medicinal product ‘Kolbam — Cholic Acid’ by Decision C(2014) 2375 is transferred to ASK Pharmaceuticals. Article 2 of that implementing decision states that Annexes I to III to Decision C(2014) 2375 are replaced by Annexes I to III to Decision C(2014) 6508, respectively. The amendment of those annexes entailed replacing, in respect of that medicinal product, the trade name Cholic Acid FGK with the trade name Kolbam.

 Procedure

30      The applicant brought the present action by application lodged at the Registry of the General Court on 17 June 2014.

31      By separate document lodged at the Court Registry on the same day, the applicant made an application for the case to be decided under an expedited procedure, in accordance with Article 76a of the Rules of Procedure of the General Court.

32      By document lodged at the Court Registry on 4 July 2014, the Commission indicated that it did not oppose that application.

33      By decision of 17 July 2014, the General Court (Seventh Chamber) granted that application.

34      The Commission lodged its defence on 31 July 2014.

35      By document lodged at the Court Registry on 11 September 2014, FGK and ASK Pharmaceuticals applied for leave to intervene in support of the form of order sought by the Commission. By document lodged at the Court Registry on 18 September 2014, FGK withdrew its application for leave to intervene.

36      By document lodged at the Court Registry on 26 September 2014, the applicant submitted an application seeking confidential treatment of the application vis-à-vis the applicant for leave to intervene.

37      By order of 16 October 2014, the President of the Seventh Chamber of the General Court granted ASK Pharmaceuticals leave to intervene and removed FGK from the file as an applicant for leave to intervene in the present case. The intervener having raised no objections to the application for confidential treatment, it was provided with a non-confidential version of the application.

38      By way of measures of organisation of procedure pursuant to Article 64 of the Rules of Procedure, the Court put a written question to the parties concerning the consequences, for the present proceedings, of the adoption of Decision C(2014) 6508. The applicant and the Commission replied within the prescribed time-limit. In response to the question put by way of measure of organisation of procedure, the applicant sought leave to adapt its form of order so that its application refers to Decision C(2014) 2375, as amended by Decision C(2014) 6508 (‘the contested decision’). Within the period prescribed, the Commission and the intervener indicated that they did not object to that application.

39      By document lodged at the Court Registry on 7 November 2014, the applicant sought measures of organisation of procedure, requesting that the Court order the Commission to disclose certain documents. Within the period prescribed, the Commission and the intervener requested that the Court reject that application.

40      Upon hearing the report of the Judge-Rapporteur, the Court (Seventh Chamber) decided to open the oral procedure.

41      The parties presented oral argument and replied to the questions put by the Court at the hearing which took place on 4 February 2015.

42      The oral procedure was closed on 26 March 2015.

 Forms of order sought by the parties

43      The applicant claims that the Court should:

–        annul the contested decision in so far as the decision in substance indicates that Kolbam is authorised for the Orphacol therapeutic indications or, in the alternative, annul Article 1 of the contested decision;

–        order the Commission to pay the costs.

44      The Commission, supported by the intervener, contends that the Court should:

–        dismiss the application as unfounded or inadmissible;

–        order the applicant to pay the costs.

 Law

 The applicant’s principal head of claim, whereby it seeks annulment of the contested decision in so far as the decision in substance indicates that Kolbam is authorised for the Orphacol therapeutic indications

45      It is apparent from the application that, by its principal head of claim, the applicant seeks annulment of the contested decision in so far as the references in the SmPC and the assessment report to the efficacy of Kolbam for the Orphacol therapeutic indications lead, in essence, to Kolbam being granted marketing authorisation for those therapeutic indications.

46      The Commission contends that this head of claim is inadmissible. It submits that the SmPC and the assessment report form part of the statement of reasons for the contested decision and an application to delete them, or part of them, is inadmissible, as only the operative part of a decision is capable of producing legal effects. It maintains that the applicant is contesting scientific statements which simply form part of the reasons for which the marketing authorisation in question was granted but that it is not contesting the part of the SmPC identifying the therapeutic indications for which the marketing authorisation was granted. The excision of parts of the SmPC and the assessment report which the applicant seeks would result in a decision which the Commission would not have adopted and those parts are not severable from the remainder of the contested decision.

47      The Court notes that Article 1 of the contested decision provides that a marketing authorisation is granted for the medicinal product Kolbam, the characteristics of which are summarised in Annex I to that decision, and that Annex I consists of the SmPC, section 4.1 of which specifies the therapeutic indications for which Kolbam is authorised. Furthermore, it is not disputed that the SmPC mentions the three therapeutic indications referred to in paragraph 15 above (‘the Kolbam therapeutic indications’), which are not those for which Orphacol was granted marketing authorisation.

48      By its principal head of claim, the applicant does not challenge the operative part of the contested decision whereby the Commission granted marketing authorisation in respect of Kolbam for the latter’s therapeutic indications. The applicant in fact seeks annulment of the references to the efficacy of Kolbam for the Orphacol therapeutic indications in the SmPC and the assessment report.

49      It must thus be held that, by the head of claim in question, the applicant is requesting that the Court annul the contested decision in so far as it contains certain passages from the SmPC and the assessment report.

50      Accordingly, by the head of claim in question, the applicant seeks annulment of certain of the reasons on which the contested decision is based but does not challenge the operative part of that decision.

51      According to the case-law, only the operative part of a decision is capable of producing legal effects and, consequently, of adversely affecting a person’s legal interests, regardless of the grounds on which the decision is based. By contrast, the assessments made in the grounds for a decision are not in themselves capable of forming the subject of an action for annulment and can be subject to review by the European Union judicature only to the extent that, as grounds for an act adversely affecting a person’s interests, they constitute the necessary basis for the operative part of that act (see, to that effect, orders of 28 January 2004 in Netherlands v Commission, C‑164/02, ECR, EU:C:2004:54, paragraph 21, and 30 April 2007 in EnBW Energie Baden-Württemberg v Commission, T‑387/04, ECR, EU:T:2007:117, paragraph 127).

52      As a consequence, the applicant’s principal head of claim must be rejected as inadmissible.

 The applicant’s alternative head of claim, whereby it seeks annulment of Article 1 of the contested decision

 Admissibility

53      The Court observes that the applicant, in requesting, by its alternative head of claim, annulment of Article 1 of the contested decision, in essence seeks annulment of the marketing authorisation granted in that article in respect of Kolbam and thus annulment of the contested decision as a whole.

54      The applicant maintains that the scope of the marketing authorisation granted in Article 1 of the contested decision in respect of Kolbam is broader than that of the Kolbam therapeutic indications because of the references in the SmPC and the assessment report to the efficacy of Kolbam for the Orphacol therapeutic indications. In its submission, as a result of those references, the marketing authorisation in question covers, in essence, the Orphacol therapeutic indications. It submits that the contested decision relies on the SmPC and the assessment report, which form an integral part of the contested decision and must be taken into account in an application for annulment of that decision.

55      The Commission raises the question of admissibility, considering that the claim seeking annulment of Article 1 of the contested decision is only for the case in which the parts of the SmPC and the assessment report that the applicant seeks to have deleted are not severable from the rest of the decision. It further submits that the applicant does not dispute the marketing authorisation for Kolbam for that product’s therapeutic indications but only the alleged overlap between the marketing authorisation for Kolbam and that for Orphacol. As, in its view, there is no such overlap, the Commission contends that the claim seeking annulment of Article 1 of the contested decision is devoid of purpose.

56      In the first place, as regards the question of severability, it should be noted that, even though it is undisputed that the operative part of the contested decision grants Kolbam marketing authorisation for the therapeutic indications identified in the SmPC, which does not expressly mention the Orphacol therapeutic indications, the operative part of a decision must, according to the case-law, be read in the light of the reasons on which it is based (judgments of 22 March 2011 in Altstoff Recycling Austria v Commission, T‑419/03, ECR, EU:T:2011:102, paragraph 152, and 16 September 2013 in Dornbracht v Commission, T‑386/10, ECR, EU:T:2013:450, paragraph 224).

57      According to the case-law, the operative part of an act is indissociably linked to the statement of reasons for it, so that, when it has to be interpreted, account must be taken of the reasons which led to its adoption (see judgment of 30 September 2003 in Cableuropa and Others v Commission, T‑346/02 and T‑347/02, ECR, EU:T:2003:256, paragraph 211 and the case-law cited, and order in EnBW Energie Baden-Württemberg v Commission, paragraph 51 above, EU:T:2007:117, paragraph 127).

58      In the present case, it is thus necessary to consider whether the references in the SmPC and the assessment report to the efficacy of Kolbam for the Orphacol therapeutic indications, which are contested by the applicant, form part of the reasons which led to the contested decision being adopted.

59      Article 1 of the contested decision states that a marketing authorisation is granted to Kolbam, a medicinal product the characteristics of which are summarised in Annex I to the decision. Annex I consists of the SmPC, which, as the Commission acknowledges, is an integral part of the reasons on which the contested decision is based.

60      Moreover, it follows from the case-law that where a decision purely and simply confirms the opinion of the EMA, the content of that opinion, and also that of the assessment report upon which it is based, are an integral part of the statement of reasons for that decision, as regards in particular the scientific assessment of the medicinal product in question (see, to that effect, judgment of 18 December 2003 in Olivieri v Commission and EMEA, T‑326/99, ECR, EU:T:2003:351, paragraph 55).

61      In the present case, the opinion of the CHMP, adopted on 23 January 2014, is based on the assessment report published on the EMA’s website, which contains the CHMP’s scientific assessment of Kolbam. In addition, recital 6 of the contested decision provides that ‘the measures provided for in this Decision are in accordance with the opinion of the [CHMP]’.

62      Consequently, the content of the SmPC and that of the assessment report are an integral part of the statement of reasons for the contested decision and, accordingly, they must be examined in the context of the application for annulment of the contested decision.

63      More specifically, as regards the references to the efficacy of Kolbam for the Orphacol therapeutic indications in the SmPC and the assessment report, the Commission acknowledges that their excision would result in a decision that the Commission would not have adopted and that those references cannot be severed from the contested decision.

64      The applicant’s alternative head of claim, which seeks annulment of Article 1 of the contested decision, including the reasons which provide its necessary support, must therefore be held to be admissible.

65      In the second place, as regards the Commission’s argument that there is no overlap between the marketing authorisation for Kolbam and that for Orphacol, it should be stated that, by that argument, the Commission submits that, since the marketing authorisation for Kolbam does not extend to the Orphacol therapeutic indications, the action is without purpose. It is sufficient to observe, first, that the applicant does not base its claim for annulment on the existence of any such overlap and, secondly, that it is apparent from what has been stated above, that the reasons on which the contested decision is based, which are challenged by the applicant, are an integral part of the decision. The Commission is therefore incorrect when it maintains that the action is without purpose.

 Substance

66      In support of its action, the applicant raises a single plea in law, alleging infringement of Article 8(1) of Regulation No 141/2000. It maintains, in essence, that the contested decision undermines the 10-year period of market exclusivity from which Orphacol benefits on the basis of that provision.

67      According to the Commission, since, formally, the marketing authorisation for Kolbam was not granted for the Orphacol therapeutic indications, there can be no breach of Orphacol’s market exclusivity for those therapeutic indications. Similarly, the intervener submits that only the therapeutic indications mentioned in section 4.1 of the SmPC are covered by the marketing authorisation in question and that, since the information in section 5.1 of the SmPC cannot be understood as an authorisation for the medical conditions mentioned therein, there can be no breach of market exclusivity.

68      In that regard, the Court notes that the therapeutic indications for which Kolbam was authorised are specifically defined in section 4.1 of the SmPC. The applicant does not deny that Kolbam’s marketing authorisation concerns only the therapeutic indications defined in that section and, formally, does not relate to the same therapeutic indications as those for which Orphacol was authorised.

69      However, according to the applicant, the references, in the SmPC and the assessment report concerning Kolbam, to the efficacy and safety of cholic acid in treating the Orphacol therapeutic indications amount, in substance, to a statement that Kolbam is effective for treating the Orphacol therapeutic indications, implying that Kolbam is also authorised for those indications. The applicant submits that this results in the circumvention of the market exclusivity from which Orphacol benefits under Article 8(1) of Regulation No 141/2000.

70      As the applicant made clear at the hearing, it does not dispute all the references to the Orphacol therapeutic indications in the SmPC and the assessment report but only the statements concerning the efficacy of Kolbam for the Orphacol therapeutic indications.

71      Thus, so far as the assessment report is concerned, the applicant disputes the following passages:

‘[T]he CHMP considered that observed consistency of the results and the maintenance of improvement in patients’ symptoms provides enough evidence of the therapeutic efficacy of [cholic acid] in the treatment of patients with inborn errors of bile acid synthesis due to 3β-HSD, Δ43-oxoR [the Orphacol therapeutic indications], CTX, AMACR and CYP7A1 deficiencies [the Kolbam therapeutic indications]’ (section 2.5.3 of the assessment report, relating to the discussion on clinical efficacy) and ‘[Cholic acid] is an effective treatment for the indication of inborn errors of the synthesis of primary bile acids. Overall, the CHMP is able to conclude that [Kolbam] has therapeutic efficacy in the treatment of patients with 3β-HSD, Δ43-oxoR [the Orphacol therapeutic indications], CTX, AMACR and CYP7A1 deficiencies [the Kolbam therapeutic indications]’ (section 2.5.4 of the assessment report, relating to the conclusion on clinical efficacy).

72      So far as the SmPC is concerned, the applicant submits that section 5.1 thereof, which relates to ‘pharmacodynamic properties’, mentions, in the part relating to ‘pharmacodynamic effects’, amongst the enzyme defects concerned, deficiencies corresponding to the Orphacol therapeutic indications and, in the part relating to ‘clinical efficacy and safety’, the references to the results of clinical studies in respect of patients presenting with deficiencies corresponding to the Orphacol therapeutic indications. It disputes the conclusion of the part of the SMPC relating to ‘clinical efficacy and safety’, which indicates that ‘[t]he results confirmed that oral [cholic acid] treatment can down-regulate the synthesis of atypical bile acids and provide an effective short- as well as long-term therapy for patients with inborn errors of bile acid synthesis’. It takes the view that the SmPC thus states directly that Kolbam can be used to treat ‘inborn errors of bile acid synthesis’ in general, a statement which must be understood as including the medical conditions relating to the Orphacol therapeutic indications.

73      The applicant further argues that advertising for Kolbam which mentions its efficacy for all inborn primary bile acid synthesis would comply with the particulars given in the SmPC and would thus not be contrary to Article 87 of Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use (OJ 2001 L 311, p. 67), as interpreted by the Court of Justice in its judgment of 5 May 2011 in Novo Nordisk (C‑249/09, ECR, EU:C:2011:272). However, such advertising would facilitate circumvention of the market exclusivity conferred on Orphacol.

74      Finally, the applicant submits that such circumvention of the market exclusivity attaching to Orphacol also results from the fact that the presence in the SmPC and the assessment report of statements concerning the efficacy of Kolbam for the Orphacol therapeutic indications could lead doctors to prescribe Kolbam for therapeutic indications other than those for which it has been authorised.

75      As a preliminary point, it must be observed that, by virtue of the market exclusivity provided for by Article 8(1) of Regulation No 141/2000, the Commission, for a period of 10 years, may not accept another application for a marketing authorisation, or grant a marketing authorisation or accept an application to extend an existing marketing authorisation, for the same therapeutic indication, in respect of a similar medicinal product.

76      The purpose of the market exclusivity provided for by Article 8(1) of Regulation No 141/2000 is explained in recitals 1, 8 and 9 of the preamble to the regulation, which state:

‘(1)      [S]ome conditions occur so infrequently that the cost of developing and bringing to the market a medicinal product to diagnose, prevent or treat the condition would not be recovered by the expected sales of the medicinal product; the pharmaceutical industry would be unwilling to develop the medicinal product under normal market conditions; these medicinal products are called “orphan”;

(8)      experience in the United States of America and Japan shows that the strongest incentive for industry to invest in the development and marketing of orphan medicinal products is where there is a prospect of obtaining market exclusivity for a certain number of years during which part of the investment might be recovered; …

(9)      sponsors of orphan medicinal products designated under this Regulation should be entitled to the full benefit of any incentives granted by the Community or by the Member States to support the research and development of medicinal products for the diagnosis, prevention or treatment of such conditions, including rare diseases.’

77      As the Commission points out in the defence, the market exclusivity provided for by Article 8(1) of Regulation No 141/2000 is the most significant incentive under the regulation to which an authorised orphan medicinal product is entitled.

78      It must be held that if the effectiveness of Article 8(1) of Regulation No 141/2000 is to be ensured, the off-label prescribing of a medicinal product for therapeutic indications covered by the market exclusivity attaching to another medicinal product by virtue of that provision should not be facilitated.

79      Such a consideration is particularly compelling given that off-label prescribing is not prohibited, or even regulated, by EU law. There is no provision which prevents doctors from prescribing a medicinal product for therapeutic indications other than those for which a marketing authorisation has been granted.

80      Thus, in order to ensure the effectiveness of Article 8(1) of Regulation No 141/2000, the Commission must satisfy itself that a marketing authorisation for a medicinal product is not formulated in such a way that it may induce a prescribing physician to prescribe a medicinal product for therapeutic indications other than those which are covered by that marketing authorisation and for which a marketing authorisation has already been granted for another medicinal product that benefits from the market exclusivity provided for by the regulation.

81      That would be the case of a marketing authorisation for a medicinal product in which it was stated that a product was effective for therapeutic indications for which a marketing authorisation had already been granted in respect of another orphan medicinal product. Indeed, such statements could tend to facilitate the prescription of the first medicinal product for the therapeutic indications of the second product, which benefits from the market exclusivity provided for by Article 8(1) of Regulation No 141/2000. That would amount to circumvention of the market exclusivity guaranteed by that provision.

82      The point must also be made that off-label prescribing is the sole responsibility of the prescribing physician (see, to that effect, judgment of 11 April 2013 in Novartis Pharma, C‑535/11, ECR, EU:C:2013:226, paragraph 48). That responsibility could in practice be attenuated by the presence, in a medicinal product’s marketing authorisation, of statements that the product is effective and safe for treating other therapeutic indications than those for which its marketing authorisation has been granted.

83      Furthermore, as regards the applicant’s argument concerning the fact that circumvention of the market exclusivity attaching to Orphacol could be facilitated by advertising for Kolbam referring to its efficacy for all inborn errors of primary bile acid synthesis, the Commission submits that the application of Article 87 of Directive 2001/83, as interpreted by the Court of Justice in Novo Nordisk, paragraph 73 above (EU:C:2011:272), prevents the advertising of a medicinal product from promoting usages outside the approved therapeutic indications.

84      In that regard, it is to be noted that Article 87(2) of Directive 2001/83 provides that all parts of the advertising of a medicinal product must comply with the particulars listed in the summary of product characteristics.

85      The Court of Justice, in Novo Nordisk, paragraph 73 above, (EU:C:2011:272, paragraph 42), held that no part of an advertisement for medicinal products may ever suggest, inter alia, therapeutic indications, pharmacological properties, or other characteristics that conflict with the summary of the product characteristics approved by the competent authorities upon granting marketing authorisation for that medicinal product.

86      The Court also held that Article 87(2) of Directive 2001/83 cannot be interpreted as requiring that all claims in advertisements for medicinal products directed at persons qualified to prescribe or supply them have to be included in that summary of product characteristics or be derivable from information in that summary. Indeed, such an interpretation would render Article 91(1) and Article 92 of that directive meaningless, since those provisions authorise the publication of supplementary information in advertisements directed at health professionals, provided that it is compatible with the summary (judgment in Novo Nordisk, paragraph 73 above, EU:C:2011:272, paragraph 48).

87      Thus, the Court of Justice took the view that Article 87(2) of Directive 2001/93 requires only that the information in the advertising of a medicinal product comply with the summary (judgment in Novo Nordisk, paragraph 73 above, EU:C:2011:272, paragraph 43).

88      It follows that — as the Commission maintains — Article 87(2) of Directive 2001/83 does indeed prohibit any statement in advertising for Kolbam that the latter is authorised for therapeutic indications other than those for which it has been approved. However, Article 87(2) does not preclude advertising which, in keeping with the SmPC, makes statements as to the efficacy of Kolbam for treating inborn errors of primary bile acid synthesis.

89      In view of those matters, it is appropriate to consider whether the references in the SmPC and the assessment report which the applicant challenges are liable to give rise to circumvention of the market exclusivity attaching to Orphacol.

90      In that regard, it must be recalled that the SmPC and the assessment report form part of the statement of reasons on which the contested decision is based. The operative part of that decision must be read in the light of the reasons which underpin it — in other words, the marketing authorisation for Kolbam in Article 1 of the decision must be read in the light of the content of the SmPC and the assessment report.

91      As regards the assessment report, the applicant argues that it contains explicit references to the efficacy of Kolbam for the Orphacol therapeutic indications; that is not disputed by the Commission.

92      As regards the SmPC, the applicant disputes the statement, in the part relating to the clinical efficacy and safety of Kolbam, concerning the efficacy of cholic acid for all inborn errors of primary bile acid synthesis, following the results of clinical studies in respect of, inter alia, patients with conditions corresponding to the Orphacol therapeutic indications.

93      As the Commission acknowledges, the summary of product characteristics is an important tool for prescribing physicians, which allows them access to the scientific rationale and evidence in support of the therapeutic indications for which the medicinal product concerned has been authorised.

94      It must be observed that the information intended for the prescribing physician which is set out in the summary of product characteristics is not limited to the therapeutic indications defined in section 4.1 thereof, but is found throughout that summary, in particular in the part relating to the clinical efficacy and safety of the medicinal product concerned. The SmPC must therefore be held to contain information which indicates that the efficacy of Kolbam extends beyond the therapeutic indications for which it was authorised.

95      Accordingly, the SmPC and the assessment report contain information which, it is true, does not formally alter the scope of the marketing authorisation for Kolbam inasmuch as the therapeutic indications for which Kolbam was authorised are exhaustively listed in section 4.1 of the SmPC. However, in so far as those documents state that Kolbam is effective and safe for therapeutic indications other than those for which it was authorised, namely those for which Orphacol was authorised, it must be held that they contain information, intended for the prescribing physician, which is liable to facilitate the off-label prescribing of Kolbam for the Orphacol therapeutic indications.

96      Given that Orphacol benefits from market exclusivity for the therapeutic indications for which its marketing authorisation was granted, it must be held that that information is, in practice, liable to give rise to circumvention of that market exclusivity.

97      It follows that the statements relating to the efficacy of Kolbam for the Orphacol therapeutic indications, which are found in the SmPC and the assessment report, are liable to render Article 8(1) of Regulation No 141/2000 ineffective and to undermine the market exclusivity which Orphacol enjoys under that provision.

98      That conclusion is not called into question by the Commission’s arguments seeking to justify the statements challenged by the applicant which relate to the efficacy of Kolbam for the Orphacol therapeutic indications and are made in the assessment report and the SmPC.

99      As regards, in the first place, the assessment report, the Commission submits, firstly, that the statements that the applicant challenges, which are set out in paragraph 71 above, have a scientific rationale and refer to the clinical studies submitted by FGK concerning the assessment of Kolbam. It argues that, in view of the limited number of patients, the results of the clinical studies across all enzymatic defects had to be considered for the purpose of the scientific assessment regarding the efficacy of Kolbam. It maintains that, given that the majority of the data concerned patients with the Orphacol therapeutic indications, it was essential to draw conclusions in respect of those therapeutic indications in order to reach a conclusion in respect of the therapeutic indications covered in Kolbam’s application for marketing authorisation. It submits that references to the efficacy of Kolbam for the Orphacol therapeutic indications are necessary for a transparent and complete presentation of the scientific assessment that led to the positive opinion of the CHMP.

100    It must be observed that, although the Commission’s arguments are capable of justifying a complete presentation of the clinical results for Kolbam in the assessment report, they do not establish that it is necessary to include in the grounds for the contested decision statements concerning the efficacy of Kolbam for therapeutic indications which were not the subject of the application for marketing authorisation for that product.

101    In that regard, the applicant and the intervener stated at the hearing that, within the inborn errors of primary bile acid synthesis, the Kolbam therapeutic indications and the Orphacol therapeutic indications correspond to different diseases.

102    Since Kolbam and Orphacol are different medicinal products, authorised for different therapeutic indications which correspond to different diseases afflicting different patients, the Commission cannot maintain that the statement as to the efficacy of Kolbam for the Orphacol therapeutic indications was necessary for the purposes of the grant of marketing authorisation to Kolbam for the latter’s therapeutic indications.

103    Secondly, the Commission maintains that there is no provision of EU law which prevents the EMA, when drawing up its assessment report, from mentioning conditions that correspond to therapeutic indications for which a medicinal product has received marketing authorisation under Article 8(1) of Regulation No 141/2000. It submits that, on the contrary, assessment reports must fully and faithfully reflect the relevant scientific information. It refers in that regard to the judgment of 26 November 2002 in Artegodan and Others v Commission (T‑74/00, T‑76/00, T‑83/00 to T‑85/00, T‑132/00, T‑137/00 and T‑141/00, ECR, EU:T:2002:283, paragraph 200), which stated, in relation to the Committee for Proprietary Medicinal Products (CPMP), that that committee is obliged to refer, in its opinion, to the main reports and scientific expert opinions on which it relies and to explain, in the event of a significant discrepancy, the reasons why it has departed from the conclusions of the reports or expert opinions supplied by the undertakings concerned and that that obligation is particularly strict in cases of scientific uncertainty.

104    It should be recalled that, initially, the application for marketing authorisation for Kolbam related both to its therapeutic indications and to the Orphacol therapeutic indications and that, following the grant of the marketing authorisation for Orphacol and the conclusions of the CHMP concerning the fact that Kolbam was not clinically superior for the Orphacol therapeutic indications, FGK limited its application for marketing authorisation for Kolbam by no longer referring to the Orphacol therapeutic indications. It was only because of that limitation that Kolbam was regarded as no longer being similar to Orphacol within the meaning of Article 8(1) of Regulation No 141/2000 and that it was possible to examine the application for marketing authorisation for Kolbam. The chronology of the authorisation procedure thus explains the reasons why the clinical studies submitted by FGK in support of the application for marketing authorisation for Kolbam related both to the Kolbam therapeutic indications and to the Orphacol therapeutic indications.

105    The applicant does not challenge the presentation, in the assessment report, of the clinical studies carried out by FGK and does not object to the reference to the reports and expert opinions on which the CHMP relied; it challenges only the statements relating to the efficacy of Kolbam for the Orphacol therapeutic indications.

106    The applicant maintains in essence that, following the grant of the marketing authorisation for Orphacol, Kolbam could not, by virtue of Article 8(1) of Regulation No 141/2000, be the subject of a marketing authorisation for the Orphacol therapeutic indications and that the statement in the assessment report for Kolbam concerning the latter’s efficacy for the Orphacol therapeutic indications was thus unjustified.

107    Accordingly, the Commission’s argument should be rejected in that it seeks to justify only the presence of relevant scientific information in the assessment report.

108    It follows from the foregoing that the Commission has provided no justification for the presence, in the assessment report, of the statements, challenged by the applicant, concerning the efficacy of Kolbam for the Orphacol therapeutic indications.

109    In the second place, as regards the SmPC, the Commission submits, firstly, that the part of the SmPC relating to ‘pharmacodynamic effects’ contains general, publicly-known information about the active substance cholic acid, which complies with the Guideline on Summary of Product Characteristics adopted by the Commission in September 2009 (‘the Guideline’). As to the information on the clinical studies concerning the Orphacol therapeutic indications, it submits that that information was essential for the prescribing physician to understand the reasoning and the evidence supporting the CHMP’s conclusion on the approved therapeutic indications, since the data on the Orphacol therapeutic indications were necessary in order to draw conclusions on the approved therapeutic indications. The Commission adds that the information on the clinical studies concerning the Orphacol therapeutic indications is in accordance with the Guideline, which states that the relevant studies supporting the authorised therapeutic indications should be reflected in the summary of product characteristics.

110    In this regard it must be observed that the applicant does not challenge the presentation of the clinical studies in the SmPC but rather the conclusion on the efficacy of Kolbam for all inborn errors of primary bile acid synthesis, which include the Orphacol therapeutic indications.

111    According to Article 1 of the contested decision, marketing authorisation is granted for Kolbam, for all its characteristics as they are set out in Annex I to the decision, which contains the SmPC.

112    The Guideline states that the summary of product characteristics forms an intrinsic part of the marketing authorisation and that it is the basis of information for healthcare professionals on how to use the medicinal product safely and effectively. It specifies that it is not in the ‘remit’ of the summary to give general advice on the treatment of particular medical conditions. According to the Guideline, the summary provides information on a particular medicinal product and should not include reference to other medicinal products.

113    The Guideline provides, as regards the part of the summary of product characteristics relating to ‘pharmacological properties’, that ‘[s]ections 5.1 to 5.3 should normally mention information, which is relevant to the prescriber and to other health-care professionals, taking into account the approved therapeutic indication(s) and the potential adverse drug reactions’.

114    Furthermore, the part of the Guideline concerning section 5.1 of the summary of product characteristics, which relates to ‘pharmacodynamic properties’, states:

‘It may be appropriate to provide limited information, relevant to the prescriber, such as the main results (statistically compelling and clinically relevant) regarding pre-specified end points or clinical outcomes in the major trials, and giving the main characteristics of the patient population. Such information on clinical trials should be concise, clear, relevant and balanced, and should summarise evidence from relevant studies supporting the indication. …’

115    It is apparent from the Guideline that the role of the summary of product characteristics is to define the medicinal product as approved, that is to say, for the approved therapeutic indications, and that it must contain information on the relevant studies which support the therapeutic indication. In addition, it states that the summary must contain information that is relevant to the prescribing physician. Accordingly, statements relating to the efficacy of the medicinal product concerned for therapeutic indications other than those approved does not form part of the information required by the Guideline.

116    That interpretation is particularly compelling where, as in the present case, those other therapeutic indications could not be the subject of Kolbam’s application for a marketing authorisation because they were already the subject of a marketing authorisation for another medicinal product benefiting from the market exclusivity provided for by Article 8(1) of Regulation No 141/2000.

117    In the present case, the conclusion in the SmPC relating to the efficacy of Kolbam for all inborn errors of primary bile acid synthesis, including the Orphacol therapeutic indications, cannot be considered to be information supporting the therapeutic indications for which Kolbam was authorised. Furthermore, considering that such a statement is relevant to the prescribing physician is liable to facilitate the off-label prescribing of Kolbam for the Orphacol therapeutic indications.

118    The applicant also refers to a document produced by the EMA relating to the presentation of a summary of product characteristics, according to which the aim of that summary is to provide information relevant to prescribing physicians on the therapeutic indications for which a medicinal product has been authorised.

119    That document provides, inter alia, that ‘[section 5.1 of the summary of product characteristics] should provide clear and concise information relevant to healthcare professionals regarding the approved therapeutic indication(s), specific clinical safety data, as well as relevant clinical data in special population(s) (e.g. children or elderly)’.

120    The Commission nevertheless takes the view that that document shows that the statements which the applicant challenges as regards section 5.1 of the SmPC are relevant to prescribing physicians and support the therapeutic indications for which Kolbam was authorised, since they are a factual summary of clinical study data submitted by FGK and analysed by the CHMP.

121    The point should once again be made that the Commission’s arguments seek to justify the presentation in the SmPC of the clinical studies submitted by FGK, even though the applicant does not challenge that presentation. However, those arguments do not establish that it was necessary to include in the SmPC a conclusion concerning the efficacy of Kolbam for therapeutic indications which cannot be the subject of its marketing authorisation.

122    It can be seen from the foregoing that the Commission does not cite any extract from the Guideline that is capable of justifying the inclusion of a conclusion in the SmPC concerning the efficacy of Kolbam for therapeutic indications other than those for which its marketing authorisation was granted.

123    Secondly, the Commission maintains that omitting the information relating to the clinical studies from the SmPC would be an infringement of Article 28(1) of Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004 (OJ 2006 L 378, p. 1).

124    Article 28(1) of Regulation No 1901/2006 provides:

‘Applications may be submitted in accordance with the procedure laid down in Articles 5 to 15 of Regulation (EC) No 726/2004 for a marketing authorisation as referred to in Article 7(1) of this Regulation which includes one or more paediatric indications on the basis of studies conducted in compliance with an agreed paediatric investigation plan.

Where authorisation is granted, the results of all those studies shall be included in the summary of product characteristics and, if appropriate, in the package leaflet of the medicinal product, provided that the competent authority deems the information to be of use to patients, whether or not all the paediatric indications concerned were approved by the competent authority.’

125    As the applicant observed at the hearing, that provision requires only that the SmPC contains information that is of use to patients. Since it has already been stated that the Orphacol therapeutic indications and the Kolbam therapeutic indications concern different diseases and thus different patients, that provision does not justify including a conclusion on the efficacy of Kolbam for the Orphacol therapeutic indications.

126    A presentation in the SmPC of the results of the clinical studies submitted by FGK concerning Kolbam does not necessarily require a conclusion to be drawn on the efficacy of that product for therapeutic indications for which not only has Kolbam not been authorised, but, what is more, for which another medicinal product has been granted marketing authorisation, namely Orphacol, which enjoys market exclusivity.

127    It should be recalled that the applicant does not maintain that the full studies may not be presented in the SmPC; it challenges only the conclusion relating to the efficacy of Kolbam for all inborn errors of primary bile acid synthesis, in particular for the Orphacol therapeutic indications.

128    Thirdly, the Commission argues that the conclusion of the part of the SmPC relating to ‘clinical efficacy and safety’, which is challenged by the applicant, is presented as a general description of the medical condition, which is important for healthcare professionals, and contains public information on the substance cholic acid which is unrelated to Kolbam.

129    In this regard, it is sufficient to note that, even if the information in the SmPC is general in nature and relates to cholic acid, the Commission is incorrect in maintaining that it is unrelated to Kolbam. As has already been stated, the SmPC contains the description of Kolbam, it forms an intrinsic part of the marketing authorisation for Kolbam and describes only the latter’s characteristics.

130    Finally, the Commission contends that the applicant’s argument that certain objective scientific information needs to be deleted from the SmPC and the assessment report would lead to the monopolisation of scientific data that are linked to Orphacol.

131    It should once again be recalled that the applicant does not object to the presence of objective scientific data in the SmPC and the assessment report, but only to the statements relating to the efficacy of Kolbam for the Orphacol therapeutic indications.

132    Furthermore, the application for marketing authorisation for Kolbam was not based on scientific data relating to Orphacol, but on clinical studies carried out by FGK on the basis of FGK’s own clinical data.

133    It is apparent from the foregoing that the Commission has not provided justification for the presence in the SmPC of the statements, challenged by the applicant, relating to the efficacy of Kolbam for all inborn errors of primary bile acid synthesis, including the Orphacol therapeutic indications.

134    Accordingly, the statements concerning the efficacy of Kolbam for the Orphacol therapeutic indications or for all inborn errors of primary bile acid synthesis, which are included in the SmPC and the assessment report, are liable to facilitate the off-label prescribing of Kolbam for the Orphacol therapeutic indications and thus to give rise to circumvention of the market exclusivity attaching to Orphacol and, consequently, to render Article 8(1) of Regulation No 141/2000 ineffective.

135    It follows from all the foregoing that the single plea in law, concerning an infringement of Article 8(1) of Regulation No 141/2000, must be accepted and that, accordingly, the contested decision must be annulled, there being no need to rule on the applicant’s request for a measure of organisation of procedure, whereby it seeks an order for the disclosure of documents.

 Costs

136    Under Article 87(2) of the Rules of Procedure, the unsuccessful party is to be ordered to pay the costs if they have been applied for in the successful party’s pleadings. Since the Commission has been unsuccessful, it must be ordered to pay the applicant’s costs, in accordance with the form of order sought by the latter.

137    Under the third subparagraph of Article 87(4) of the Rules of Procedure, the Court may order an intervener to bear its own costs. In the present case, ASK Pharmaceuticals, which has intervened in support of the Commission, is to bear its own costs.

On those grounds,

THE GENERAL COURT (Seventh Chamber)

hereby:

1.      Annuls Commission Implementing Decision C(2014) 2375 of 4 April 2014 granting, in exceptional circumstances, marketing authorisation under Regulation (EC) No 726/2004 of the European Parliament and of the Council for ‘Cholic Acid FGK — cholic acid’, an orphan medicinal product for human use, as amended by Commission Implementing Decision C(2014) 6508 of 11 September 2014 transferring and amending the marketing authorisation granted in exceptional circumstances by Decision C(2014) 2375 for ‘Kolbam — cholic acid’, an orphan medicinal product for human use;

2.      Orders the European Commission to bear its own costs and to pay those of Laboratoires CTRS;

3.      Orders ASK Pharmaceuticals GmbH to bear its own costs.

Van der Woude

Wiszniewska-Białecka

Ulloa Rubio

Delivered in open court in Luxembourg on 11 June 2015.

[Signatures]


* Language of the case: English.