Judgment;Abstract;Judgment (extracts) — ECLI:EU:T:2019:334
Date: 2019-05-16
Language of the case: English
Court formation: Seventh Chamber
Subject matter: Public health
Procedure: Action for annulment - unfounded
Origin: France

summary table of 15 June 2016, entitled ‘Availability of trientine in Member States according to COMP members review, EMA/317599/2017’ appended as Annex A.7 to the application, which contains specific and verifiable information, by Member State. 62 Moreover, the COMP is a collective body composed of one member designated by each Member State, three members designated by the Commission to represent patient organisations, three members nominated by the Commission acting on a proposal by the EMA and a Chairman, and one member nominated by the States of the European Economic Area (EEA) (recital 6 of Regulation No 141/2000). The COMP is therefore formed by a college representing all Member States together with patient organisations, thus enabling it to form an opinion on the basis of national experiences acquired by both national regulatory authorities and patient organisations. 63 Consequently, and in the absence of any substantiated argument to the contrary by the applicant, the Court considers that the COMP’s inquiry is of high probative value. 64 Second, as regards the evidence adduced by the applicant before the COMP, the applicant has sought to show that, despite the existence of regulatory pathways for importing the reference product in most Member States, there were ‘logistical and administrative’ obstacles preventing effective access to that product. In that regard, the applicant relied on the results of a survey that it undertook itself on the basis of the replies given by the national medicinal product regulatory agencies of 26 Member States, 18 doctors from 15 Member States and patient associations from 11 Member States. It documented the replies in a summary table, appended as Annex 10 to the application, which places the Member States into three groups, namely those in which availability of the reference product is ‘limited[/absent]’ (7 Member States), those in which availability is ‘moderate’ (4 Member States) and those in which availability is ‘good’ (9 Member States). According to the results of that survey, the availability problems identified in the 11 Member States with ‘limited[/no]’ or ‘moderate’ availability are due to the lack of reimbursement of the reference product and to supply problems. 65 After examining the results of that survey, the COMP reached the conclusion that the survey did not sufficiently show that there were availability problems in respect of the reference product. More specifically, the COMP stated that it could not take account, in the assessment of whether or not there was a significant benefit, of considerations related to lack of reimbursement of the reference product in the Member State of importation. Moreover, according to the COMP, the applicant had not provided any additional evidence capable of proving the existence of objective shortages of supply beyond, on the one hand, the lack of reimbursement in some Member States and, on the other hand, the administrative burden entailed by having to arrange importation. 66 As regards the first type of obstacle, namely obstacles arising from lack of reimbursement of the reference product in the Member State of importation, it should be borne in mind that the reimbursement of a medicinal product by the health systems of the Member States falls within the exclusive competence of the Member States. Thus, the fact that the reference product is authorised only in one Member State does not necessarily mean that it is therefore excluded from any reimbursement by the national health system of the Member State of importation. By way of example, it is apparent from the COMP’s inquiry, mentioned in paragraph 58 above, that the reference product is reimbursed in Germany. 67 Moreover, as the applicant conceded at the hearing, nor does obtaining a marketing authorisation at EU level mean that Cuprior would be reimbursed under national health schemes. Furthermore, the applicant does not provide any material capable of showing that Cuprior would probably be reimbursed by national health systems, or to what extent, once a marketing authorisation at EU level has been obtained for it. 68 As regards the second type of obstacle, on which the applicant relies, namely obstacles of an ‘administrative or logistical’ nature, it must be stated that the applicant’s arguments in that respect are not sufficiently substantiated. The applicant merely cites some examples, that are set out in its survey, which is referred to in paragraph 64 above, according to which there is a requirement in certain Member States to obtain prior authorisation which must be renewed periodically or according to which there are unspecified delays in the supply of the reference product, without however showing that the manner in which the national importation schemes function imposes an unreasonable administrative burden on the patient in terms of waiting times, costs or steps to be taken, which might jeopardise the effectiveness of those programmes and, hence, the timely supply of the reference product. As was noted in paragraphs 39 and 40 above, the sponsor must establish not only that its medicinal product provides a benefit or contributes to patient care, but also that that benefit is ‘significant’ and that that contribution is ‘major’. 69 Moreover, the information gathered by the applicant in its survey must, in any event, be compared with the information which emerges from the COMP’s inquiry, which, as this Court has stated, is of high probative value (see paragraph 63 above). That inquiry does not refer to any significant obstacle to access to the reference product in the Member States concerned. 70 Third, with respect to the applicant’s arguments that, for 20 to 30% of all patients with Wilson’s disease, the only possible treatment is a trientine-based medicinal product and, for those patients, the lack of such treatment may be fatal, as the evidence referred to in the first indent of paragraph 27 above allegedly shows, it is sufficient to observe that it is not disputed that for certain patients the only possible treatment is a trientine-based treatment and that the lack of such treatment could be fatal. However, the COMP correctly observed that those data do not show that there is a lack of availability in the European Union of the reference product, which is as effective in treating those patients, or that those patients are incorrectly treated. 71 Accordingly, the Court considers that the COMP did not make an error of assessment in finding that the sponsor had not provided sufficient supporting information to establish that there was an availability problem and that patients with Wilson’s disease in the European Union were not correctly treated by means of products which have already been authorised, including by regulatory routes of access in accordance with Article 5(1) of Directive 2001/83. Consequently, the contested decision, which endorses the COMP’s final opinion, is not vitiated by an error of assessment either. 72 The fourth plea must therefore also be rejected as unfounded. The second plea, alleging an error of law or a manifest error of assessment in the application of Article 3(1)(b) of Regulation No 141/2000 73 By its second plea, the applicant claims that the COMP erred in law or committed a manifest error of assessment by finding that Cuprior did not satisfy the requirements laid down in Article 3(1)(b) of Regulation No 141/2000 because the applicant had not established that the insufficient availability of the reference product within the European Union would cause harm to patients. Once the insufficient availability was established in the present case, there was no need to also show that it led to a failure to meet patient needs or caused patient harm. 74 The Commission disputes the applicant’s arguments. 75 It must be stated in that regard that the applicant’s arguments in support of its second plea are based on the premiss that it has demonstrated the insufficient availability of the reference product in the EU and that it cannot be required to show, in addition, that that insufficiency causes patient harm. However, that premiss has not been proved in the present case, as is apparent from the Court’s analysis of the first and fourth pleas. The second plea of the action is therefore ineffective. 76 In any event, as is apparent from paragraph 32 above, in accordance with Article 3(2) of Regulation No 847/2000, the term ‘significant benefit’ means inter alia a ‘major contribution to patient care’. It follows that the expected contribution of the medicinal product in question must always be assessed by reference to the care needed by patients. Thus, if an alleged increase in the availability of a medicinal product does not result in patients’ real needs being met or, conversely, if the current state of supply causes no harm to patients, the assumption of a significant benefit is not established. 77 The second plea must therefore be rejected. The third plea, alleging an error of law and a breach of the principles of protection of legitimate expectations and procedural fairness 78 The applicant claims that, by relying on the Commission notice of 18 November 2016 on the application of Articles 3, 5 and 7 of Regulation No 141/2000 on orphan medicinal products (OJ 2016 C 424, p. 3, ‘the 2016 Notice’), instead of the 2003 Communication, whereas the 2016 Notice was not applicable ratione temporis either to the application for marketing authorisation filed on 7 December 2015, or to the report on the maintenance of the designation as an orphan medicinal product in respect of Cuprior submitted on 20 September 2016, the COMP erred in law and infringed the principles of protection of legitimate expectations and procedural fairness. 79 According to the applicant, first of all, unlike the 2016 Notice, the 2003 Communication expressly recognises that a significant benefit could be based on an increase in supply or availability and that a product that is authorised in all Member States may constitute a significant benefit in comparison with a product that is authorised in only one Member State. Next, by requiring the applicant to establish the existence of ‘patient harm’, the COMP actually applied the 2016 Notice which alone refers to such a requirement. Lastly, the COMP adopted an overly restrictive approach to the evidence that the applicant should adduce to establish ‘objective supply shortages’ or a ‘systematic shortage’, thus disregarding the letter and spirit of the 2003 Communication. By contrast, the COMP should have required only that the applicant establish that the assumptions which resulted in the initial designation of trientine tetrahydrochloride as an orphan medicinal product remain valid and had not changed at the time of the application for marketing authorisation. 80 The Commission disputes the applicant’s arguments. 81 In the first place, as regards the argument alleging the error of law that the COMP allegedly committed by actually applying the 2016 Notice instead of the 2003 Communication, it should be pointed out at the outset that it was the 2003 Communication which was in force on the date of the application triggering the marketing authorisation procedure for Cuprior, filed on 7 December 2015, and at the time of submission of the report on the maintenance of the designation as an orphan medicinal product of that medicinal product, submitted on 20 September 2016. Since the 2016 Notice, which replaces the 2003 Communication, was published in the Official Journal of the European Union on 18 November 2016, the COMP was entitled to take it into consideration only after that date. The 2003 Communication is therefore applicable ratione temporis to the present case. 82 However, the Court notes that the COMP made no reference whatsoever to the 2016 Notice in its final opinion. Moreover, there is nothing to suggest that the COMP applied the 2016 Notice implicitly. 83 According to Section B.5 of the 2016 Notice, significant benefit should not be based on ‘possible increased supply [or] availability due to shortages of existing authorised products or to existing products being authorised in only one or a limited number of Member States. (Exceptions may be made if the sponsor has evidence of patient harm)’. 84 In that regard, first of all, it must be stated that, in its final opinion, the COMP concluded not that significant benefit could not be based on the fact that the reference product was authorised only in one Member State, unless patient harm was proved — which might suggest that the COMP had actually applied the 2016 Notice — but that the applicant had not demonstrated the existence of an availability problem in respect of the reference product. 85 Next, the mere fact that, in its final opinion, the COMP states that the applicant failed to prove the existence of patient harm, a factor referred to in the 2016 Notice, does not mean that the COMP applied that notice, since, as is stated in paragraph 76 above, the term significant benefit is to be assessed, in any event, by reference to the care which patients actually need. 86 Lastly, the applicant’s argument based on the fact that, in a provisional position of 11 April 2017 (document EMA/COMP/453124/2016, appended as Annex A.8 to the application), the COMP mentioned that, ‘in the light of the upcoming changes in the acceptability of the arguments of limited availability in the new “Notice to Applicants” from the European Commission, the committee should discuss if this aspect of major contribution to patient care in this maintenance procedure shall still be accepted’ cannot succeed. In that passage, the COMP does not refer to the 2016 Notice. Moreover, that passage appears in a document which contains only a provisional opinion which merely states that the COMP should further discuss the abovementioned issue and that, therefore, no final position had been adopted in that regard. 87 In any event, by that argument, the applicant is in actual fact suggesting that if the COMP had adhered to the 2003 Communication, the conclusion that it would have reached would have been different. However, as is apparent from the analysis in paragraphs 35 to 71 above, the contested decision is not vitiated by any error of law and of assessment as regards the interpretation and application in the present case of the term ‘significant benefit’ within the meaning in particular of the 2003 Communication. Accordingly, the applicant’s argument that the COMP wrongly applied the 2016 Notice instead of the 2003 Communication must be considered ineffective. 88 In the second place, it should be borne in mind that Article 5(12)(b) of Regulation No 141/2000 provides for the possibility of removing a designated orphan medicinal product from the EU Register of Orphan Medicinal Products if it is established before the marketing authorisation is granted that the designation criteria are no longer met. According to Section B.2.1 of the 2003 Communication, ‘the sponsor is requested to inform the [EMA] and to submit a report on the criteria that led to the designation of the product as an orphan medicinal product and updated information on the current fulfilment of these criteria’. Section D.3 of the 2014 Guideline also states that the level of evidence or data required by the COMP at that stage of the procedure will be ‘higher … than at the time of designation’. 89 It follows that the COMP was entitled and was even obliged, to re-examine the designation criteria at the stage of the application for marketing authorisation. At the end of that review, the COMP may reach a conclusion different from that which led it to accept the designation of the medicinal product as an orphan medicinal product. Otherwise, the marketing authorisation procedure would be meaningless. 90 Accordingly, the applicant cannot reasonably complain that the COMP reached a conclusion different from that which it had adopted when it accepted the designation of the product as an orphan medicinal product, particularly since, as is stated in paragraph 88 above, at the stage of the application for marketing authorisation, the level of evidence and data required is higher than at the time of the initial designation. 91 In the third place, as regards the alleged infringement of the principle of protection of legitimate expectations, it should be recalled that the protection of legitimate expectations extends to any person with regard to whom an institution of the European Union has given rise to justified hopes and that a person may not plead a breach of that principle unless the administration has given him precise assurances (see order of 4 July 2013, Menidzherski biznes reshenia, C‑572/11, not published, EU:C:2013:456, paragraph 30 and the case-law cited). 92 In whatever form it is given, information which is precise, unconditional and consistent and comes from authorised and reliable sources constitutes assurances capable of giving rise to such hopes (see judgment of 14 March 2013, Agrargenossenschaft Neuzelle, C‑545/11, EU:C:2013:169, paragraph 25 and the case-law cited). 93 Also according to the case-law, economic operators are not justified in having a legitimate expectation that an existing situation which is capable of being altered by the EU institutions in the exercise of their discretionary power will be maintained (judgment of 29 November 2016, T & L Sugars and Sidul Açúcares v Commission, T‑103/12, not published, EU:T:2016:682, paragraph 150). 94 Neither the COMP nor the Commission had at any time provided the applicant with precise assurances that Cuprior would obtain marketing authorisation or that it would be maintained on the list of orphan medicinal products. In particular, the 2015 designation decision was not capable of giving rise to a legitimate expectation on the part of the applicant that that designation would necessarily be followed by the maintenance of such a designation for the medicinal product at issue and by the award of marketing authorisation. 95 Lastly, since the applicant puts forward no independent argument in support of the complaint alleging breach of the principle of ‘procedural fairness’, it is not necessary to respond separately to that complaint. In any event, it should be pointed out that the applicant was afforded the opportunity to submit its observations on all the matters that the COMP had indicated to be relevant prior to the adoption of the final opinion. 96 Consequently, the third plea must be rejected as unfounded. 97 In the light of all the foregoing, the action must be dismissed in its entirety. Costs 98 Under Article 134(1) of the Rules of Procedure of the General Court, 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 applicant has been unsuccessful, it must be ordered to pay the costs, including those incurred in the proceedings for interim measures, in accordance with the form of order sought by the Commission. On those grounds, THE GENERAL COURT (Seventh Chamber) hereby: 1. Dismisses the action; 2. Orders GMP-Orphan (GMPO) to pay the costs, including those incurred in the proceedings for interim measures. Tomljenović Bieliūnas Kornezov Delivered in open court in Luxembourg on 16 May 2019. E. Coulon V. Tomljenović Registrar President * Language of the case: English. 1 This judgment is published in extract form.