JUDGMENT OF THE COURT (Third Chamber)
22 June 2023 (*)
(Appeal – Public health – Medicinal products for human use – Regulation (EC) No 726/2004 – Refusal of a marketing authorisation for the medicinal product for human use – Aplidin – plitidepsin – European Medicines Agency (EMA) – Impartiality of experts from a scientific advisory group (SAG) – Policy of the European Medicines Agency on the handling of competing interests of scientific committees’ members and experts – Concept of ‘pharmaceutical company’ – Scope of the exclusion for ‘research organisations’ – Concept of ‘rival products’)
In Joined Cases C‑6/21 P and C‑16/21 P,
TWO APPEALS under Article 56 of the Statute of the Court of Justice of the European Union, lodged on 7 January 2021,
Federal Republic of Germany, represented initially by J. Möller and S. Heimerl, and subsequently by J. Möller and P.-L. Krüger, acting as Agents (C‑6/21 P),
appellant,
supported by:
Kingdom of the Netherlands, represented by M.K. Bulterman, J. Langer and C.S. Schillemans, acting as Agents,
European Medicines Agency (EMA), represented by S. Drosos, H. Kerr and S. Marino, acting as Agents,
interveners in the appeal,
the other parties to the proceedings being:
Pharma Mar SA, established in Colmenar Viejo (Spain), represented by M. Merola and V. Salvatore, avvocati,
applicant at first instance,
European Commission, represented by L. Haasbeek and A. Sipos, acting as Agents,
defendant at first instance,
and
Republic of Estonia, represented by N. Grünberg, acting as Agent (C‑16/21 P),
appellant,
supported by:
Federal Republic of Germany, represented initially by J. Möller and S. Heimerl, and subsequently by J. Möller and D. Klebs, and, lastly, by J. Möller and P.-L. Krüger, acting as Agents,
Kingdom of the Netherlands, represented by M.K. Bulterman, J. Langer and C.S. Schillemans, acting as Agents,
European Medicines Agency (EMA), represented by S. Drosos, H. Kerr and S. Marino, acting as Agents,
interveners in the appeal,
the other parties to the proceedings being:
Pharma Mar SA, established in Colmenar Viejo, represented by M. Merola and V. Salvatore, avvocati,
applicant at first instance,
European Commission, represented by L. Haasbeek and A. Sipos, acting as Agents,
defendant at first instance,
THE COURT (Third Chamber),
composed of K. Jürimäe, President of the Chamber, M. Safjan, N. Piçarra, N. Jääskinen and M. Gavalec (Rapporteur), Judges,
Advocate General: J. Richard de la Tour,
Registrar: M. Longar, Administrator,
having regard to the written procedure and further to the hearing on 12 October 2022,
after hearing the Opinion of the Advocate General at the sitting on 12 January 2023,
gives the following
Judgment
1 By their respective appeals, the Federal Republic of Germany and the Republic of Estonia ask the Court of Justice to set aside the judgment of the General Court of the European Union of 28 October 2020, Pharma Mar v Commission (T‑594/18, not published, ‘the judgment under appeal’, EU:T:2020:512), by which the latter annulled Commission Implementing Decision C(2018) 4831 final of 17 July 2018, refusing marketing authorisation (‘MA’) for ‘Aplidin – plitidepsin’ (‘the decision at issue’), a medicinal product for human use, under 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) as amended by Regulation (EU) No 1027/2012, of the European Parliament and of the Council, of 25 October 2012 (OJ 2012 L 316, p. 38) (‘Regulation No 726/2004’).
Legal context
Regulation No 726/2004
2 Recitals 7, 8 and 19 of Regulation No 726/2004 state:
‘7. Experience gained since the adoption of Council Directive 87/22/EEC of 22 December 1986 on the approximation of national measures relating to the placing on the market of high-technology medicinal products, particularly those derived from biotechnology [(OJ 1987 L 15, p. 38)] has shown that it is necessary to create a centralised authorisation procedure that is compulsory for high-technology medicinal products, particularly those resulting from biotechnical processes, in order to maintain the high level of scientific evaluation of these medicinal products in the European Union and thus to preserve the confidence of patients and the medical professions in the evaluation. … This approach should be maintained, particularly with a view to ensuring the effective operation of the internal market in the pharmaceutical sector.
8. With a view to harmonising the internal market for new medicinal products, this procedure should also be made compulsory for orphan medicinal products …
…
19. The chief task of the [European Medicines] Agency [(‘the Agency’ or ‘the EMA’)] should be to provide Community institutions and Member States with the best possible scientific opinions so as to enable them to exercise the powers regarding the authorisation and supervision of medicinal products conferred on them by community legislation in the field of medicinal products. Only after a single scientific evaluation procedure addressing the quality, safety and efficacy of high-technology medicinal products has been conducted by the Agency, applying the highest possible standards, should [MA] be granted by the Community, and this should be done by means of a rapid procedure ensuring close cooperation between the Commission and Member States.’
3 In the words of Article 9(1) and (2) of that regulation:
‘1. The Agency shall forthwith inform the applicant if the opinion of the Committee for Medicinal Products for Human Use is that:
(a) the application does not satisfy the criteria for authorisation set out in this Regulation;
…
2. Within 15 days after receipt of the opinion referred to in paragraph 1, the applicant may give written notice to the Agency that he wishes to request a re-examination of the opinion …’
4 Title IV of Regulation No 726/2004, entitled ‘The European Medicines Agency – Responsibilities and administrative structure’, includes a Chapter 1, itself entitled ‘Tasks of the agency’, comprising Articles 55 to 66 of that same regulation.
5 Article 56(1) and (2) of Regulation No 726/2004 states:
‘1. The Agency shall comprise:
(a) the Committee for Medicinal Products for Human Use, which shall be responsible for preparing the opinion of the Agency on any question relating to the evaluation of medicinal products for human use;
…
(c) the Committee on Orphan Medicinal Products;
…
(da) the Committee for Advanced Therapies;
…
2. The committees referred to in paragraph 1(a) to (da) may each establish standing and temporary working parties. The committees referred to in paragraph 1(a) and (b) may establish scientific advisory groups in connection with the evaluation of specific types of medicinal products or treatments, to which the committee concerned may delegate certain tasks associated with drawing up the scientific opinions referred to in Articles 5 and 30.
When establishing working parties and scientific advisory groups, the committees shall in their rules of procedures referred to in Article 61(8) provide for:
(a) the appointment of members of these working parties and scientific advisory groups on the basis of the lists of experts referred to in the second subparagraph of Article 62(2); and
(b) consultation of these working parties and scientific advisory groups.’
6 Article 57(1) of Regulation No 726/2004 provides:
‘The Agency shall provide the Member States and the institutions of the Community with the best possible scientific advice on any question relating to the evaluation of the quality, safety and efficacy of medicinal products for human or veterinary use which is referred to it in accordance with the provisions of Community legislation relating to medicinal products.
…’
7 Article 62 provides, in particular, in paragraphs 1 and 2:
‘1. Where, in accordance with this Regulation, any of the Committees referred to in Article 56(1) is required to evaluate a medicinal product for human use, it shall appoint one of its members to act as rapporteur, taking into account existing expertise in the Member State. The Committee concerned may appoint a second member to act as co-rapporteur.
…
When consulting the scientific advisory groups referred to in Article 56(2), the Committee shall forward to them the draft assessment report(s) drawn up by the rapporteur or the co-rapporteur. The opinion issued by the scientific advisory group shall be forwarded to the chairman of the relevant Committee in such a way as to ensure that the deadlines laid down in Article 6(3) and Article 31(3) are met.
The substance of the opinion shall be included in the assessment report published pursuant to Article 13(3) and Article 38(3).
If there is a request for re-examination of one of its opinions where this possibility is provided for in Union law, the Committee concerned shall appoint a different rapporteur and, where necessary, a different co-rapporteur from those appointed for the initial opinion. The re-examination procedure may deal only with the points of the opinion initially identified by the applicant and may be based only on the scientific data available when the Committee adopted the initial opinion. The applicant may request that the Committee consult a scientific advisory group in connection with the re-examination.
2. Member States shall transmit to the Agency the names of national experts with proven experience in the evaluation of medicinal products for human use who, taking into account Article 63(2), would be available to serve on working parties or scientific advisory groups of any of the Committees referred to in Article 56(1), together with an indication of their qualifications and specific areas of expertise.
The Agency shall keep an up-to-date list of accredited experts. The list shall include the experts referred to in the first subparagraph and other experts appointed directly by the Agency. The list shall be updated.’
8 Pursuant to Article 63(2) of that regulation:
‘Members of the Management Board, members of the committees, rapporteurs and experts shall not have financial or other interests in the pharmaceutical industry which could affect their impartiality. They shall undertake to act in the public interest and in an independent manner, and shall make an annual declaration of their financial interests. All indirect interests which could relate to this industry shall be entered in a register held by the Agency which is accessible to the public, on request, at the Agency’s offices.
The Agency’s code of conduct shall provide for the implementation of this Article with particular reference to the acceptance of gifts.
Members of the Management Board, members of the committees, rapporteurs and experts who participate in meetings or working groups of the Agency shall declare, at each meeting, any specific interests which could be considered to be prejudicial to their independence with respect to the items on the agenda. These declarations shall be made available to the public.’
Regulation (EC) No 141/2000
9 Recital 7 of 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) states:
‘ … orphan medicinal products should therefore be submitted to the normal evaluation process; …’.
The EMA Code of Conduct
10 The European Medicines Agency Code of Conduct in the version of 16 June 2016 (EMA/385894/2012 rev. 1.) (‘the EMA Code of Conduct’), provides, in section 2.3.3:
‘For members of the Management Board or Scientific Committees, rapporteurs and experts as well as EMA staff involvement in the Agency’s activities is subject to the availability of a signed declaration of interests form and an assessment of the declared interests. The restrictions that will apply in terms of the individual’s activities in the context of the EMA’s role and responsibilities will depend on the specific individual’s competing interest and their particular role. The details of the relevant restrictions are set out in the EMA policy documents.’
The EMA policy
11 The European Medicines Agency policy on the handling of competing interests of scientific committees’ members and experts, in the version of 6 October 2016 (EMA/626261/2014, Rev. 1, ‘the EMA policy’), contains a section 3.2.2. entitled ‘Other definitions’, which defines the concept of ‘pharmaceutical company’ in the following manner:
‘“Pharmaceutical company” shall mean: any legal or natural person whose focus is to research, develop, manufacture, market and/or distribute medicinal products. For the purpose of this policy, the definition includes companies to which activities relating to the research, development, manufacturing, marketing and maintenance of medicinal products (which might also be carried out in house) are outsourced on a contract basis.
In this regard CROs [clinical research organisations] or consultancy companies providing advice or services relating to the above activities, fall under the definition of a pharmaceutical company.
Legal or natural persons which do not fall within the scope of the above definition but (i) control (i.e. own a majority stake in, or otherwise exercise a significant influence in the decision-making processes of the relevant pharmaceutical company), (ii) are controlled by or (iii) are under common control of a pharmaceutical company, shall be considered as pharmaceutical companies for the purposes of this policy.
Independent researchers and research organisations including universities and learned societies are excluded from the scope of the present definition.’
12 Section 4.1. of the EMA policy, entitled ‘Objectives of the policy’, provides as follows:
‘The main objective of the policy is to ensure that the scientific committees’ members and the experts participating in the Agency’s activities have no interests in the pharmaceutical industry which could affect their impartiality, as per the requirements of EU legislation. This has to be balanced with the need to secure the best (specialist) scientific expertise for the evaluation and surveillance of medicinal products for human and veterinary use. It is, therefore, of utmost importance to strive for the optimal balance between the cooling-off period for the declared interests versus maintaining the experts’ knowledge.
In order to achieve this objective and to strike the aforementioned balance the focus will first be on the nature of the declared interest before determining the length of time any restrictions will apply.’
13 Under section 4.2.1.2 of that policy, entitled ‘Restricting involvement in the Agency’s activities’:
‘Levels of restriction and timeframes
– Involvement of the individual in the Agency’s activities is restricted taking into account three factors: the nature of the declared interest, the timeframe during which such interest occurred, as well as the type of activity. The following methodology applies: first the nature of the declared interest within the frame of the specific Agency activity will be looked at, before determining the length of time any restrictions will apply.
– As a general rule, current … employment with a pharmaceutical company or current financial interests in pharmaceutical industry are incompatible with involvement in the Agency’s activities. One exception to this general rule relates to the concept of expert witness. Current financial interests are compatible with this concept.
– The requirements for membership of decision-making bodies (i.e. scientific committees) are stricter than for advisory bodies (i.e. SAGs and ad hoc expert groups).
– The requirements are also stricter for chairpersons/vice-chairpersons of the scientific committees compared to the chairpersons/vice-chairpersons of other fora and compared to the members of the scientific committees and the other fora. Likewise the requirements are stricter for rapporteurs (or equivalent leading/co-ordinating role) and formally appointed peer reviewers compared to the other members of the scientific fora.
– The timeframe to be considered depending on the declared direct or indirect interest is either current, or within the past 3 years, or in certain cases, … for a longer period …
– …
Specific case of rival products
For the specific case of rival products (formerly referred to as competitor products) a two tier approach is applied:
– The concept of rival products relates to those situations where there are only a very small number (1 to 2) of rival products. The same would apply for the brand leader when a generic product is under consideration;
– For broad indications, since many products are authorised for the same indication, the existing volume of competition dilutes adequately potential interests.
In situations characterised by only a very small number of rival products as specified above, consequences will relate to the (vice)-chairpersons of the scientific committees and the working parties, as well as the rapporteurs or other members in a leading/co-ordinating role, or formally appointed peer reviewers.’
Background to the dispute
14 The background to the dispute is set out in paragraphs 1 to 11 of the judgment under appeal and may be summarised as follows.
15 Pharma Mar SA is a company operating in the oncology research sector. On 16 November 2004, it obtained, in accordance with Regulation No 141/2000, designation of the medicinal product Aplidin, the active substance of which is plitidepsin, as an orphan medicinal product for the treatment of multiple myeloma, a serious cancer of the bone marrow.
16 On 21 September 2016, Pharma Mar, pursuant to Article 4 of Regulation No 726/2004, submitted to the EMA a MA application for Aplidin. That application for MA related to the following indication: ‘in combination with dexamethasone for the treatment of relapsed/refractory multiple myeloma in adult patients who have received at least three prior regimens including bortezomib, and either lenalidomide or thalidomide’.
17 On 14 December 2017, the EMA’s Committee for Medicinal Products for Human Use (‘the CHMP’) issued an opinion recommending that the European Commission reject the application for MA for Aplidin on the ground that the efficacy and safety of the product were not sufficiently demonstrated and that, therefore, the benefits did not outweigh the risks.
18 On the basis of Article 9(2) of Regulation No 726/2004, Pharma Mar submitted to the EMA, on 3 January 2018, a request for re-examination of the CHMP’s opinion, accompanied by a request for consultation with a scientific advisory group, in accordance with Article 62(1) of that regulation.
19 The re-examination procedure began on 15 February 2018. On 7 March 2018, a meeting was held of the Scientific Advisory Group for Oncology (‘the SAG Oncology’), which consisted of five core members, six additional experts and two patient representatives.
20 On 21 March 2018, Pharma Mar presented its oral submissions before the CHMP. On 22 March 2018, the CHMP upheld its opinion of 14 December 2017 and a draft Commission decision was drawn up rejecting the MA application for Aplidin.
21 On 17 July 2018, the Commission adopted the decision at issue, which includes an annex headed ‘Scientific conclusions and grounds for refusal presented by the EMA’, which is consistent with the CHMP’s opinion.
The action before the General Court and the judgment under appeal
22 By application lodged at the Registry of the General Court on 1 October 2018, Pharma Mar brought an action for annulment of the decision at issue.
23 In support of its action, Pharma Mar put forward five pleas in law. Those please alleged the breach, first, of the obligation requiring impartial examination of the application for MA for Aplidin by the members of the SAG Oncology, second, of the principle of good administration, third, of Article 12 of Regulation No 726/2004 and breach of the principle of equal treatment, fourth, of the duty to state reasons; and, fifth, of the rights of the defence.
24 The first plea in law comprised two parts. In the first part of that plea, Pharma Mar disputed the lack of impartiality and, more specifically, the participation in the vote of two experts from the SAG Oncology (together, ‘the two experts’). It contended that they should have been excluded from the vote since they had declared interests that are incompatible with an impartial assessment of the application for MA for Aplidin. Pharma Mar referred, first, to a professor (‘the first expert’), who was vice-president of the SAG Oncology and one of the five core members of that SAG. That first expert was employed by a university institute (‘the Institute’), a renowned educational establishment in the medical field. According to Pharma Mar, the Institute exercises a significant influence over the university hospital in which it is located over a professional clinical research centre, which should be classified as clinical research organisations and, therefore, treated as pharmaceutical companies, pursuant to section 3.2.2. of the EMA policy. Pharma Mar referred, second, to another individual, also a professor and employee of the Institute (‘the second expert’), who was one of the six additional experts in the SAG Oncology and who had stated that he was involved in the development of rival products to Aplidin.
25 In paragraph 84 of the judgment under appeal, the General Court emphasised the potential influence of the SAG Oncology on the conduct and outcome of the procedure for MA for Aplidin, as well as the important role played within that group by the first expert, in his capacity as chair of the meeting of 7 March 2018. Therefore, owing to the participation of the two experts in the SAG Oncology, their employment relationship with the university hospital and the activities of the second expert in connection with rival medicinal products to Aplidin, the General Court considered that the procedure which led to the adoption of the decision at issue did not provide sufficient guarantees to exclude any legitimate doubt as to possible bias.
26 The General Court considered, in paragraph 85 of the judgment under appeal, that the first part of the first plea must be upheld and the decision at issue must, for that reason, be annulled without the need to adjudicate on the second part of the first plea or the remaining pleas in the application.
Forms of order sought by the parties
27 By its appeal in Case C‑6/21 P, the Federal Republic of Germany claims that the Court of Justice should:
– set aside the judgment under appeal;
– uphold the decision at issue and dismiss the action;
– in the alternative, refer the case back to the General Court; and
– order Pharma Mar to bear the costs.
28 By its appeal in Case C‑16/21 P, the Republic of Estonia claims that the Court should:
– set aside the judgment under appeal; and
– order each of the parties to bear its own costs incurred in respect of the appeal.
29 Pharma Mar contends that the Court should:
– declare that there is no need to rule on the appeals or dismiss them as either inadmissible or unfounded; and
– order the appellants to bear their own costs and the costs that the appeals have caused Pharma Mar to incur.
Procedure before the Court
30 By decision of the President of the Court of Justice of 30 March 2021, Cases C‑6/21 P and C‑16/21 P were joined for the purposes of the written and oral procedure and of the judgment.
31 By decisions of 8 July and 17 September 2021, the President of the Court, in Case C‑6/21 P, granted the Kingdom of the Netherlands and the EMA respectively, leave to intervene in support of the forms of order sought by the Federal Republic of Germany.
32 By decisions of 8 and 9 July and of 17 September 2021, the President of the Court, in Case C‑16/21 P, granted the Kingdom of the Netherlands, the Federal Republic of Germany and the EMA respectively, leave to intervene in support of the form of order sought by the Republic of Estonia.
The appeals
33 In support of its appeal in Case C‑6/21, the Federal Republic of Germany raises four grounds of appeal alleging, first, infringement of the concept of ‘pharmaceutical company’, within the meaning of section 3.2.2 of the EMA policy, second, an incorrect allocation of the burden of proof, third, infringement of the concept of ‘rival product’, within the meaning of section 4.2.1.2 of the EMA policy, in the assessment of the experts’ impartiality, and, fourth, the absence of decisive influence on the part of the second expert.
34 The Republic of Estonia in Case C‑16/21, relies on three grounds of appeal alleging, first, infringement of the concept of ‘pharmaceutical company’ within the meaning of section 3.2.2 of the EMA policy, second, infringement of the concept of ‘rival product’, within the meaning of section 4.2.1.2 of the EMA policy, in the assessment of the experts’ impartiality, and, third, failure to have regard to the role of the experts and their influence on the conclusions of the SAG Oncology.
35 Pharma Mar contends that the appeals brought by the Federal Republic of Germany and the Republic of Estonia are inadmissible and, in the alternative, disputes the grounds of appeal put forward by those Member States in support of their respective appeals.
The plea of inadmissibility of the appeals
36 Pharma Mar submits that the appeals are devoid of purpose and should therefore be declared inadmissible. It follows from the case-law of the Court that, although the Member States and the institutions of the Union do not have to demonstrate a specific interest in bringing an appeal against a decision of the General Court, that appeal must still be capable, if successful, of procuring an advantage for them.
37 In the present case, the judgment under appeal merely requires the EMA to conduct a new re-examination, in accordance with the requirement of impartiality, of the MA application for Aplidin. This is the reason for which both the Commission and EMA had decided not to appeal the judgment under appeal but to focus on the rapid commencement of a new re-examination procedure. Pharma Mar therefore asks the Court to declare of its own motion that there is no need to adjudicate on the appeals, which merely seek to clarify hypothetical questions only likely to arise in future cases.
38 In that regard, as regards the interest in bringing proceedings, it follows from the second and third paragraphs of Article 56 of the Statute of the Court of Justice of the European Union that, irrespective of the fact that it was a party to the proceedings at first instance, a Member State may bring an appeal against any decision of the General Court, even those which do not directly affect it, provided that it does not have to show an interest in order to be able to bring an appeal against them (see, to that effect, judgments of 8 July 1999, Commission v Anic Partecipazioni, C‑49/92 P, EU:C:1999:356, paragraph 171, and of 21 December 2011, France v People’s Mojahedin Organization of Iran, C‑27/09 P, EU:C:2011:853, paragraphs 44 and 45).
39 As regards the lack of purpose, by their respective appeals, the Federal Republic of Germany and the Republic of Estonia seek to have set aside the judgment under appeal, which bases the irregularity of the MA procedure for Aplidin on the lack of objective impartiality of the experts in question. The present appeals seek to recognise the lawfulness of the procedure which led to the refusal of the MA application, which shows, in any event, that they are not devoid of purpose.
40 The plea of inadmissibility raised by Pharma Mar must therefore be rejected.
The first grounds of appeal in Cases C‑6/21 P and C‑16/21 P, alleging infringement of section 3.2.2 of the EMA policy and of Article 41(1) of the Charter
– Arguments of the parties
41 By their first ground of appeal, the Federal Republic of Germany and the Republic of Estonia challenge paragraphs 58 to 65 of the judgment under appeal. They submit that the EMA policy does provide sufficient guarantees to exclude any doubt as to the impartiality of the members of the SAG Oncology, with the result that the General Court misinterpreted and misapplied section 3.2.2 of that policy and, therefore, disregarded the right to good administration guaranteed in Article 41(1) of the Charter of Fundamental Rights of the European Union (‘the Charter’).
42 Those Member States claim that the General Court wrongly equated, in paragraphs 61 and 65 of the judgment under appeal, the university hospital as a whole with a ‘pharmaceutical company’ within the meaning of section 3.2.2 of the EMA policy. It concluded, similarly incorrectly, that the employment relationship which existed between that hospital and some of the SAG Oncology experts automatically placed them in a potential conflict-of-interests situation, such as to give rise to doubts as to their impartiality.
43 Pharma Mar takes the view that this plea is unfounded. That party argues that, even assuming that the EMA does indeed enjoy the alleged discretion to ensure the impartiality of that agency’s experts, the EMA policy does not contain any specific rules relevant to the present case. The EMA therefore never exercised that discretion when it defined its policy. In the present case, the cell therapy centre within the university hospital is involved in the development of a rival product to Aplidin, without a third-party observer being able to easily assess whether objective impartiality is being observed, as that centre is not legally distinct from the university hospital. Furthermore, the Commission has not proven the absence of control between the university hospital and that centre. Pharma Mar contends, moreover, that the case-law of the Court of Justice requires that sufficient guarantees be given to exclude any legitimate doubts as to the existence of a conflict of interest.
– Findings of the Court
44 As a preliminary point, it is necessary to examine the argument raised by Pharma Mar in its response, that, in essence, the EMA policy is irrelevant for the purposes of assessing the impartiality of an expert from the SAG Oncology who declared interests in rival products of orphan medicinal products.
45 In that regard, it should be noted, first of all, that recital 8 of Regulation No 726/2004 clearly states that, with a view to harmonising the internal market for new medicinal products, the centralised EU authorisation procedure should also be made compulsory for orphan medicinal products. Next, it follows from recital 7 of Regulation No 141/2000 that, in order for patients with rare conditions to be entitled to medicinal products whose quality, safety and efficacy are the same as those of other patients, orphan medicinal products should be submitted to the normal evaluation process, in other words, the process laid down in Regulation No 726/2004. Lastly, according to Article 57(1) of that regulation, the EMA is responsible for providing the best possible scientific advice on any question relating to the evaluation of the quality, safety and efficacy of medicinal products for human or veterinary use which is referred to it in accordance with the provisions of Community legislation relating to medicinal products. By its general nature, that wording necessarily includes orphan medicinal products.
46 It follows, as the EMA stated at the hearing, that the EMA policy is a comprehensive document which applies without distinction to all medicinal products, whether they are orphan or not. Thus, contrary to Pharma Mar’s contention, the impartiality of an expert from the SAG Oncology who declared interests in rival products of the orphan medicinal product in question may be assessed having regard to the EMA policy.
47 That said, it is necessary to examine the argument of the Federal Republic of Germany and the Republic of Estonia that the General Court erred in law, in paragraph 61 of the judgment under appeal, by interpreting broadly the concept of ‘pharmaceutical company’ within the meaning of section 3.2.2 of the EMA policy and by thus disregarding the broad discretion conferred on the EMA by the EU legislature to ensure the impartiality of that agency’s experts, as well as the wording of section 3.2.2.
48 In that regard, it should be noted, in the first place, that Regulation No 726/2004 seeks, as is apparent in particular from recitals 7 and 8 thereof, to ensure the effective operation of the internal market in the pharmaceutical sector and to harmonise the internal market for new medicinal products. That is why the EU legislature based that regulation inter alia on Article 95 EC, that provision enabling it to adopt measures for the approximation of the provisions laid down by law, regulation or administrative action in Member States which have as their object the establishment and functioning of the internal market.
49 As the Court has already held, by the expression ‘measures for the approximation’ in Article 95 EC, the authors of the Treaty intended to confer on the EU legislature a discretion, depending on the general context and the specific circumstances of the matter to be harmonised, as regards the most appropriate method of approximation for achieving the desired result, in particular in fields with complex technical features. That discretion may be used in particular to choose the most appropriate harmonisation technique where the proposed approximation requires physical, chemical or biological analyses to be made and scientific developments in the field concerned to be taken into account (judgment of 6 December 2005 in Case C‑66/04 United Kingdom v Parliament and Council, EU:C:2005:743, paragraphs 45 and 46).
50 In the light of the discretion thus conferred on it by Article 95 EC, the EU legislature chose, as regards the requirement of impartiality of the EMA’s experts, to lay down essential criteria in the basic regulation and then to entrust that agency with the task of implementing them. That is the purpose of Article 63 of Regulation No 726/2004, which subjects the members of the Management Board, members of committees, rapporteurs and experts of the EMA to obligations of impartiality and independence, while specifying that the implementation of those requirements is entrusted to the EMA, which is responsible for adopting a code of conduct.
51 The EU legislature thus entrusted the EMA with the task of reconciling, on the one hand, the twofold requirement of impartiality and independence of its experts, as laid down in Article 63(2) of that regulation, and, on the other hand, the public interest, referred to in Article 57(1) of that regulation, relating to the need for the best possible scientific advice on any question relating to the evaluation of the quality, safety and efficacy of medicinal products for human or veterinary use which is referred to it.
52 In the second place, in order to enable the EMA to pursue effectively the objective assigned to it, and in view of the complex technical assessments which it must undertake, the broad discretion conferred on it (see, by analogy, judgment of 18 July 2007, Industrias Químicas del Vallés v Commission, C‑326/05 P, EU:C:2007:443, paragraph 75), manifests itself in particular in the definition of the criteria which must govern the impartiality and independence of the individuals contributing to the preparation of its scientific opinions.
53 In that regard, section 2.3.3 of the EMA Code of Conduct refers, in turn, to that agency’s guidance documents in order to set out in detail the restrictions applicable to members of the Management Board or the Scientific Committees, rapporteurs and experts. Those restrictions, which depend on the activities, role and responsibilities of each of those individuals within the EMA, must be commensurate with their competing interests and the role assigned to them.
54 Thus, the first paragraph of section 4.1. of the EMA policy, which gives effect to Article 57(1) of Regulation No 726/2004, states that ‘the main objective of the policy is to ensure that the scientific committees’ members and the experts participating in the Agency’s activities have no interests in the pharmaceutical industry which could affect their impartiality, as per the requirements of EU legislation. This has to be balanced with the need to secure the best (specialist) scientific expertise for the evaluation and surveillance of medicinal products for human and veterinary use. It is, therefore, of utmost importance to strive for the optimal balance between the cooling-off period for the declared interests versus maintaining the experts’ knowledge’.
55 Furthermore, section 4.2.1.2. of that policy provides that, ‘as general rule, current employment with a pharmaceutical company or current financial interests in pharmaceutical industry are incompatible with involvement in the Agency’s activities. …’
56 In the third place, as is apparent from the wording of section 3.2.2 of the EMA policy, referred to in paragraph 11 above, it is necessary to determine, in a first step, whether a university hospital may be treated in the same way as a ‘research organisation’ and, consequently, be excluded from the scope of the definition of ‘pharmaceutical company’. If so, it will then be necessary to examine, in a second step, whether the fact that a university hospital controls the cell therapy centre, which, it is common ground, is a pharmaceutical company, means that it is deprived of the benefit of that exclusion.
57 On the first point, it follows from the wording of that section that, while the first three subparagraphs define ‘pharmaceutical company’ positively, the last subparagraph thereof excludes from the scope of that definition ‘independent researchers and research institutes, including universities and learned societies’. In the light of the wording used, in particular the expression ‘including’, that list cannot be regarded as being exhaustive.
58 It follows from a purposive interpretation of section 3.2.2 of the EMA policy that university hospitals must be treated in the same way as research organisations.
59 Indeed, first, the name of university hospitals shows the proximity which they have with a university which, for its part, is expressly excluded from the scope of the ‘pharmaceutical company’.
60 Second, as the General Court noted in paragraph 57 of the judgment under appeal, a university hospital has a threefold role of care, education and research. As the Federal Republic of Germany and the Republic of Estonia have argued, universities and university hospitals are dedicated for the most part, and, as a general rule, under the law, to non-profit scientific research in the interest of health, they are bound by a series of strict ethical standards as part of their research and are not involved in the marketing of medicinal products.
61 Third, as the Republic of Estonia, the Kingdom of the Netherlands and the EMA correctly stated both in their written pleadings and at the hearing, the exclusion of university hospitals from the concept of ‘pharmaceutical company’, within the meaning of section 3.2.2 of the EMA policy, helps to strike a balance between the need to carry out, on the one hand, an impartial examination of MA applications for a medicinal product and, on the other hand, a careful and as precise scientific examination as possible of questions which arise during the evaluation of a medicinal product. In order to achieve that balance, it appears necessary, as those parties point out, to authorise the EMA to appoint as experts individuals belonging to the staff of university hospitals since, in accordance with the second paragraph of section 4.2.1.2 of that policy, it cannot appoint in that capacity, except for expert witnesses, individuals employed in the pharmaceutical industry or having current financial interests there.
62 It follows from the foregoing considerations that a university hospital must be excluded from the scope of the concept of ‘pharmaceutical company’ within the meaning of section 3.2.2 of that policy.
63 It is therefore necessary to examine, in a second step, whether the fact that a university hospital controls a pharmaceutical company, in this case the cell therapy centre, leads to the conclusion that that hospital is not covered by that exclusion.
64 According to the fourth and last paragraph of the concept of ‘pharmaceutical company’ defined in section 3.2.2 of the EMA policy, ‘independent researchers and research organisations, including universities and learned societies, are excluded from the scope of the present definition’. Formulated unequivocally, that provision does not provide for any exception to the exclusion for which it provides.
65 The EMA emphasised, in essence, at the hearing, that a university hospital is frequently equipped with a small entity which manufactures medicinal products and meets the criteria for classification as a ‘pharmaceutical company’, either because those medicinal products have a short shelf-life, which presupposes that they can be administered very quickly after they have been manufactured, or because they must be produced from biological material taken from patients. In such a context, the unqualified exclusion of research organisations from the scope of the definition of ‘pharmaceutical company’, within the meaning of section 3.2.2 of the EMA policy, is evidence of the EMA’s intention, in the context of the authorisation granted to it by the EU legislature, as recalled in paragraphs 50 and 51 above, to exclude research organisations from the scope of that definition, and by extension, university hospitals.
66 Furthermore, the application to a university hospital of the criterion of control set out in the third paragraph of the definition of pharmaceutical company would render the exclusion provided for in the fourth paragraph of that definition ineffective. Indeed, that hospital would be entirely deprived of the benefit of that exclusion since it controls an entity meeting the criteria of a pharmaceutical company, regardless of the proportion of its workforce assigned to that entity.
67 To consider that all the staff of a university hospital are employed by a ‘pharmaceutical company’, within the meaning of section 3.2.2 of that policy, would also run against the objective of Article 57(1) of Regulation No 726/2004, read in conjunction with recital 19 thereof, and section 4.1 of that policy, which is to strike an optimal balance between the requirement of impartiality of the scientific committees’ members and the experts participating in the Agency’s activities and the need for scientific advice of the highest possible standard.
68 In the present case, the Republic of Estonia stated at the hearing, relying on the statistics relating to 2021, that such an interpretation would lead to the conclusion that the 4 656 workers employed by the Tartu University Hospital (Estonia), which is the only university hospital of that State, work for a pharmaceutical company, even though only four employees are assigned to the manufacture of medicinal products. The Federal Republic of Germany also stated at the hearing that the largest German university hospital, namely, the Charité Hospital in Berlin, employs 20 900 workers, of which only one hundred, at most, are assigned to the hospital’s commercially oriented manufacturing entities.
69 Thus, the fact of providing for an overall exclusion of university hospital experts from participation in the EMA’s scientific opinions on the ground that such hospitals have, within them, one or more entities capable of constituting pharmaceutical companies, within the meaning of section 3.2.2 of the EMA policy, risks creating a shortage of experts with detailed medical knowledge in certain scientific fields, in particular in relation to orphan medicinal products and advanced medicinal products. According to the documents before the Court, the staff of universities and university hospitals represent the most important part of the network of experts requested by the EMA to give a scientific opinion in the context of the procedure for evaluating an application for MA for a medicinal product.
70 The exclusion from the scope of the concept of ‘pharmaceutical company’, defined in point 3.2.2 of the EMA policy, provided for in the fourth paragraph of that definition, does not, however, apply to entities controlled by a university hospital which themselves satisfy the criteria of a ‘pharmaceutical company’ within the meaning of the first paragraph of that definition.
71 Consequently, individuals employed by an entity controlled by a university hospital or who, more broadly, collaborate with that entity cannot be led to express a scientific opinion for the EMA, if that entity meets the criteria of the concept of ‘pharmaceutical company’, as defined in section 3.2.2 of the EMA policy.
72 An interpretation of that kind is such as to ensure an optimal balance between the requirement of impartiality of the experts involved in the Agency’s activities and the requirement of excellence of the experts called upon.
73 It follows that the General Court erred in law in taking the view in the present case that the university hospital was a ‘pharmaceutical company’, within the meaning of the first paragraph of the definition of those terms set out in section 3.2.2 of the EMA policy, solely because it controlled a cell therapy centre which itself satisfied the criteria of the ‘pharmaceutical company’ within the meaning of that provision.
74 Consequently, the first grounds of appeal in Cases C‑6/21 P and C‑16/21 P, alleging infringement of section 3.2.2 of the EMA policy, must be upheld.
75 Since the first grounds of appeal raised by the Federal Republic of Germany and by the Republic of Estonia have been upheld, the judgment under appeal must be set aside, without it being necessary to examine the other grounds of appeal raised by those parties.
Referral of the case back to the General Court
76 In accordance with the first paragraph of Article 61 of the Statute of the Court of Justice of the European Union, if the appeal is well founded, the Court of Justice may, when setting aside the decision of the General Court, give final judgment in the matter, where the state of the proceedings so permits, or refer the case back to the General Court for judgment.
77 In the present case, since the state of the proceedings does not permit final judgment to be given on the merits, the case must be referred back to the General Court.
Costs
78 Since the case has been referred back to the General Court, the costs relating to the appeal proceedings must be reserved.
On those grounds, the Court (Third Chamber) hereby:
1. Sets aside the judgment of the General Court of the European Union of 28 October 2020, Pharma Mar v Commission (T‑594/18, not published, EU:T:2020:512);
2. Refers Case T‑594/18 back to the General Court of the European Union;
3. Reserves the costs.
Delivered in open court in Luxembourg on 22 June 2023.
A. Calot Escobar | | K. Jürimäe |
Registrar | | President of the Chamber |