Bristol-Myers Squibb Pharma v Commission and EMA (Public health - Orphan medicinal products - Judgment) [2018] EUECJ T-329/16 (05 December 2018)

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(Medicinal products for human use — Orphan medicinal products — Decision withdrawing the designation of Elotuzumab as an orphan medicinal product — Decision that the designation criteria were no longer met — Marketing authorisation for the medicinal product for human use Empliciti (Elotuzumab) — Article 5(1)2(b) of Regulation (EC) No 141/2000 — Article 5(8) of Regulation No 141/2000 — Obligation to state reasons)

Bristol-Myers Squibb Pharma EEIG, established in Uxbridge (United Kingdom), represented by P. Bogaert and B. Van Vooren, lawyers, and B. Kelly, Solicitor,

European Commission, represented by A. Sipos and K. Petersen, acting as Agents,

European Medicines Agency (EMA), represented by N. Rampal Olmedo, M. Tovar Gomis, T. Jabłoński and S. Drosos, acting as Agents,

APPLICATION pursuant to Article 263 TFEU for annulment of an act adopted by the Commission removing Elotuzumab from the Community Register of orphan medicinal products for human use and/or of a possible act adopted by the Commission or the EMA determining that Elotuzumab no longer met the criteria for designation as an orphan medicinal product when the marketing authorisation was granted for the medicinal product Empliciti (Elotuzumab) under Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products (OJ 2000 L 18, p. 1),

composed of M. Prek, President, F. Schalin and M.J. Costeira (Rapporteur), Judges,

having regard to the written part of the procedure and further to the hearing on 29 May 2018,

1 On 17 May 2012, the applicant, Bristol-Myers Squibb Pharma EEIG, submitted to the European Medicines Agency (EMA) an application for the designation of Elotuzumab as an orphan medicinal product indicated for the treatment of multiple myeloma. Multiple myeloma is a serious bone marrow cancer.

2 By implementing decision of the European Commission of 9 August 2012, the applicant obtained the designation of the medicinal product Elotuzumab as an orphan medicinal product under Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products (OJ 2000 L 18, p. 1). That designation was based on a favourable opinion issued on 11 July 2012 by the Committee for Orphan Medicinal Products of the EMA (‘COMP’), which found that Elotuzumab fulfilled the criteria for designation as an orphan medicinal product in accordance with Article 3 of that regulation.

3 On 3 July 2015, the applicant submitted to the EMA an application for marketing authorisation (‘MA’) for the medicinal product Empliciti (Elotuzumab) 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).

4 Pursuant to Section B.2.1 of the Communication from the Commission of 29 July 2003 on Regulation No 141/2000 (OJ 2003 C 178, p. 2, ‘the 2003 Communication from the Commission’), the applicant included in its application the information that Elotuzumab had been designated as an orphan medicinal product. It also submitted a report on the criteria on which the orphan designation of the medicinal product was based.

5 On 22 December 2015, the applicant submitted an updated report, indicating that, on 19 November 2015, the Commission had granted an MA for Kyprolis (Carfilzomib), a new medicinal product for the treatment of multiple myeloma, the active ingredient of which is Carfilzomib. Having received the updated report, the COMP asked the applicant to provide further details of significant benefit, in particular by comparison with Carfilzomib. The applicant submitted its response on 1 February 2016, which included, inter alia, a scientific discussion on the significant benefit of Elotuzumab as compared with Carfilzomib.

6 On 28 January 2016, the EMA’s Committee for Medicinal Products for Human Use (‘CHMP’) issued a positive opinion for the grant of an MA for Empliciti (Elotuzumab) in light of the data submitted and scientific discussion within that committee.

7 In parallel, the COMP reviewed whether the criteria for designation of Elotuzumab as an orphan medicinal product, as laid down in Article 3 of Regulation No 141/2000, were still met.

8 On 18 February 2016, the COMP issued an opinion in which it recommended that the orphan designation for Elotuzumab be withdrawn, finding that the prevalence criterion under Article 3(1)(a) of Regulation No 141/2000 was satisfied, but that the significant benefit criterion under Article 3(1)(b) of that regulation was not, in particular when compared with Kyprolis (Carfilzomib).

9 After the applicant had submitted detailed grounds of appeal on 4 March 2016 and provided oral explanations at the COMP meeting on 21-23 March 2016, the COMP issued its final opinion on 8 April 2016 and maintained its stance, recommending the removal of Elotuzumab from the Community Register of orphan medicinal products. According to the COMP, a comparison between Elotuzumab and Carfilzomib did not show that Empliciti (Elotuzumab) was of significant benefit to persons affected by multiple myeloma by comparison with the medicinal product Kyprolis (Carfilzomib), for which an MA had been granted on 19 November 2015, as published in the Official Journal of the European Union of 30 December 2015.

10 On 11 April 2016, the EMA informed the applicant that the negative opinion adopted by the COMP on 18 February 2016 and confirmed on appeal on 8 April 2016 was considered final and would be forwarded to the Commission. The applicant has acknowledged that it received the opinion on the same date via the electronic platform Eudralink.

11 On the basis of the opinions of the EMA, as formulated on 28 January 2016 by the CHMP and on 8 April 2016 by the COMP, the Commission adopted the implementing decision of 11 May 2016 granting marketing authorisation for the medicinal product for human use ‘Empliciti — elotuzumab’, pursuant to Regulation No 726/2004 (‘the Commission’s implementing decision of 11 May 2016’).

12 On 20 May 2016, for the first time, the Community Register of orphan medicinal products no longer included Elotuzumab, as the product had been removed from the register. On the same day, Elotuzumab was listed on the Community Register of non-active orphan medicinal products.

13 By email of 25 May 2016, an employee of the applicant’s asked a member of staff in the Commission’s Directorate-General (DG) for Health and Food Safety to provide her with a copy of the decision withdrawing the orphan designation of Elotuzumab and/or removing it from the Community Register of orphan medicinal products. Another member of staff from the same Directorate-General replied to her, stating that no Commission decision had been issued for such a withdrawal but that an opinion had been adopted by the EMA, and invited the applicant to contact the EMA Orphan Medicines Sector. There was no further communication on this point between the applicant and the Commission.

14 By application lodged at the Court Registry on 21 June 2016, the applicant brought the present action for annulment under Article 263 TFEU, directed against the European Commission or the EMA.

15 By document lodged at the Court Registry on 22 September 2016, the Commission lodged its defence.

16 By separate document lodged at the Court Registry on 28 September 2016, the EMA raised a plea of inadmissibility pursuant to Article 130(1) of the Rules of Procedure of the General Court.

17 The reply was lodged at the Court Registry on 30 November 2016. Also on that date, the applicant lodged its observations on the plea of inadmissibility.

18 On 20 February 2017, the Commission lodged its rejoinder at the Court Registry.

19 By order of the General Court of 4 April 2017, the plea of inadmissibility raised by the EMA was reserved until the Court ruled on the substance of the case.

23 On 22 January 2018, by way of measures of organisation of procedure under Article 89 of the Rules of Procedure, the Court requested the parties to reply to a series of questions. The parties complied with that request within the time allowed.

– annul an act of the Commission removing Elotuzumab from the Community Register of orphan medicinal products for human use and/or a possible act of the Commission or the EMA which found that Elotuzumab no longer met the criteria for designation as an orphan medicinal product when an MA was granted for Empliciti (Elotuzumab), pursuant to Regulation No 141/2000;

– in the alternative, reject the first part of the second plea as inadmissible and the rest of the action as unfounded;

27 Both the Commission and the EMA, the former in its defence and the latter in its plea of inadmissibility submitted by separate document, contend that the action is inadmissible.

28 The Commission and the EMA submit that the applicant’s claims in its application do not identify the contested act in a way that is sufficiently clear and precise, as required by settled EU case-law. They also state that the orphan designation of Elotuzumab was withdrawn pursuant to the Commission’s implementing decision of 11 May 2016, which at the same time granted an MA for the ‘non-orphan’ medicinal product Empliciti (Elotuzumab). In particular, they maintain that the decision to withdraw the designation was implicitly included in the Commission’s implementing decision of 11 May 2016, it being possible to infer the withdrawal from the express reference in the wording of that decision to the final COMP opinion of 8 April 2016. It is therefore that Commission implementing decision which should have been challenged.

29 The EMA, supported by the Commission, states that it did not issue any measure ordering the withdrawal of the orphan designation from Elotuzumab, since the power to adopt a decision of that type lies exclusively with the Commission, pursuant to Article 5(8) of Regulation No 141/2000 and the 2003 Communication from the Commission. Since the EMA is not the author of any such decision, the action directed against it must be declared inadmissible.

30 In addition, the Commission and the EMA maintain that the removal of Elotuzumab from the Community Register of orphan medicinal products is a purely administrative measure which does not produce binding legal effects, so that it cannot be the subject of an action for annulment. Therefore, the action should be declared inadmissible in so far as it relates to the removal. In that regard, the EMA states that the action directed against it is, in any event, inadmissible, since the EMA does not have the power to remove such a product from the register.

31 The applicant replies that its medicinal product would normally have to be withdrawn by means of a Commission decision but that it recognises that, due to the particular circumstances of the present case, there is uncertainty as to the identification of the measure contested. The applicant does not consider that the Commission’s implementing decision of 11 May 2016 constitutes such an act. Nevertheless, it states that ‘if the Court considers that the contested act is the decision of 11 May 2016 (and thus the severable part that holds withdrawal of the orphan designation), the [a]pplicant cannot be blamed for not having identified that decision as the contested act.’ In its reply to the measures of organisation of procedure ordered by the Court in order to clarify the meaning of those comments, the applicant essentially acknowledged that its request for annulment, as set out in the form of order sought in its application, in fact concerns the Commission’s implementing decision of 11 May 2016, in so far as that decision implicitly incorporates the decision to withdraw the designation of Elotuzumab as an orphan medicinal product. In that reply, the applicant also accepts that, from that perspective, its action cannot be directed against the EMA.

32 In that regard, it must be borne in mind that, pursuant to the first paragraph of Article 21 of the Statute of the Court of Justice of the European Union, applicable to proceedings before the General Court by virtue of Article 53 of the statute, and to Article 76(d) of the Rules of Procedure of the General Court, an application must, inter alia, contain the subject matter of the dispute and a brief statement of the pleas in law on which the application is based. The application is thus the formal document initiating proceedings, in which the applicant is required to state the subject matter of the dispute (see, to that effect, judgments of 25 September 1979, Commission v France, 232/78, EU:C:1979:215, paragraph 3, and of 20 May 2009, VIP Car Solutions v Parliament, T‑89/07, EU:T:2009:163, paragraph 110).

33 It is established case-law that the subject matter of the dispute as delimited in the application lodged pursuant to Article 263 TFEU must enable the General Court to identify precisely the measures which the applicant seeks to have set aside, it being understood that the Court cannot, in any event, rule ultra petita by granting a form of annulment which goes beyond that sought by the applicant (see, to that effect, judgments of 15 June 2006, Commission v France, C‑255/04, EU:C:2006:401, paragraph 24 and the case-law cited, and of 21 October 2015, Petco Animal Supplies Stores v OHIM — Gutiérrez Ariza (PETCO), T‑664/13, EU:T:2015:791, paragraph 24). Accordingly, such an application which does not expressly refer to the specific measure or measures annulment of which is sought and does not enable that measure or those measures to be identified with sufficient precision does not meet the requirements laid down by Article 76(d) of the Rules of Procedure (see judgment of 5 October 2009, de Brito Sequeira Carvalho and Commission v Commission and de Brito Sequeira Carvalho, T‑40/07 P and T‑62/07 P, EU:T:2009:382, paragraph 184 and the case-law cited; order of 27 November 2013, MAF v EIOPA, T‑23/12, not published, EU:T:2013:632, paragraph 29).

34 Nonetheless, the contested measure can be identified by implication from the statements and from the argument as a whole set out in the application (see order of 13 April 2011, Planet v Commission, T‑320/09, EU:T:2011:172, paragraph 23 and the case-law cited; judgment of 13 October 2015, Commission v Verile and Gjergji, T‑104/14 P, EU:T:2015:776, paragraph 108).

35 In the present case, the applicant formulates its request for annulment in the form of order sought in the application by referring in general terms to ‘an act of the … Commission removing [E]lotuzumab from the Community Register of orphan medicinal products for human use and/or a possible act of the … Commission or the [EMA] determining that the orphan designation criteria for [E]lotuzumab were not met any more’, without indicating expressly the specific act or acts which it seeks to have annulled. Nevertheless, although the applicant recognises in the application that it is not able to identify specifically the measure contested due to the particular circumstances of the present case, the subject matter of its application for annulment is itself identified precisely. The applicant contests the act which was responsible for the actual removal of its medicinal product from the Community Register of orphan medicinal products and maintains that that situation is necessarily based on an express or implied decision.

36 It should also be noted that it is clear from the pleadings lodged by the Commission and the EMA that the defendants have not failed to understand that it is the applicant’s intention to seek the annulment of the act that was responsible for the actual removal of Elotuzumab from the Community Register of orphan medicinal products. However, the parties disagree as to the actual identity of that act. On the one hand, the defendants maintain that what is being contested is an automatic effect of the Commission’s implementing decision of 11 May 2016 and that it is therefore that decision that should have been challenged as there is no other decision. On the other hand, as is apparent from paragraph 31 above, the applicant has expressed its doubts as to whether the decision contested was the Commission’s implementing decision of 11 May 2016 granting it an MA.

37 It should also be acknowledged that the circumstances of the present case are particular. As is apparent from the documents before the Court, the Commission first of all adopted a decision, on 9 August 2012, designating Elotuzumab as an orphan medicinal product for the treatment of multiple myeloma and, in pursuance of that decision, Elotuzumab was included in the Community Register of orphan medicinal products. Next, in the MA procedure for Empliciti (Elotuzumab), the Commission adopted the Commission’s implementing decision of 11 May 2016 granting an MA for Empliciti (Elotuzumab). Subsequently, on 20 May 2016, for the first time, that register no longer included Elotuzumab, as it had been removed from the register. Moreover, in response to a request from the applicant on 25 May 2016, a member of the Commission’s staff indicated that the latter had not made any decision concerning the withdrawal of the orphan designation of Elotuzumab. Lastly, in their pleadings, the Commission and the EMA confirm that no other decision apart from that of 11 May 2016 exists. In those particular circumstances, the applicant cannot be criticised for not being able to identify specifically the act that was responsible for the actual removal of Elotuzumab from the Community Register of orphan medicinal products.

38 It should be noted in that regard that Article 5(12)(b) of Regulation No 141/2000 provides that a designated orphan medicinal product is to be removed from the Community Register of orphan medicinal products if it is established that the criteria laid down in that regulation are no longer met in respect of the medicinal product concerned. It follows that removal is the direct result of the decision establishing that the criteria for orphan designation are no longer met. Removal, per se, is a purely administrative measure that produces no binding legal effect and it cannot therefore be regarded as a measure against which an action for annulment may be brought under Article 263 TFEU. Accordingly, the action must be declared inadmissible in so far as it concerns such removal.

39 In the present case, the actual removal of Elotuzumab from the Community Register of orphan medicinal products necessarily presupposes the existence of a decision establishing that that medicinal product no longer met the criteria for orphan designation, in accordance with Article 5(12)(b) of Regulation No 141/2000. Without there being any need at this stage to determine, as part of the examination of whether the action is admissible, what form such a decision should take, which is the subject matter of the second plea in law, it cannot be ruled out that that decision was an implied decision. Nor can it be ruled out that that decision was included by implication in the Commission’s implementing decision of 11 May 2016, as that is the only express decision which refers to the COMP opinion of 8 April 2016 and grants an MA for Empliciti (Elotuzumab) without stating that it is an orphan medicinal product.

40 Admittedly, the applicant states that the decision contested is not the Commission’s implementing decision of 11 May 2016, as argued by the Commission and the EMA. Nevertheless, it recognises that the decision establishing that the criteria for the designation of Elotuzumab as an orphan medicinal product were no longer met could be an implied decision. When questioned on that point by the Court by way of measure of organisation of procedure, the applicant gave a reply from which it is apparent that it accepted, in essence, that its request for annulment, as formulated in the form of order sought in its application, is in fact directed at the Commission’s implementing decision of 11 May 2016, as that decision included, by implication, the decision to withdraw the designation of Elotuzumab as an orphan medicinal product. In that reply, the applicant also accepted, correctly, that, from that perspective, its action cannot be directed at the EMA because the EMA is not responsible for that implementing decision (see, to that effect, judgment of 8 October 2008, Sogelma v AER, T‑411/06, EU:T:2008:419, paragraph 49; see also, to that effect, judgment of 21 October 2010, Agapiou Joséphidès v Commission and EACEA, T‑439/08, not published, EU:T:2010:442, paragraph 34 and the case-law cited).

41 Accordingly, in the light of the case-law cited in paragraphs 32 to 34 above and bearing in mind the particular circumstances of the present case, the Court finds that the claims for annulment in the action in fact seek the annulment of the Commission’s implementing decision of 11 May 2016, only in so far as that decision includes, by implication, the decision withdrawing the designation of Elotuzumab as an orphan medicinal product (‘the decision at issue’). The Commission’s express decision of 11 May 2016 granting an MA to Empliciti (Elotuzumab) does not form the subject matter of those claims for annulment.

42 Moreover, it is established case-law that the form in which an act or a decision is adopted is, as a general rule, irrelevant for the purpose of determining whether an action for annulment is admissible. It is therefore, in principle, irrelevant for the classification of the act in question whether or not it satisfies certain formal requirements, that is to say, whether it is duly named by its author, whether sufficient reasons are given, and whether it mentions the provisions providing the legal basis for it. If it were otherwise, the Commission could avoid review by the EU Courts simply by failing to comply with such formal requirements. According to settled case-law, as the European Union is a community based on the rule of law in which its institutions are subject to judicial review of the compatibility of their acts with the Treaty, the procedural rules governing actions brought before the EU courts must be interpreted in such a way as to ensure, wherever possible, that those rules are implemented in such a way as to contribute to the attainment of the objective of ensuring effective judicial protection of an individual’s rights under EU law (see judgment of 17 July 2008, Athinaïki Techniki v Commission, C‑521/06 P, EU:C:2008:422, paragraphs 43 to 45 and the case-law cited).

43 Therefore, the action as thus delimited and as directed against the Commission must be declared admissible and the substance of the claims examined.

44 Furthermore, it should be noted that, as is apparent from the considerations set out in particular in paragraph 38 above, the action must be declared inadmissible in so far as it relates to the removal of Elotuzumab from the Community Register of orphan medicinal products. Similarly, as is apparent from the considerations set out in particular in paragraph 40 above, the action must be declared inadmissible in so far as it is directed against the EMA.

45 In support of its action, the applicant relies on three pleas in law. The first plea alleges infringement of Article 5(12)(b) of Regulation No 141/2000, in conjunction with the principle of proportionality The second plea alleges infringement of that provision, read in conjunction with Article 5(8) of that regulation. The third plea, which was raised at the stage of the reply, alleges failure to identify the legal basis and failure to state reasons.

46 The Court considers it appropriate to begin by examining the third plea, followed by the first and second pleas.

Third plea, alleging failure to identify the legal basis and lack of reasoning

47 By its third plea, raised at the stage of the reply, the applicant submits that the decision at issue does not identify the legal basis, which constitutes an infringement of the duty to state reasons and invalidates the decision. According to the case-law of the Court of Justice, the obligation to identify the legal basis of an act is part of the duty to state reasons and is of constitutional significance. In addition, the duty to state reasons is a matter of public policy that must be raised by the EU judicature of its own motion and may be examined at any stage in the proceedings.

48 In particular, the applicant submits that the decision at issue fails to mention Regulation No 141/2000 and refers only to Regulation No 726/2004 as a legal basis. However, only Regulation No 141/2000 may constitute the legal basis of a decision withdrawing the designation of a medicinal product as an orphan medicinal product. In addition, the applicant notes that the only reference to the orphan medicinal products regime is the reference to the COMP opinion of 8 April 2016 in the citations of the decision at issue. That opinion refers to Article 5(12)(b) of Regulation No 141/2000, but only as the legal basis for the COMP review. No further reference is made to a legal basis for any subsequent Commission decision. In any event, an indirect reference in a Commission decision to a legal basis, mentioned in a preparatory opinion that is referred to in that decision, will not meet the standards for compliance with a principle that is of constitutional significance.

49 The Commission contends that the third plea should be rejected as inadmissible or, in any event, as unfounded.

50 It should be noted first of all in that regard that it is clear from the Court of Justice’s case-law that the obligation to identify the legal basis of a measure is related to the duty to state reasons (see judgment of 1 October 2009 Commission v Council, C‑370/07, EU:C:2009:590, paragraph 38 and the case-law cited).

51 Next, it should be recalled that, according to settled case-law, compliance with the duty to state reasons is a matter of public policy which may be raised by the parties at any stage of the proceedings or indeed by the court of its own motion (see, to that effect, judgments of 20 February 1997, Commission v Daffix, C‑166/95 P, EU:C:1997:73, paragraph 25; of 8 October 2008, Carbone-Lorraine v Commission, T‑73/04, EU:T:2008:416, paragraph 127; and of 8 October 2015, Rosian Express v OHIM (shape of a games box), T‑547/13, EU:T:2015:769, paragraph 13). The third plea must therefore be declared admissible.

52 It must also be borne in mind that, according to consistent case-law, the extent of the obligation to state reasons laid down in Article 296 TFEU depends on the nature of the measure in question and on the context in which it was adopted. The statement of reasons must disclose in a clear and unequivocal fashion the reasoning followed by the institution which adopted the measure in such a way as to enable the persons concerned to ascertain the reasons for the measure, so that they can defend their rights and ascertain whether or not the decision is well founded and the European Union judicature to review the lawfulness of the measure. It is not necessary for the reasoning to go into all the relevant facts and points of law, since the question whether the statement of reasons meets the requirements of Article 296 TFEU must be assessed with regard not only to its wording but also to its context and to all the legal rules governing the matter in question (judgments of 2 April 1998, Commission v Sytraval and Brink’s France, C‑367/95 P, EU:C:1998:154, paragraph 63, and of 30 November 2011, Sniace v Commission, T‑238/09, not published, EU:T:2011:705, paragraph 37).

53 Moreover, 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 11 June 2015, Laboratoires CTRS v Commission, T‑452/14, not published, EU:T:2015:373, paragraph 57 and the case-law cited).

54 Similarly, it follows from case-law that where a decision 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 judgment of 11 June 2015, Laboratoires CTRS v Commission, T‑452/14, not published, EU:T:2015:373, paragraph 60 and the case-law cited).

55 In the present case, it should be noted that while it is true that the decision at issue does not expressly mention Regulation No 141/2000, which forms the legal basis of the withdrawal of the designation in question as an orphan medicinal product, that decision nonetheless refers to the COMP opinion of 8 April 2016 in its preamble. According to case-law, it is not necessary for an express reference to be given in a measure to the legal basis for the measure if that basis may be determined from other parts of the measure (see, to that effect, judgment of 1 October 2009, Commission v Council, C‑370/07, EU:C:2009:590, paragraph 56).

56 Moreover, the COMP opinion of 8 April 2016, which recommended the removal of Elotuzumab from the Community Register of orphan medicinal products, must, according to the case-law cited in paragraph 54 above, be regarded as an integral part of the statement of reasons for the decision at issue, since that decision simply confirms that opinion. In addition, the opinion refers several times to Regulation No 141/2000 and specifies the legal basis applicable to the withdrawal of the designation of a product as an orphan medicinal product.

57 It follows that the COMP opinion of 8 April 2016, which is mentioned in the preamble to the decision at issue and forms an integral part of that decision, is part of that decision, within the meaning of the case-law cited in paragraph 55 above, in reliance on which the legal basis of the withdrawal of the orphan designation of Elotuzumab may be determined. Moreover, it should be noted that the applicant is well aware of the context, as it accepts that it received that opinion in good time and that it was also aware of the legal framework under which the opinion was issued, especially as it was actively involved in the procedure for the re-evaluation of the designation criteria in question. Therefore, the applicant cannot reasonably claim that it was uncertain as to the legal basis for and the reasons which led to the adoption of the decision at issue.

58 As a consequence, it must be concluded that the decision at issue complies with Article 296 TFEU in so far as it refers, in its preamble, to the COMP opinion of 8 April 2016, which itself forms an integral of the statement of reasons for that decision, gives the reasons why the designation of Elotuzumab as an orphan medicinal product had to be withdrawn and expressly refers to Regulation No 141/2000. Accordingly, the third plea in law must be rejected as unfounded.

The first plea, alleging infringement of Article 5(12)(b) of Regulation No 141/2000, in conjunction with the principle of proportionality

59 By its first plea, the applicant alleges infringement of Article 5(12)(b) of Regulation No 141/2000, in conjunction with the principle of proportionality. This plea is divided in three parts:

– The first part of the first plea, concerning the fact that the recently authorised medicinal product Kyprolis (Carfilzomib) was taken into account

60 By the first part of its first plea, the applicant claims that the decision at issue infringed Article 5(12)(b) of Regulation No 141/2000 and the principle of proportionality, by taking into account, incorrectly, another medicinal product, namely Kyprolis (Carfilzomib), in the review of the significant benefit criterion under Article 3(1)(b) of that regulation.

61 In that regard, the applicant maintains that Empliciti (Elotuzumab) should not have been compared with Kyprolis (Carfilzomib), as the latter was granted an MA on 19 November 2015, that is to say, after the development programme for Empliciti (Elotuzumab) had been completed by the applicant with a view to applying for an MA for that medicinal product. In any event, the applicant considers that Empliciti (Elotuzumab) should not have been compared with the authorised medicinal product Kyprolis (Carfilzomib) after 3 July 2015, the date on which it submitted its application for an MA for Empliciti (Elotuzumab). Accordingly, recently authorised medicinal products should not be taken into account when conducting a review under Article 5(12)(b) of Regulation No 141/2000. Any other interpretation would jeopardise compliance with the principle of proportionality and the attainment of the objective of the regulation, which is to encourage pharmaceutical laboratories to invest in research and development of new products by granting them market exclusivity.

62 Furthermore, the applicant considers that taking Kyprolis (Carfilzomib) into account is unfair because there is not enough time to submit sufficient data, in particular where a direct comparison is to be made.

63 The Commission disputes the applicant’s arguments and contends that the first part of the first plea should be rejected as unfounded.

64 In that regard, it should be noted that Article 3(1)(b) of Regulation No 141/2000 provides that ‘[a] medicinal product shall be designated as an orphan medicinal product if its sponsor can establish … that there exists no satisfactory method of diagnosis, prevention or treatment of [a life-threatening or chronically debilitating] condition [affecting not more than five in ten thousand persons in the European Union] that has been authorised in the [European Union], or, if such method exists, that the medicinal product will be of significant benefit to those affected by that condition’. The term ‘significant benefit’ is defined in Article 3(2) of Commission Regulation (EC) No 847/2000 of 27 April 2000 laying down the provisions for implementation of the criteria for designation of a medicinal products as an orphan medicinal products and definitions of the concepts ‘similar medicinal product’ and ‘clinical superiority’ (OJ 2000 L 103, p. 5) as ‘a clinically relevant advantage or a major contribution to patient care’.

65 It is clear from Article 3(1)(b) of Regulation No 141/2000 and the definition of ‘significant benefit’ in Regulation No 847/2000 that such a benefit must be established only in the specific case where a satisfactory method of diagnosis, prevention or treatment of the condition in question has already been authorised (judgment of 9 September 2010, Now Pharm v Commission, T‑74/08, EU:T:2010:376, paragraph 41).

66 The abovementioned provisions have previously led the Court to describe a significant benefit as constituting a conclusion that must be drawn from a comparison of the medicinal product that is being evaluated with medicinal products that have already been authorised. In particular, the Court has held that significant benefit is established by carrying out a comparison with an existing authorised medicinal product or method. Indeed, the ‘clinically relevant advantage’ and the ‘major contribution to patient care’, which enable the potential orphan medicinal product to be described as being of significant benefit, can be established only by comparison with treatments that have already been authorised. That interpretation is confirmed by the 2003 Communication from the Commission, which states that ‘[t]he applicant is required to establish significant benefit compared with an existing authorised medicinal product or method at the time of designation’ (judgment of 9 September 2010, Now Pharm v Commission, T‑74/08, EU:T:2010:376, paragraphs 43 and 44).

67 It follows that the wording of Article 3(1)(b) of Regulation No 141/2000 and, in particular the phrase ‘that has been authorised in the [European Union]’, as well as the interpretation of this provision given by the Court justify the conclusion that all authorised medicinal products must be taken into account for the purpose of establishing significant benefit. The relevant regulation in the present case does not provide for any exception in that respect.

68 As observed by the Commission and the EMA, there is nothing to support the claim that medicinal products which were authorised after the development of the orphan medicinal product concerned or, at the very least, those which were authorised after the MA application was submitted for the latter product should not be taken into account. If the legislature had intended to exclude medicinal products authorised after the MA application had been submitted for the medicinal product concerned and before the end of the review of the designation criteria laid down in Article 3(1)(b) of Regulation No 141/2000, it could have done so.

69 Moreover, it should be noted that the notion of the ‘[completion] of the development programme’ for the orphan medicinal product referred to by the applicant does not appear, as such, in Regulation No 141/2000 and can therefore be of no legal significance in connection with that regulation. That term is also vague and does not make it possible to determine the precise date of that ‘completion’.

70 Similarly, with regard to the argument put forward by the applicant in the alternative that Empliciti (Elotuzumab) should not have been compared with the authorised medicinal product Kyprolis (Carfilzomib) after 3 July 2015, that is, after the date on which the MA application was submitted for the medicinal product concerned, it should be observed that neither Article 5(12) of Regulation No 141/2000 nor Article 7(3) of that regulation refer to such an application but rather to the grant of an MA for the medicinal product concerned, which necessarily takes place at a later stage. That explains why the 2003 Communication from the Commission states that ‘the most appropriate time to reconsider designation is when the [MA] of a designated orphan medicinal product is imminent, that is at around the time of an expected positive opinion from the [CHMP]’. In that regard, it should also be noted that, in accordance with Article 8(1) of Regulation No 141/2000, market exclusivity for an orphan medicinal product follows as a result of the grant of an MA for that medicinal product. The conditions of the MA are therefore decisive for the purpose of determining whether or not Article 8(1) of that regulation is applicable, with the result that the date on which the MA was granted is the deadline for establishing whether the designation criteria are still met.

71 Moreover, if it were accepted that, as the applicant claims, medicinal products which obtained an MA after the application was submitted for an MA in respect of the medicinal product concerned should not be compared with the latter, that could result in infringement of Article 7(3) of Regulation No 141/2000, as that provision prohibits the grant of an MA for therapeutic indications which do not meet the designation criteria set out in Article 3 of the regulation. Indeed, under Article 7(3) of Regulation No 141/2000 those criteria must still be met when an MA is granted for an orphan medicinal product. Similarly, it is clear from a reading of that provision in conjunction with Article 5(12) of that regulation that the designation criteria must be reviewed before an MA is granted for the medicinal product concerned, so that the relevant time for establishing whether those criteria are still met, by, inter alia, comparing medicinal products in order to ascertain the significant benefit of the medicinal product concerned, is the time at which an MA is granted for that product.

72 It follows that, in the present case, the COMP was under a legal obligation to evaluate the potential significant benefit of Empliciti (Elotuzumab) as compared with the authorised medicinal product Kyprolis (Carfilzomib). If the COMP had not assessed significant benefit by comparing Empliciti (Elotuzumab) with Kyprolis (Carfilzomib), it would not have been possible to establish, in accordance with Article 5(12) of Regulation No 141/2000, whether the designation criteria set out in Article 3 of the regulation were still met in so far as concerns Empliciti (Elotuzumab).

73 Moreover, it should be noted that it was the applicant itself which referred to Kyprolis (Carfilzomib) in its updated report of December 2015, which was submitted in the designation review procedure provided for in Article 5(12) of Regulation No 141/2000. The applicant therefore referred to that recently authorised medicinal product in connection with the review of the designation criteria set out in Article 3 of the regulation. Accordingly, it cannot criticise the COMP for taking Kyprolis (Carfilzomib) into account in order to establish whether Empliciti (Elotuzumab) still met the significant benefit criterion.

74 Furthermore, it should be noted that, as is apparent from the foregoing, there was no breach of the principle of proportionality. In that regard, the assessments concerning the significant benefit criterion, in the designation review procedure under Article 5(12) of Regulation No 141/2000, were carried out objectively, from a purely scientific point of view, so that the COMP had no scope for discretion as regards recommending to the Commission that it remove the medicinal product in question from the Community Register of orphan medicinal products.

75 It follows from all the foregoing considerations that the first part of the first plea in law, relating to the fact that account was taken of the recently authorised medicinal product Kyprolis (Carfilzomib), cannot succeed. That part of the plea must therefore be rejected.

– The second part of the first plea, concerning the alleged failure to provide conclusive evidence establishing the lack of significant benefit

76 By the second part of its first plea, the applicant submits that the decision at issue infringed Article 5(12)(b) of Regulation No 141/2000 and the principle of proportionality, by relying, incorrectly, on data that did not clearly demonstrate that Empliciti (Elotuzumab) did not provide significant benefit as compared with Kyprolis (Carfilzomib).

77 In that regard, the applicant submits that Article 5(12)(b) of Regulation No 141/2000 clearly states that a designated orphan medicinal product may be removed from the Community Register of orphan medicinal products only ‘if it is established … that the criteria laid down in Article 3 [of that regulation] are no longer met’. The wording ‘it is established’ clearly implies that the data available at the time of review must allow a firm conclusion that the designation criteria are no longer met. That means that, in order to withdraw the orphan designation from Empliciti (Elotuzumab), there would have had to be solid and conclusive evidence that the medicinal product has no significant benefit, which was not the case.

78 The applicant claims that the re-evaluation of the designation criteria under the procedure referred to in Article 5(12)(b) of Regulation No 141/2000 differs from the examination of those criteria at the time of the application for initial designation. In the case of the significant benefit criterion assessed as part of the application for initial designation, it is for the sponsor to establish that its medicinal product offers significant benefit compared with other authorised medicinal products, pursuant to Article 3 of that regulation. On the other hand, for the re-evaluation under Article 5(12)(b) of the regulation, compelling evidence is needed that the designated medicinal product is no longer of significant benefit compared with other authorised medicinal products. According to the applicant, in the case of Empliciti (Elotuzumab), the COMP took the opposite approach. It is obvious from the language used in the COMP’s opinion of 8 April 2016 that it expected to receive conclusive evidence of significant benefit and that it considered that the available data comparing Empliciti (Elotuzumab) and Kyprolis (Carfilzomib) were inconclusive. The COMP erred as regards the standard of proof.

79 In addition, the applicant maintains that, by applying an incorrect criterion, the EMA also implemented the procedure under Article 5(12) of Regulation No 141/2000 in a manner that went beyond what was appropriate and necessary to achieve the objective of that regulation.

80 The Commission disputes the applicant’s arguments and contends that the second part of the first plea should be rejected as unfounded.

81 In that regard, it should be recalled that Article 5(12)(b) of Regulation No 141/2000 provides that a designated orphan medicinal product is to be removed from the Community Register of orphan medicinal products ‘if it is established before the [MA] is granted that the criteria laid down in Article 3 [of the regulation] are no longer met in respect of the medicinal product concerned’. It follows from that provision that the criteria for orphan designation are to be reviewed before an MA is granted. Thus, where a sponsor submits an MA application in respect of a designated orphan medicinal product, he triggers at the same time a procedure for re-evaluating those designation criteria.

82 The responsibility for assessing whether such an application meets the designation criteria lies solely with the COMP, which must issue a scientific opinion on the initial designation. An MA will confer entitlement to market exclusivity, within the meaning of Article 8 of Regulation No 141/2000, only if the COMP has confirmed, at the conclusion of its scientific assessment, that the objective designation criteria set out in Article 3(1) of the regulation are met. According to Article 7(3) of the regulation, the MA granted for an orphan medicinal product covers only those therapeutic indications which fulfil the criteria set out in Article 3.

83 It is apparent from a reading of Article 5(12)(b) of Regulation No 141/2000 in conjunction with Article 7(3) of the regulation that at the time of the MA the COMP is to carry out a complete re-evaluation of the designation criteria in a factual situation that is different from that which led to the initial designation. In order to determine whether the medicinal product in question meets those criteria at the time of the MA, that new assessment must take account of evidence that has come to light since the grant of the initial designation, including new medicinal products which have been authorised in the meantime. Thus, if it is shown that the basis on which the initial designation was granted has changed, in particular where that designation was based on a significant benefit which no longer exists due to the existence of new authorised medicinal products at the time of the MA, the medicinal product concerned must be removed from the Community Register of orphan medicinal products, as stated in the 2003 Communication from the Commission.

84 It follows that, as regards the significant benefit criterion referred to in Article 3(1) of Regulation No 141/2000, there must be a positive finding that that criterion is met once again at the time of the MA. In order to confirm in its opinion that the orphan designation attributed to the medicinal product concerned should be maintained, the COMP must satisfy itself, scientifically and objectively, that the significant benefit criterion is met. Accordingly, in the absence of conclusive evidence proving significant benefit at the time of the MA, the COMP is required to conclude that the designation criteria laid down in Article 3 of the regulation are no longer met and, therefore, recommend that the Commission remove the medicinal product concerned from the Community Register of orphan medicinal products. Thus, in order to avoid such removal, the sponsor must provide sufficient data to establish significant benefit, in the light of the new circumstances prevailing at the time the MA is granted.

85 In the present case, it is clear from the COMP opinion of 8 April 2016 that the applicant did not produce sufficient data to enable it to be established that Empliciti (Elotuzumab) was still of significant benefit to those affected by the condition in question. It also follows from that opinion that the available data comparing Empliciti (Elotuzumab) with Kyprolis (Carfilzomib) were conclusive as to the fact that the former medicinal product was not of significant benefit by comparison with the latter product. The COMP therefore relied on data which enabled it to reach the clear conclusion that the significant benefit criterion was no longer met in so far as concerns Empliciti (Elotuzumab) in the review provided for in Article 5(12)(b) of Regulation No 141/2000.

86 Therefore, the applicant has no valid grounds for criticising the COMP for not basing its decision on conclusive evidence establishing that Empliciti (Elotuzumab) was not of significant benefit. In any event, the COMP was obliged to conclude that the designation criteria laid down in Article 3 of Regulation No 141/2000 were not met, as no conclusive data establishing significant benefit had been produced at the time of the MA. As a consequence, contrary to what is claimed by the applicant, the COMP did not make an error as regards the standard of proof required under Article 5(12)(b) of Regulation No 141/2000, with the result that no infringement of that provision may be attributed to it.

87 Furthermore, it should be noted, as is apparent from the foregoing and for the same reasons as those given in paragraph 74 above, that the principle of proportionality was not infringed.

88 It follows from all the foregoing considerations that the second part of the first plea in law, concerning the alleged lack of conclusive evidence establishing that there was no significant benefit, cannot succeed. That part must therefore be rejected.

– The third part, alleging the application of an overly rigid test for the assessment of significant benefit

89 By the third part of its first plea, which was raised as an alternative to the second part of the plea, the applicant submits that the decision at issue infringed Article 5(12)(b) of Regulation No 141/2000 and the principle of proportionality by applying, incorrectly, an overly rigid test to assess the significant benefit concerned.

90 In that regard, the applicant claims that, even though the COMP had to verify whether the available data supported the conclusion that Empliciti (Elotuzumab) offered significant benefit compared with Kyprolis (Carfilzomib), the COMP should not have fixed an overly rigid test for evidence of significant benefit, but instead should have: (i) conducted a more global assessment, focusing on all of the evidence that could substantiate its claim of significant benefit; (ii) used the general criterion of benefit for the patient; and (iii) applied a standard of proof that did not require conclusive proof and could allow for estimates and assumptions based on the available data, especially when taking into account the relevant circumstances, including the practical impossibility for the applicant of producing new comparative data.

91 In the first place, the applicant submits that the COMP’s opinion of 8 April 2016 shows that the COMP erroneously applied a formalistic and fragmented comparative method in reviewing the significant benefit at issue. The COMP reviewed, one after the other, various points raised by the applicant as evidence of significant benefit and rejected them because none of them was, in the COMP’s view, sufficient on its own to establish significant benefit. The COMP therefore failed to make a more global assessment of the efficacy and safety profile of Empliciti (Elotuzumab).

92 In the second place, the applicant maintains that the assessment of the significant benefit at issue should have been based on the yardstick of benefit for the patient, as follows from the wording of Article 3(1)(b) of Regulation No 141/2000, which refers to ‘significant benefit to those affected by [the] condition’. According to the applicant, the COMP should have taken account of the fact that, when a medicinal product can be of therapeutic importance to certain patients, because of their specific characteristics, the product brings benefit, because some patients may react better to certain treatments than others. The importance of the availability of new treatment options is particularly well recognised in relation to the condition in question.

93 In the third place, the applicant submits that the COMP should have accepted the possibility of finding significant benefit on the basis of best estimates or even assumptions rather than insisting on conclusive evidence. In that regard, the applicant states that the use of assumptions is common at the initial designation phase, as provided for in the 2003 Communication from the Commission. Moreover, there is nothing in Regulation No 141/2000 that prevents the use of assumptions, including for the review of designation under Article 5(12)(b) of that regulation, which is in line with recital 4 of Regulation No 847/2000, which states that ‘it is not appropriate to lay down overly prescriptive requirements to establish that the criteria [for designating a medicinal product as an orphan medicinal product] are met’. In addition, it would have been appropriate, in the present case, to use such assumptions because it was de facto impossible for the applicant to provide conclusive evidence of significant benefit of its medicinal product as compared with Kyprolis (Carfilzomib) in the form of a direct comparative study.

94 The Commission disputes the applicant’s arguments and contends that the third part of the first plea should be rejected as unfounded.

95 It should be noted in that regard, first of all, that the procedure for the designation of orphan medicinal products is an administrative procedure involving complex scientific assessments (judgment of 9 September 2010, Now Pharm v Commission, T‑74/08, EU:T:2010:376, paragraph 77). In that area of orphan medicinal products, in most cases the Commission endorses the opinions of the COMP unless it has other adequate sources of information in the field in question (judgment of 9 September 2010, Now Pharm v Commission, T‑74/08, EU:T:2010:376, paragraph 75).

96 Next, it should be noted that, according to case-law, where the Commission must undertake complex technical and/or scientific assessments, it enjoys broad discretion. As part of its judicial review, the EU judicature must determine whether the relevant procedural rules have been complied with, whether the facts established by the Commission are correct and whether there has been a manifest error of appraisal of those facts or a misuse of powers ((judgment of 9 September 2010, Now Pharm v Commission, T‑74/08, EU:T:2010:376, paragraph 111 and the case-law cited).

97 Moreover, the Court has held that a feature of the procedure introduced by Article 5 of Regulation No 141/2000 is the essential part assigned to an objective and in-depth scientific assessment by the COMP of the effect of the potential medicinal products considered. Since the Commission is not in a position to carry out scientific assessments of the efficacy and/or harmfulness of a medicinal product during the orphan medicinal product designation procedure, the aim of the mandatory consultation of the COMP is to provide the Commission with the evidence of scientific assessment, which is essential for it to be able to determine, in full knowledge of the facts, the appropriate measures to ensure a high level of public health protection. Thus, although the COMP’s opinion does not bind the Commission, it is nonetheless extremely important (judgment of 9 September 2010, Now Pharm v Commission, T‑74/08, EU:T:2010:376, paragraph 112 and the case-law cited).

98 It must be noted that, in this case, the Commission did not depart from the COMP’s opinion of 8 April 2016 and therefore endorsed the findings of that opinion. Accordingly, the judicial review which falls to the Court, in particular its review as to whether there has been a manifest error of assessment, must be carried in respect of all the considerations set out in that opinion, which forms an integral part of the decision at issue.

99 In that connection, it should be noted that the Court cannot substitute its own assessment for that of the COMP. It is only the proper functioning of the COMP, the internal consistency of the opinion and the statement of reasons contained therein which are subject to judicial review. As regards the last aspect, the Court is empowered only to examine whether the COMP opinion contains a statement of reasons from which it is possible to ascertain the considerations on which the opinion is based, and whether it establishes a comprehensible link between the medical and/or scientific findings and its conclusions (judgment of 26 November 2002, 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, EU:T:2002:283, paragraph 200).

100 In the present case, the COMP opinion of 8 April 2016 contains a statement of reasons from which it is possible to ascertain the considerations on which the opinion is based and to establish a comprehensible link between its conclusions and the medical and/or scientific findings. It cannot therefore be validly claimed that the statement of reasons in that opinion is vitiated by unlawfulness in that regard.

101 Furthermore, the Court has stated that it is apparent from the wording of Article 3(1)(b) of Regulation No 141/2000 and the spirit underlying the system established by that regulation that the criteria for a finding of significant benefit are strict (see judgment of 22 January 2015, Teva Pharma and Teva Pharmaceuticals Europe v EMA, T‑140/12, EU:T:2015:41, paragraph 65 and the case-law cited).

102 In the present case, the COMP’s assessment and its opinion of 8 April 2016 comply with the requirements laid down in the legislation governing orphan medicinal products and do not infringe Article 5(12)(b) of Regulation No 141/2000. Indeed, it is apparent from that opinion that the COMP applied the criteria for establishing whether there was a significant benefit strictly. Similarly, it should be noted that, as is clear from, inter alia, paragraph 100 above, there was no manifest error of assessment in that regard.

103 It follows that, in so far as the complaints put forward by the applicant in support of the third part of the first plea challenge the decision at issue on the ground that it applied an overly rigid test for establishing significant benefit, those complaints must be rejected as unfounded.

104 Moreover, it should be noted that, as is apparent from the foregoing and for the same reasons as those set out in paragraph 74 above, the principle of proportionality was not infringed.

105 It follows from all the foregoing considerations that the third part of the first plea in law, alleging the application of an overly rigid test for the assessment of significant benefit, cannot succeed. As a consequence, that part of the plea must be rejected, as must the first plea in its entirety, therefore, as unfounded.

The second plea, alleging infringement of Article 5(12)(b) of Regulation No 141/2000, read in conjunction with Article 5(8) of that regulation

106 By the first part of its second plea, the applicant submits that the decision at issue infringes Article 5(12)(b) of Regulation No 141/2000, read in conjunction with Article 5(8) of that regulation, since no formal Commission decision was taken to withdraw the designation of Elotuzumab as an orphan medicinal product. A formal decision was necessary because: (i) the initial designation was made by means of a decision; (ii) the EMA had no power to take a decision under Article 5(12) of Regulation No 141/2000; and (iii) the 2003 Communication from the Commission confirms that a Commission decision is necessary. In addition, the applicant is of the view that any implied decision to withdraw orphan designation is invalid, since withdrawal must be the result of a formal decision of the Commission. Thus, even assuming that the decision at issue exists, it was not adopted in the proper legal form.

107 By the second part of the second plea, the applicant claims that the decision at issue also infringed those provisions because it would appear to have been adopted after or at the same time as the Commission’s implementing decision of 11 May 2016 granting an MA for Empliciti (Elotuzumab). Article 5(12)(b) of Regulation No 141/2000 presupposes that a decision, whether express, implied or tacit, to withdraw orphan designation will be adopted before the MA decision. A withdrawal decision that is adopted alongside an MA would not be valid either, since Article 5(12)(b) requires a formal position to be adopted ‘before the [MA] is granted’. That position should not be confused with the COMP opinion, as Article 5(8) of the regulation makes it clear that the opinion is only advisory and the EMA has no decision-making power in relation to the procedures under Article 5(12)(b).

108 As regards the first part of the second plea, the Commission submits that it is inadmissible. It maintains that the absence of a formal decision is not challengeable in an action for annulment. In order to challenge such an omission, the applicant would have had to bring an action for failure to act.

109 In any event, the Commission is of the view that the first part of the second plea is unfounded.

110 As regards the second part of the second plea, the Commission contends that that part must also be rejected.

111 The Court considers it appropriate to examine both parts of the second plea together.

112 With regard, in the first place, to the admissibility of the first part of the second plea, the applicant does not claim that there was no decision to withdraw the orphan designation of Elotuzumab, but takes issue with the Commission for failing to adopt such a decision in an express form. The applicant’s criticism is not therefore based on the claim that no such withdrawal decision was taken but on the form that such a decision should take. Therefore, the plea of inadmissibility raised by the Commission and the EMA in that regard must be disregarded.

113 As regards, in the second place, the form of the withdrawal decision at the time of its adoption, it should be noted that Article 5(8) of Regulation No 141/2000 provides that the Commission is required to adopt a decision whether or not to designate the medicinal product concerned as an orphan medicinal product. That decision must be made within 30 days of receipt of the final COMP opinion.

114 Moreover, Article 5(12)(b) of Regulation No 141/2000, which concerns the re‑evaluation of the designation criteria relating to the MA, provides that a designated orphan medicinal product is to be removed from the Community Register of orphan medicinal products ‘if it is established before the [MA] is granted that the criteria [for orphan designation] laid down in Article 3 [of that regulation] are no longer met in respect of the medicinal product concerned’. According to the 2003 Communication from the Commission, before such a product may be so removed on that basis, those criteria must be reviewed by the COMP, which is responsible for giving a scientific opinion on the initial designation. Moreover, as the initial designation leads to the inclusion of a medicinal product in that register, removal from the register must follow the same procedure of scientific opinion followed by a legal decision by the Commission in accordance with Article 5(8) of Regulation No 141/200.

115 It follows that where the criteria set out in Article 3 of Regulation No 141/2000 are no longer met in the MA procedure for a designated orphan medicinal product, only the Commission is empowered to withdraw that designation by adopting a legal decision. However, that decision must be adopted by the Commission ‘before’ the MA is granted, which does not mean that that decision cannot form part of the Commission decision granting or amending the MA for the medicinal product concerned. Indeed, there is nothing in Regulation No 141/2000 or EU legislation which prohibits the Commission from adopting a single implementing decision which at the same time provides for the prior withdrawal of the orphan designation of a medicinal product and the grant of an MA for that same product (see, to that effect, judgment of 22 January 2015, Teva Pharma and Teva Pharmaceuticals Europe v EMA, T‑140/12, EU:T:2015:41, paragraph 53).

116 In the present case, a decision to withdraw the orphan designation of Elotuzumab was adopted by the Commission. In the first place, that medicinal product was removed from the Community Register of orphan medicinal products, which means that a decision concluding that Elotuzumab no longer met the criteria for orphan designation had been taken. In the second place, as the applicant has essentially accepted, in the context of measures of organisation of procedure, that decision was included, by implication, in the Commission’s express decision of 11 May 2016 granting an MA for Empliciti (Elotuzumab), which specifically refers to the COMP opinion of 8 April 2016. As is apparent from paragraph 115 above, there is nothing to prevent the Commission from adopting a single implementing decision which, in the same instrument, provides for both the prior withdrawal of the orphan designation of Elotuzumab and the grant of an MA for Empliciti (Elotuzumab).

117 However, even if the decision to withdraw the orphan designation may form part of the decision granting or amending the MA, together in one and the same instrument, that does not mean that the withdrawal decision may take the form of an implied decision.

118 As regards the designation procedure, Article 5(8) of Regulation No 141/2000, read in the light of the 2003 Communication from the Commission, requires the Commission to adopt a legal decision within 30 days of receipt of the COMP opinion. Furthermore, that communication states that removal from the Community Register of orphan medicinal products must follow the same procedure as that which resulted in the designation, that is, a procedure whereby the COMP issues a scientific opinion, followed by a legal decision by the Commission. It follows that as the decision granting the initial designation, in the present case the Commission’s implementing decision of 9 August 2012, takes an express form, so must the decision withdrawing that designation, so that the withdrawal decision must also take an express form.

119 In addition, in order to ensure that the persons affected by the measures concerned enjoy legal certainty, an express measure granting a designation may be revoked only by a withdrawal measure adopted in the same express form.

120 It follows that a decision withdrawing orphan designation must necessarily take an express form and cannot therefore be made by way of an implied decision.

121 In the present case, by failing to adopt the decision withdrawing the orphan designation of Elotuzumab in an express form, the Commission failed to fulfil its duty to comply with the formal requirements for the adoption of the acts concerned in the procedure for the withdrawal of the designation at issue and, in particular, the duty laid down in Article 5(8) of Regulation No 141/2000, read in the light of the 2003 Communication from the Commission.

122 However, that finding is not sufficient to lead to the annulment of the decision at issue.

123 Bearing in mind the circumstances of the case, if the decision at issue had taken an express form, that would not in any way have altered the content of the decision. It follows that a new, express decision would simply rectify the procedural defect established above but would not in any way alter the substance of the decision at issue, as the Commission followed the COMP opinion of 8 April 2016, which sets out the grounds for the withdrawal of the orphan designation in question, and supports the withdrawal in the present action. It should be noted in that regard that, according to case-law, applicants have no legitimate interest in the annulment of a decision on the ground of a procedural defect where annulment of the decision can only lead to the adoption of another decision identical in substance to the decision annulled (see, by analogy, judgment of 3 December 2003, Audi v OHIM (TDI), T‑16/02, EU:T:2003:327, paragraph 97 and the case-law cited).

124 Moreover, it should be noted that the procedural defect established did not infringe the applicant’s rights of defence. The applicant participated actively in the procedure for the re-evaluation of the designation criteria in question before the EMA. It was fully aware in that connection of the provisional COMP opinion of 18 February 2016, to which the applicant replied in detail, and of the final COMP opinion of 8 April 2016. Thus, the applicant was fully aware of and understood the reasons for the withdrawal of the designation at issue, since it has also been able to conduct a proper defence of its position before the Court, as is clear from its arguments, which are very detailed and particularly thorough, as set out, in particular, in the first plea in law.

125 The Court therefore finds that the applicant has no legitimate interest in the annulment of the decision at issue, which is unlawful only in so far as it entailed a procedural defect, and the annulment of that decision would simply lead to the adoption of another decision identical in substance.

127 It follows from all the foregoing that the three pleas examined must be rejected in their entirety and the action therefore dismissed in its entirety.

128 Under Article 135(2) of the General Court’s Rules of Procedure, the Court may order a party, even if successful, to pay some or all of the costs, if this appears justified by the conduct of that party, including before the proceedings were brought, especially if he has made the opposite party incur costs which the Court holds to be unreasonable or vexatious.

129 In the present case, as is clear from paragraph 121 above, the Commission failed to fulfil its duty to comply with the formal requirements for the adoption of the acts concerned in the procedure for the withdrawal of the orphan designation. Furthermore, the Commission raised a plea of inadmissibility on the ground that the applicant had failed to identify the decision at issue in the application, even though the Commission had contributed to the uncertainty attaching to that point. Against that background, it should be recalled that the Court was required to adopt a measure of organisation of procedure in order to obtain clarification in that regard. In the light of those circumstances, the Court considers that it is appropriate to order the Commission to pay all the costs of the proceedings, including those incurred by the applicant and the EMA.

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You are here: BAILII >> Databases >> Court of Justice of the European Communities (including Court of First Instance Decisions) >> Bristol-Myers Squibb Pharma v Commission and EMA (Public health - Orphan medicinal products - Judgment) [2018] EUECJ T-329/16 (05 December 2018) URL: http://www.bailii.org/eu/cases/EUECJ/2018/T32916.html Cite as: [2018] EUECJ T-329/16, ECLI:EU:T:2018:878, EU:T:2018:878

Court of Justice of the European Communities (including Court of First Instance Decisions)