CELEX: 62009TJ0052
Medicinal products for human use
Authorisation to place a medicinal product on the market
Regulation (EC) No 1901/2006
Application for a waiver from the obligation to submit a paediatric investigation plan
Rejection by the EMA
Misuse of powers

Legal context

Directive 2001/83
Articles 6 and 8 of Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community
code relating to medicinal products for human use (OJ 2001 L 311, p. 67), as amended inter alia by Regulation (EC) No 1901/2006
of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation
(EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004 (OJ 2006 L 378, p. 1) and by
Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 (OJ 2004 L 136, p. 34), provide:
‘Article 6
1.      No medicinal product may be placed on the market of a Member State unless a marketing authorisation has been issued by the
competent authorities of that Member State in accordance with this Directive or an authorisation has been granted in accordance
with Regulation (EC) No 726/2004, read in conjunction with Regulation (EC) No 1901/2006 …
Article 8
1.      In order to obtain an authorisation to place a medicinal product on the market … an application shall be made to the competent
authority of the Member State concerned.
…
3.      The application shall be accompanied by the following particulars and documents, submitted in accordance with Annex I:
…
(e)      therapeutic indications, contra-indications and adverse reactions;
…
(i)      Results of:
–        pharmaceutical (physico-chemical, biological or microbiological) tests,
–        pre-clinical (toxicological and pharmacological) tests,
–        clinical trials.
…’

Regulation No 726/2004
Article 3 of 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 No 1901/2006, provides:
‘Article 3
1.      No medicinal product appearing in the Annex may be placed on the market within the Community unless a marketing authorisation
has been granted by the Community in accordance with the provisions of this Regulation.
2.      Any medicinal product not appearing in the Annex may be granted a marketing authorisation by the Community in accordance with
the provisions of this Regulation, if:
(a)      the medicinal product contains a new active substance which, on the date of entry into force of this Regulation, was not authorised
in the Community …’.

Regulation No 1901/2006
Articles 1, 2, 3, 6, 7, 11, 13, 15 and 16 of Regulation No 1901/2006 read as follows:
‘Article 1
This Regulation lays down rules concerning the development of medicinal products for human use in order to meet the specific
therapeutic needs of the paediatric population, without subjecting the paediatric population to unnecessary clinical or other
trials and in compliance with Directive 2001/20/EC.
Article 2
In addition to the definitions laid down in Article 1 of Directive 2001/83/EC, the following definitions shall apply for the
purposes of this Regulation:
(1)      “paediatric population” means that part of the population aged between birth and 18 years;
(2)       “paediatric investigation plan” means a research and development programme aimed at ensuring that the necessary data are generated
determining the conditions in which a medicinal product may be authorised to treat the paediatric population;
…
Article 3
1.      ... [A] Paediatric Committee shall be established within the European Medicines Agency set up under Regulation (EC) No 726/2004,
hereinafter “the Agency”. …
Article 6
1.      The tasks of the Paediatric Committee shall include the following:
(a)      to assess the content of any paediatric investigation plan for a medicinal product submitted to it in accordance with this
Regulation and formulate an opinion thereon;
(b)      to assess waivers and deferrals and formulate an opinion thereon;
…
2.      When carrying out its tasks, the Paediatric Committee shall consider whether or not any proposed studies can be expected to
be of significant therapeutic benefit to and/or fulfil a therapeutic need of the paediatric population. The Paediatric Committee
shall take into account any information available to it, including any opinions, decisions or advice given by the competent
authorities of third countries.
Article 7
1.      An application for marketing authorisation under Article 6 of Directive 2001/83/EC in respect of a medicinal product for human
use which is not authorised in the Community at the time of entry into force of this Regulation shall be regarded as valid
only if it includes, in addition to the particulars and documents referred to in Article 8(3) of Directive 2001/83/EC, one
of the following:
(a)      the results of all studies performed and details of all information collected in compliance with an agreed paediatric investigation
plan;
(b)      a decision of the Agency granting a product-specific waiver;
(c)      a decision of the Agency granting a class waiver pursuant to Article 11;
(d)      a decision of the Agency granting a deferral.
For the purposes of point (a), the decision of the Agency agreeing the paediatric investigation plan concerned shall also
be included in the application.
…
Article 11
1.      Production of the information referred to in point (a) of Article 7(1) shall be waived for specific medicinal products or
for classes of medicinal products, if there is evidence showing any of the following:
…
(b)      that the disease or condition for which the specific medicinal product or class is intended occurs only in adult populations;
…
2.      The waiver provided for in paragraph 1 may be issued with reference either to one or more specified subsets of the paediatric
population, or to one or more specified therapeutic indications, or to a combination of both.
…
Article 13
1.      The applicant may, on the grounds set out in Article 11(1), apply to the Agency for a product-specific waiver.
…
Article 15
1.      Where the intention is to apply for a marketing authorisation in accordance with Article 7(1)(a) or (d), Article 8 or Article
30, a paediatric investigation plan shall be drawn up and submitted to the Agency with a request for agreement.
2.      The paediatric investigation plan shall specify the timing and the measures proposed to assess the quality, safety and efficacy
of the medicinal product in all subsets of the paediatric population that may be concerned. In addition, it shall describe
any measures to adapt the formulation of the medicinal product so as to make its use more acceptable, easier, safer or more
effective for different subsets of the paediatric population.
Article 16
1.      In the case of the applications for marketing authorisation referred to in Articles 7 and 8 or the applications for waiver
referred to in Articles 11 and 12, the paediatric investigation plan or the application for waiver shall be submitted with
a request for agreement, except in duly justified cases, not later than upon completion of the human pharmaco-kinetic studies
in adults specified in Section 5.2.3 of Part I of Annex I to Directive 2001/83/EC, so as to ensure that an opinion on use
in the paediatric population of the medicinal product concerned can be given at the time of the assessment of the marketing
authorisation or other application concerned.
…’

Background to the dispute
The applicant, Nycomed Danmark ApS, developed an ultrasound echocardiography imaging agent (perflubutane) to be marketed under
the trade mark Imagify.
On 3 March 2008, the applicant applied to the European Medicines Agency (EMA), on the basis of Article 11(1)(b) and Article
13(1) of Regulation No 1901/2006, for a waiver in respect of Imagify from the obligation to submit the results of a paediatric
investigation plan. In support of its application, it stated that that ultrasound imaging agent was designed to diagnose coronary
artery disease that existed only in the adult population. While acknowledging that the physiopathological processes that lead
to the development of coronary artery disease begin in early childhood, it claimed that those diseases have, in children,
only the character of nascent clinical conditions and essentially concern only subjects suffering familial hypercholesterolemia
or type 1 diabetes mellitus. In addition, the applicant emphasised that even in those two populations of high-risk paediatric
patients, the clinical signs and symptoms, such as chest pains, breathlessness or even angina pectoris and myocardial infarction,
do not appear before the onset of adulthood.
According to the applicant’s application, in clinical trials the efficacy and safety of Imagify were compared to those of
the methods currently used to diagnose coronary artery disease. The application also states that the advantage of the diagnostic
technique applied when using Imagify is that it does not involve any radiation exposure and is therefore relatively harmless.
On 8 May 2008, the Paediatric Committee of the EMA (‘the Paediatric Committee’) requested the applicant, by a preliminary
opinion, to modify its waiver application and address the question of the potential benefit of Imagify in paediatric echocardiography.
On 10 July 2008 the applicant indicated that it did not intend to modify its application as requested.
After a meeting with the applicant, the Paediatric Committee adopted its first opinion on 19 September 2008 (‘the first opinion’).
It recommended that the EMA refuse the waiver sought, being of the view that the applicant had, incorrectly, restricted the
scope of its waiver application to the diagnosis of coronary artery disease, when the ultrasound imaging agent to which the
application related could be used in the diagnosis of other diseases.
By letter of 20 October 2008, the applicant lodged a reasoned request that the Paediatric Committee should issue a new opinion.
In that request the applicant pointed out, first, that it was for the applicant to define the scope of the indication for
which marketing authorisation of the medicinal product concerned was requested and, second, that the Paediatric Committee
did not have powers to request amendment of the application.
On 3 November 2008 the applicant was notified of a draft opinion of the Paediatric Committee, which was again unfavourable.
The Paediatric Committee stated first that the ultrasound imaging agent developed by the applicant was designed to identify
myocardial perfusion defects and then, in particular, that such defects could also be caused by diseases which can occur in
children. In that draft opinion, the Paediatric Committee proposed, inter alia, that the applicant should submit, in accordance
with Articles 20 and 21 of Regulation No 1901/2006, a request for deferral of the initiation or completion of the measures
set out in the paediatric investigation plan provided for in Article 15 of that regulation.
By letter of 6 November 2008 the applicant contested the Paediatric Committee’s assessment. On 14 November 2008 the Paediatric
Committee adopted the final version of its second opinion (‘the second opinion’). In that opinion it expressed the view that
a waiver should not be granted. By letter of 19 November 2008 the applicant requested the EMA to reconsider that opinion.
On 28 November 2008 the EMA rejected the applicant’s application for the grant of the waiver sought (‘the contested decision’).
That decision refers to the second opinion of the Paediatric Committee, which is annexed thereto. The second opinion refers,
in its turn, to the summary report annexed to that opinion. That report is in two parts, the first part corresponding to the
first opinion (see paragraph 8 above), while the second part is devoted to a reconsideration of that first opinion.
The applicant was notified of that decision on 2 December 2008.

Procedure and forms of order sought
By application lodged at the Registry of the Court of First Instance (now the ‘General Court’) on 11 February 2009, the applicant
brought the present action.
By separate document lodged at the Court Registry on the same day, the applicant made an application for interim measures,
in which it sought, first, suspension of the effects of the contested decision and, secondly, the adoption of interim measures.
By a separate document lodged at the Court Registry on 18 February 2009, the applicant applied for the case to be decided
under an expedited procedure in accordance with Article 76a of the Rules of Procedure of the General Court. That application
was rejected by decision of the General Court (Fifth Chamber) of 1 April 2009.
By order of the President of the General Court of 24 April 2009, the application for interim measures submitted by the applicant
was dismissed and the costs reserved.
By document lodged at the Court Registry on 13 May 2009, the Portuguese Republic sought leave to intervene in the present
proceedings in support of the form of order sought by the EMA.
By document lodged at the Court Registry on 15 May 2009, the Kingdom of Belgium and the United Kingdom of Great Britain and
Northern Ireland sought leave to intervene in the present proceedings in support of the form of order sought by the EMA.
By documents lodged at the Court Registry on 19 and 20 May 2009, respectively, the French Republic and the Commission of the
European Communities applied for leave to intervene in the present proceedings in support of the form of order sought by the
EMA.
The applications to intervene were served on the parties in accordance with Article 116(1) of the Rules of Procedure.
By order of 9 July 2009, the President of the Fifth Chamber of the Court granted the Portuguese Republic leave to intervene
in support of the form of order sought by the EMA. The Portuguese Republic lodged its statement in intervention on 27 July
2009.
By order of 2 September 2009 the President of the Fifth Chamber of the General Court granted the Kingdom of Belgium, the United
Kingdom, the French Republic and the Commission leave to intervene in support of the form of order sought by the EMA. The
United Kingdom lodged its statement in intervention on 18 November 2009. The Kingdom of Belgium, the French Republic and the
Commission lodged their statements in intervention on 19 November 2009.
The applicant submitted its observations on the statements in intervention on 22 March 2010.
By separate documents lodged at the Court Registry on 22 June and 22 July 2009 the applicant requested, inter alia, confidential
treatment for certain paragraphs of the application, the EMA’s defence and the reply, with regard to all the interveners.
By letter lodged at the Court Registry on 25 September 2009 the United Kingdom objected to the abovementioned requests for
confidential treatment.
By order of 26 March 2010 the President of the Fifth Chamber of the Court rejected the requests for confidential treatment
in so far as they were challenged by the United Kingdom.
The composition of the Chambers of the Court having been altered, the Judge-Rapporteur initially appointed was attached to
the Third Chamber, to which this case was accordingly assigned. Owing to the partial renewal of the Court, the present case
was assigned to a new Judge-Rapporteur sitting in the same Chamber.
The parties presented oral argument and replied to the questions put by the Court at the hearing on 12 July 2011.
The applicant claims that the Court should:
–        annul the contested decision;
–        order the EMA to pay the costs.
The EMA, supported by the Portuguese Republic, the Kingdom of Belgium, the United Kingdom, the French Republic and the Commission,
contends that the Court should:
–        dismiss the application as unfounded;
–        order the applicant to pay the costs.

Substance
The applicant puts forward two pleas in law in support of its action. The first plea alleges incorrect interpretation of the
concept of ‘disease or condition for which the medicinal product is intended’ employed in Article 11(1)(b) of Regulation No
1901/2006. The second plea relates to misuse of powers.

First plea: incorrect interpretation of the concept of ‘disease or condition for which the medicinal product is intended’
employed in Article 11(1)(b) of Regulation No 1901/2006
It should be noted that Article 11(1)(b) of Regulation No 1901/2006, whose interpretation, as proposed by the EMA, is disputed
by the applicant, is contained within a legal framework defined mainly by three normative acts.
First, Directive 2001/83 codified and assembled in a single text the directives on the approximation of provisions laid down
by law, regulation and administrative action relating to medicinal products for human use.
Article 1(2)(a) of Directive 2001/83, as amended by Directive 2004/27, defines a medicinal product as ‘[a]ny substance or
combination of substances presented as having properties for treating or preventing disease in human beings’. Article 1(2)(b)
also defines a medicinal product as ‘[a]ny substance or combination of substances which may be used in or administered to
human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological,
immunological or metabolic action, or to making a medical diagnosis’. A product is a medicinal product if it falls within
either of those definitions which, according to settled case-law, are to be interpreted broadly (see Case C‑84/06
Antroposana and Others
[2007] ECR I‑7609, paragraph 31 and the case-law cited).
Article 6(1) of Directive 2001/83 provides that no medicinal product may be placed on the market of a Member State unless
a marketing authorisation has been issued by the competent authorities of that Member State in accordance with that directive
or an authorisation has been granted in accordance with Regulation No 726/2004, read in conjunction with Regulation No 1901/2006.
Secondly, Regulation No 726/2004 establishes, in particular, a centralised marketing authorisation procedure within the European
Union, applicable inter alia to the medicinal products listed in the annex to that regulation and those containing a new active
substance not authorised in the European Union. The marketing authorisation is to be issued by the Commission, after obtaining
the opinion of the Committee for Medicinal Products for Human Use, which is part of the EMA. Under that procedure, applications
for marketing authorisation are to be submitted to the EMA, which is responsible for coordinating the scientific evaluation
of the quality, safety and efficacy of the medicinal product concerned.
Thirdly, Regulation No 1901/2006 lays down specific rules concerning medicinal products for paediatric use.
At the date on which that regulation was adopted, more than 50% of the medicinal products administered to children in Europe
had not been authorised for such use and had not been subjected to appropriate trials (see opinion of the European Economic
and Social Committee on the ‘Proposal for a Regulation of the European Parliament and of the Council on medicinal products
for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/83/EC and Regulation (EC) No 726/2004’ (OJ 2005
C 267, p. 1), point 2.1).
According to recital 3 in the preamble to Regulation No 1901/2006, problems resulting from the absence of suitably adapted
medicinal products for the paediatric population include inadequate dosage information, which leads to increased risks of
adverse reactions including death, ineffective treatment through under-dosage, non-availability to the paediatric population
of therapeutic advances, suitable formulations and routes of administration, as well as use of magistral or officinal formulations
to treat the paediatric population which may be of poor quality.
Recital 2 in the preamble to Regulation No 1901/2006 states that market forces alone have proven insufficient to stimulate
adequate research into, and the development and authorisation of, medicinal products for the paediatric population.
In that context, recital 4 in the preamble to Regulation No 1901/2006 states that that regulation aims, first, to facilitate
the development and accessibility of medicinal products for use in the paediatric population, secondly, to ensure that such
medicinal products are subject to research of high quality in accordance with ethical rules and are appropriately authorised
for use in the paediatric population and, thirdly, to improve the information available on the use of medicinal products in
the various paediatric populations. That recital states that those objectives should be achieved without subjecting the paediatric
population to unnecessary clinical trials and without delaying the authorisation of medicinal products for other age populations.
In order to achieve those aims, Regulation No 1901/2006 provides a mechanism for compelling pharmaceutical companies to envisage
as a matter of course the possibility of the paediatric use of the medicinal products they develop.
The central element of that mechanism is the paediatric investigation plan, defined in Article 2(2) of Regulation No 1901/2006.
Article 7(1)(a) of Regulation No 1901/2006 provides that an application for authorisation to market a medicinal product must
in principle include the results of all studies performed and details of all information collected in compliance with such
an agreed plan. Thus, an applicant who intends to make an application for marketing authorisation of a medicinal product is
under an obligation to draw up a paediatric investigation plan and submit it to the EMA for approval, in accordance with Article
15(1) of Regulation No 1901/2006.
In order to prevent that mechanism from holding back research and development of new medicinal products, Regulation No 1901/2006
provides, inter alia, for a system of waivers of that obligation, one of which is the contested waiver provided for in Article
11(1)(b) of Regulation No 1901/2006.
Under that article, production of the information referred to in Article 7(1)(a) may be waived for specific medicinal products
or for classes of medicinal products, if there is evidence showing that the disease or condition for which the specific medicinal
product or class of medicinal products is intended occurs only in adult populations. It would be illogical to require a paediatric
investigation plan to be drawn up for a medicinal product intended only for a disease or condition which never occurs in the
paediatric population.
It is in the light of those considerations that it is appropriate to examine the applicant’s argument that the EMA adopted
the contested decision on the basis of an incorrect interpretation of the concept of ‘disease or condition for which the …
medicinal product is intended’, employed in Article 11(1)(b) of Regulation No 1901/2006.
It should be noted, first of all, that it is clear from the definition of the term ‘medicinal product’ given in Article 1(2)(b)
of Directive 2001/83, that ‘medicinal product’ means, inter alia, any substance or combination of substances which may be
used in or administered to human beings with a view to making a medical diagnosis. In that regard, it must be held, as is
apparent moreover from all of the applicant’s arguments, that diagnosis consists in the identification of one or more diseases
or conditions according to their signs.
Admittedly, Regulation No 1901/2006 makes no distinction between medicinal products and therefore, as the applicant correctly
argues, the conditions with respect to obtaining a waiver of the requirement to submit a paediatric investigation plan are
the same for a diagnostic product as they are for other medicinal products. However, diagnostic products are by nature different
from therapeutic products. They are used only indirectly in the treatment of a disease or a condition, since their immediate
objective is to detect the signs of a disease or a condition.
In view of that particular feature of diagnostic products, it must be held that, where the waiver referred to in Article 11(1)(b)
of Regulation No 1901/2006 relates, as in the present case, to such a product, it must be granted if it is established that
the disease or condition for the diagnosis of which the medicinal product or class of medicinal products at issue is intended
occurs only in the adult population.
When read in that way, the provision at issue raises the question of identifying the disease or condition for the diagnosis
of which the medicinal product or products at issue ‘is intended’. In particular, it is a matter of determining whether the
purpose of a medicinal product must be assessed objectively, after taking into consideration merely the properties of that
medicinal product, or whether it corresponds to the diagnostic indication given by the promoter of that product, and is therefore
of a subjective nature.
In the first case, a diagnostic product should be considered to be intended for the diagnosis of any disease or condition
associated with a sign that it is capable of detecting. In the second case, the indication given by the promoter of the product
is binding; a medicinal product cannot be regarded as being intended for the diagnosis of diseases or conditions other than
those corresponding to the indication chosen by its promoter.
As is apparent from the grounds of the contested decision, the decision is based on the first interpretation of the provision
at issue.
In that regard, it should be noted that the contested decision does not contain a separate statement of reasons but refers
to the second opinion which is annexed to it, in accordance with the second sentence of Article 25(5) of Regulation No 1901/2006.
The statement of reasons for that opinion is contained in the summary report annexed to the opinion (see also paragraph 12
above). By making reference to the second opinion, the contested decision clearly followed the reasoning of that opinion.
It must therefore be concluded that the reasons on which the contested decision is based are the same as those of the summary
report.
That report summarises the views of the EMA’s Paediatric Coordinator, the Rapporteur and the Peer Reviewer of the Paediatric
Committee, with whom the other members of that committee were in agreement. Thus, in the part of the report devoted to the
re-examination of the first opinion, the Paediatric Coordinator stated as follows: ‘Echocardiography with [Imagify] is by
the applicant proposed to be a method to reveal myocardial perfusion abnormalities/defects. The possible causes of these abnormalities
can be various heart diseases, which occur both in children and adults. Among those are not only coronary atherosclerosis,
but congenital heart defects, coronary anomalies, cardiomyopathies, coronary problems after surgery for congenital cardiac
defects and acquired coronary problems after vasculitis such as Kawasaki disease. It is well understood that the applicant’s
strategic goal is to obtain marketing authorisation for the specific adult indication of diagnosing coronary artery disease
only, possibly because in adults this is the most frequent cause of myocardial perfusion abnormalities. … As myocardial perfusion
abnormalities do indeed occur in the paediatric population the Regulation does not allow a waiver to be granted on the grounds
that one of the possible underlying diseases, i.e. coronary artery disease, does not occur in children.’ The Rapporteur of
the Paediatric Committee approved that assessment, stating as follows: ‘If this product is beneficial in the adult as claimed
by the company, sooner or later this product will be applied in paediatrics. Indeed, a number of paediatric patients with
myocardial perfusion disturbances might benefit from this technique and thus avoid more invasive techniques.’ The Peer Reviewer
stated in conclusion: ‘This product is a diagnostic to assess myocardial perfusion and there is a possible use in children
to assess myocardial perfusion. A waiver is not appropriate.’
It is thus apparent from the second opinion that the Paediatric Committee considered that Imagify was intended to detect myocardial
perfusion abnormalities. Such abnormalities are not only a sign characteristic of coronary artery disease, but also a sign
of other diseases or conditions, some of which manifest themselves in the paediatric population. Having adopted the first
of the interpretations envisaged in paragraph 52 above, the Paediatric Committee therefore concluded that the applicant’s
waiver application should be rejected.
In that regard, it is necessary to reject the United Kingdom’s view, expressed in its statement in intervention, that the
Paediatric Committee rejected the waiver application on the ground that coronary artery disease, although rare, does occur
in children. Although that fact is indeed mentioned incidentally in the summary report, it is apparent from an overall reading
of the report that the second opinion and hence the contested decision are based on the grounds set out in the preceding paragraph.
Nor is it possible to accept the applicant’s view that the contested decision is based on the incorrect ground that myocardial
perfusion defects are a condition, within the meaning of Article 11(1)(b) of Regulation No 1901/2006, which may occur in children,
whereas in reality they are a sign of various diseases.
The summary report occasionally uses the term ‘condition’ to describe myocardial perfusion defects. However, in the light
of the extracts from the summary report cited in paragraph 56 above, it is clear that the Paediatric Committee and consequently
the EMA, when it adopted the contested decision, were well aware of the fact that myocardial perfusion defects are a sign
of various diseases and not a separate condition, within the meaning of the abovementioned provision. This is adequately demonstrated,
first, by the Peer Reviewer’s statement that ‘there are a number of conditions in children resulting in myocardial perfusion
abnormalities’ and, secondly, by the reference made by the Rapporteur to ‘[t]he condition of myocardial perfusion disturbance’.
It follows that the contested decision is based on the ground stated in paragraph 57 above and not on the ground mentioned
by the applicant in its argument set out in the preceding paragraph.
Whilst, as stated above, the contested decision is based on the first of the interpretations of Article 11(1)(b) of Regulation
No 1901/2006 envisaged in paragraph 52 above, the applicant argues in favour of the second of those interpretations and thus
complains that the EMA based its decision on an incorrect interpretation of the provision concerned. More specifically, the
applicant submits that Article 11(1)(b) of Regulation No 1901/2006 should be interpreted in the light of Article 2(2) and
Articles 7, 8 and 15 of that regulation. It is apparent from a combined reading of those provisions that the paediatric investigation
plan is linked to the therapeutic indication stated in the waiver application.
In order to examine that line of argument, it should be noted in the first place that Article 11(1)(b) of Regulation No 1901/2006
refers to the disease or condition for the treatment (or, in the case of a diagnostic, diagnosis) of which the specific medicinal
product is ‘intended’, without mentioning the word ‘indication’. That difference in terminology argues against the applicant’s
interpretation, especially since the word ‘indication’ is used by that regulation in other contexts; such is the case, for
example, in Article 11(2) of that regulation.
In the second place, taking a teleological approach, it must be observed that the applicant’s view, if it were adopted, would
give pharmaceutical companies the opportunity to circumvent with ease their obligations under Regulation No 1901/2006. In
order to obtain a waiver of those obligations, it would be enough for them to restrict sufficiently the scope of the indication
of the medicinal products they develop. In particular, a company which had designed a medicinal product for detecting a sign
that is characteristic of diseases affecting both the adult and the paediatric populations would need only to propose an indication
excluding the paediatric population from its scope in order to be sure of obtaining a waiver. However, in such a case, the
absence of suitably adapted medicinal products for the paediatric population, at least for diagnosis, would not be overcome,
although that is one of the objectives of Regulation No 1901/2006.
In the third place, the interpretation adopted in the contested decision is consistent with the role and powers conferred
on the Paediatric Committee by Regulation No 1901/2006. According to recital 8 in the preamble to that regulation, that committee
is the only body with ‘expertise and competence in the development and assessment of all aspects of medicinal products to
treat paediatric populations’. Moreover, as provided in the second sentence of Article 6(2) of that regulation, the Paediatric
Committee is to take into account any information available to it, which again argues against the view that it must base its
decision exclusively on the indication stated in the waiver application.
In the fourth place, it should be pointed out that the interpretation adopted in the contested decision in no way means that
the indication stated by the promoter of a medicinal product in his application for waiver of his obligation to submit a paediatric
investigation plan will not be taken into account by the Paediatric Committee and, ultimately, by the EMA when considering
that application. On the contrary, that indication will of necessity constitute the starting point for the Paediatric Committee’s
assessment.
Thus, a waiver applied for will be granted in cases in which the Paediatric Committee finds that the medicinal product in
question makes it possible to diagnose a sign that is attributable only to diseases or conditions having the dual characteristic
of being covered by the indication proposed by the applicant and also existing only in the adult population.
However, unlike the interpretation of the relevant provision advocated by the applicant, the interpretation adopted in the
contested decision allows the Paediatric Committee to establish, by a reasoned opinion based on scientifically-reasoned, objective
evidence, that the diagnostic product at issue permits detection of a sign that may be associated not only with the diseases
or conditions covered by the indication proposed by its promoter, but also with one or more other diseases or conditions which
exist in the paediatric population, in particular. In such a case, the EMA is obliged to reject the waiver application unless
the applicant, under the administrative procedure introduced by Regulation No 1901/2006, manages to rebut that contention,
by demonstrating to the Paediatric Committee, on the basis of objective evidence, that the medicinal product concerned permits
detection only of signs attributable to diseases or conditions that exist only in the adult population.
In the fifth place, it must be observed that the other arguments put forward by the applicant in support of its view are unconvincing.
First, the applicant contends that it is not for the EMA to make the therapeutic indication broader than that envisaged by
an applicant for a waiver. It considers that the indication stated in the application for marketing authorisation can be perfectly
consistent with the indication envisaged in the paediatric investigation plan. Moreover, the authority granting the marketing
authorisation concerned will never – or only in very specific circumstances – broaden the indication proposed by the applicant.
The agreed indication must be based on the data submitted by the applicant, which must be specific to the target population.
The applicant’s line of argument to that effect is the result of confusion between, on the one hand, the indication stated
by the promoter of a medicinal product in its application for a waiver of the obligation to submit a paediatric investigation
plan and, on the other hand, the indication that will subsequently be stated by that promoter in the application for marketing
authorisation of that medicinal product. The applicant, thus, failed to take into account the fact that a waiver application
is submitted at an early stage in the procedure which may ultimately lead to a marketing authorisation being obtained.
It should be noted in that regard that, according to Article 8(3)(e) and Article 11 of Directive 2001/83, which are also applicable
to applications for marketing authorisation provided for in Article 6 of Regulation No 726/2004, such applications must contain
a reference to the (therapeutic or diagnostic) indication in respect of which a marketing authorisation is sought. In accordance
with the second subparagraph of Article 13(1) of Regulation No 726/2004, read in conjunction with Article 21(1) of Directive
2001/83, the granting of a marketing authorisation involves approval of the proposed summary of the product characteristics,
which, according to Article 11(4.1.) of Directive 2001/83, includes the product’s indication. Similarly, Article 26(1) of
Directive 2001/83 states that the marketing authorisation must be refused if it is clear, inter alia, that the risk‑benefit
balance is not favourable. That balance, defined by Article 1(28) and (28a) of that directive, is clearly to be assessed in
the light, inter alia, of the indications in respect of which the marketing authorisation is sought.
Therefore, the (therapeutic or diagnostic) indication of a medicinal product, which has been chosen by its promoter, is decisive,
both as regards the definition of the scope of the preclinical and clinical pharmaceutical trials that have to be conducted
in order to obtain a marketing authorisation, and as regards determination of the rights conferred by such authorisation once
it has been granted.
Although approval of a paediatric investigation plan, for the purpose of Regulation No 1901/2006, or obtaining a waiver of
the obligation to submit such a plan constitutes a prerequisite for the introduction of an application for authorisation to
market a specific medicinal product, the fact remains that such approval or waiver is subject to particular rules governing
procedure and dealing with the substance of the matter. It takes place, moreover, well before the marketing authorisation
procedure begins.
According to Article 16(1) of Regulation No 1901/2006, the paediatric investigation plan or the application for a waiver of
the obligation to submit such a plan must be submitted at an early stage in the development of the product and, in any event,
before the application for marketing authorisation is submitted.
Furthermore, although, as the applicant observes, the standard form to be used when applying, inter alia, for approval of
a paediatric investigation plan or a waiver of the obligation to submit such a plan requires the (therapeutic or diagnostic)
indication of the medicinal product in question to be stated, the indication thus stated will be used only during consideration,
by the Paediatric Committee and, ultimately, by the EMA, of the merits of that application and, as mentioned in paragraph
65 above, will constitute only the starting point for such consideration.
That indication must not, therefore, be confused with the indication which, when the time comes, will be stated by the promoter
of the medicinal product in question in his application for marketing authorisation. Regulation No 1901/2006 contains no provision
authorising the Paediatric Committee to determine, in the context of consideration of an application for a waiver of the obligation
to submit a paediatric investigation plan, the indication that will appear in the marketing authorisation for the medicinal
product in question. Thus, the indication stated in the waiver application is without prejudice to that in respect of which
the person concerned will subsequently apply for marketing authorisation.
Moreover, if, in the event that the waiver application is rejected, the studies provided for in the paediatric investigation
plan are carried out and justify the scope of the indication of a medicinal product initially envisaged being extended to
include the paediatric population, there is nothing to stop the promoter of that medicinal product himself, when submitting
his application for marketing authorisation, from extending the indication of his medicinal product in this way, especially
because such extension would appear to be in his business interests.
The foregoing considerations are not called into question by the applicant’s reference to the Commission Communication – Guideline
on the format and content of applications for agreement or modification of a paediatric investigation plan and requests for
waivers or deferrals and concerning the operation of the compliance check and on criteria for assessing significant studies
(JO 2008 C 243, p. 1).
The applicant cites, more particularly, the first paragraphs of points 2.3, 2.3.1 and 2.3.2 of that communication, which all
contain the word ‘indication’. There is nothing in those paragraphs that suggest that the (therapeutic or diagnostic) indication
stated at the stage of the application for waiver of the obligation to submit a paediatric investigation plan must be the
same as that which will appear in the application for marketing authorisation. On the contrary, in Part 1 ‘Introduction’,
the communication draws a distinction, between, on the one hand, in (c) and (b) respectively, the therapeutic indication as
proposed and as adopted in the paediatric investigation plan, and on the other hand, in (d), the granted therapeutic indication,
which appears in the marketing authorisation.
Lastly, the applicant contends that the paediatric investigation plan must be seen as ancillary to the set of studies required
pursuant to Article 8(3)(i) of Directive 2001/83. It adds that the trials and tests conducted by it or on its behalf in order
to obtain marketing authorisation relate exclusively to the indications for which the product concerned has been developed.
It is sufficient to state in that regard that the argument that the paediatric investigation plan is ancillary is not based
on any of the provisions of Regulation No 1901/2006 and that in any event, in the light of the wording of Article 15(2) of
that regulation, it is by no means excluded that that plan may provide for further studies to be conducted in addition to
those provided for in Article 8(3)(i) of Directive 2001/83.
Secondly, the applicant argues that the exposure of adults to further clinical trials in order for a product to be administered
to children is contrary to the spirit of provisions of European Union law relating to medicinal products. Such trials could
also be considered as violating the principles of the Helsinki Declaration of the World Medical Assembly of June 1964, as
amended, referred to in the second paragraph of Article 3 of Commission Directive 2005/28/EC of 8 April 2005 laying down principles
and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as
the requirements for authorisation of the manufacturing or importation of such products (ΟJ 2005 L 91, p. 13). That provision
states that ‘[c]linical trials shall be conducted in accordance with the Declaration of Helsinki on Ethical Principles for
Medical Research Involving Human Subjects’. Such trials would also be contrary to recital 4 in the preamble to Regulation
No 1901/2006.
It must be observed that any clinical trial provided for in a paediatric investigation plan must be conducted in compliance
with the relevant provisions of European Union law, including the provisions of Directive 2005/28, mentioned above, and Directive
2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and
administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of
clinical trials on medicinal products for human use (OJ 2001 L 121, p. 34), Article 4 of which provides:
‘In addition to any other relevant restriction, a clinical trial on minors may be undertaken only if:
…
(e)      some direct benefit for the group of patients is obtained from the clinical trials on persons able to give informed consent
or by other research methods; additionally, such research should either relate directly to a clinical condition from which
the minor concerned suffers or be of such a nature that it can only be carried out on minors;
…’.
Nothing in those directives, or in the Helsinki Declaration to which the first directive cited above refers, supports the
applicant’s view that the relevant ethical rules prohibit, in all cases, the exposure of adults to clinical trials in order
to obtain benefit for children alone. Likewise, recital 4 in the preamble to Regulation No 1901/2006 contains nothing to support
that view.
Moreover, contrary to what the applicant claims, Article 4(e) of Directive 2001/20 does not necessarily require clinical trials
to be conducted on adults first in order for it later to be possible for them to be carried out on the paediatric population.
That provision envisages, inter alia, the possibility of conducting such trials on the paediatric population where they are
essential to validate data obtained ‘by other research methods’ than trials carried out on adults.
Lastly, whilst accepting that myocardial perfusion defects are not only a sign of coronary artery disease but also a sign
of other diseases or conditions, the applicant maintains that, because such defects are so rare in the paediatric population,
it would not be possible to set up trials and studies that would be statistically reliable.
However, even if that were the case, the fact remains that that would not affect the outcome of the present dispute. The mechanism
of the paediatric investigation plan, introduced by Regulation No 1901/2006, covers (with the exception of those categories
of medicinal products listed exhaustively in Article 9 thereof) all medicinal products for paediatric use, with the aim of
facilitating their development and accessibility. That aim would not be fully achieved if a medicinal product were exempt
a priori from the paediatric investigation plan solely on the ground that it would permit only detection of rare signs in
the paediatric population, and, consequently, diagnosis of rare diseases in that population.
Thirdly, the applicant considers that the interpretation of Article 11(1)(b) of Regulation No 1901/2006 which it advocates
is the only one consistent with the general principles of freedom to conduct business, proportionality, legal certainty and
the rule of law.
With regard to the first two principles cited by the applicant, it should be noted that the right to pursue a trade or profession
freely is one of the general principles of European Union law (Case C‑280/93
Germany
v
Council
[1994] ECR I‑4973, paragraph 78, and Case T‑113/96
Dubois et Fils
v
Council and Commission
[1998] ECR II‑125, paragraph 74). It was moreover enshrined in Article 16 of the Charter of Fundamental Rights of the European
Union, proclaimed at Nice on 7 December 2000 (OJ 2000 C 364, p. 1), on which, since the entry into force of the Treaty of
Lisbon on 1 December 2009, the first subparagraph of Article 6(1) TEU has conferred the same legal value as the treaties. It
is settled case-law, however, that it may be restricted, provided that those restrictions correspond to objectives of general
interest pursued by the European Union and that they do not constitute a disproportionate and intolerable interference which
would affect the very substance of the right so guaranteed (see, to that effect,
Germany
v
Council
, paragraph 78; Case C‑183/95
Affish
[1997] ECR I‑4315, paragraph 42, and
Dubois et Fils
v
Council and Commission
, paragraph 74). The importance of the objectives pursued may justify restrictions which bring about even substantial negative
consequences for certain economic operators (see, to that effect, Case C‑331/88
Fedesa and Others
[1990] ECR I‑4023, paragraph 17, and
Affish
, paragraph 42).
Also, it is settled case-law that the principle of proportionality, which is one of the general principles of European Union
law, requires measures implemented by acts of the European Union to be appropriate for attaining the objective pursued and
not to go beyond what is necessary to achieve it (see Case C‑58/08
Vodafone and Others
[2010] ECR I‑4999, paragraph 51, and Joined Cases C-92/09 and C‑93/09
Volker und Markus Schecke and Eifert
[2010] ECR I‑0000, paragraph 74 and the case-law cited).
In the present case, the interpretation of Article 11(1)(b) of Regulation No 1901/2006 contained in the contested decision
limits the opportunity of obtaining a waiver of the obligation to submit a paediatric investigation plan and, in doing so,
ultimately constitutes a restriction of the right of pharmaceutical companies to conduct their business freely.
However, it must be held that the restriction of that right, which seeks to achieve a general-interest objective pursued by
Regulation No 1901/2006, namely, to improve medical care for the paediatric population, does not affect the actual substance
of that right, since the opportunities of obtaining a marketing authorisation are not, in fact, either totally removed or
even excessively reduced.
Moreover, as was stated in paragraph 63 above, the interpretation of Article 11(1)(b) of Regulation No 1901/2006 advocated
by the applicant is likely to make it easier to circumvent the obligation to submit a paediatric investigation plan. On the
other hand, the alternative interpretation of the provision at issue, adopted in the contested decision, is likely to ensure
achievement of the general-interest objective pursued by that regulation. In those circumstances, inasmuch as there is no
less restrictive alternative, it cannot be argued that the interpretation of the provision at issue adopted in the contested
decision is incompatible with the principle of proportionality.
That is all the more so since Article 20(1) of Regulation No 1901/2006 provides, under certain conditions, for the possibility
of deferring the initiation or completion of some or all of the measures contained in a paediatric investigation plan. Hence,
the requirement to submit data from paediatric studies conducted in the context of a paediatric investigation plan is not
likely to have the effect of blocking or delaying the authorisation of medicinal products for other populations (see recital
14 in the preamble to Regulation No 1901/2006).
Extension, as provided for in Article 36(1) of Regulation No 1901/2006, of the protection of the industrial property rights
in a medicinal product in respect of which a paediatric investigation plan has been produced also constitutes a suitable means
of mitigating the disadvantages for the company concerned resulting from the obligation to produce such a plan. That provision
states that where an application under Article 7 or 8 of Regulation No 1901/2006 includes the results of all studies conducted
in compliance with an agreed paediatric investigation plan, the holder of the patent or supplementary protection certificate
will be entitled to a six-month extension of the period referred to in Articles 13(1) and 13(2) of Council Regulation (EEC)
No 1768/92 of 18 June 1992 concerning the creation of a supplementary protection certificate for medicinal products (OJ 1992
L 182, p. 1).
Lastly, the provisions of Article 22 of Regulation No 1901/2006 also temper those disadvantages. They provide that if, following
the decision agreeing the paediatric investigation plan, the applicant encounters difficulties rendering the plan unworkable
or inappropriate, the applicant may propose changes to the Paediatric Committee or request a deferral or a waiver.
As regards the principles of legal certainty and the rule of law, also relied on by the applicant, the latter claims that
they require that pharmaceutical companies should know in advance what to expect when applying either for agreement for a
paediatric investigation plan or for a waiver pursuant to Article 11(1)(b) of Regulation No 1901/2006. The same principles
also mean that the EMA must follow a sufficiently precise set of rules when applying that article. If a ‘prior administrative
authorisation scheme’ such as that at issue is to be justified, it must, in any event, be based on objective, non-discriminatory
criteria known in advance to the undertakings concerned, in such a way as to circumscribe the exercise of the competent authorities’
discretion, so that it is not used arbitrarily.
It should be noted from the outset that the applicant’s reference, in the context of Article 11(1)(b) of Regulation No 1901/2006,
to ‘discretion’ is incorrect. The EMA adopts decisions under that provision in the exercise of circumscribed powers and not
as a matter of discretion. After taking into account the reasoned opinion of the Paediatric Committee, which, as stated in
paragraph 67 above, merely establishes the facts on the basis of scientifically-reasoned, objective evidence, the EMA is obliged
to grant the waiver sought if the relevant conditions are met. If not, it is obliged to refuse to grant it.
Therefore, if the interpretation contained in the contested decision is accepted, the principles of legal certainty and the
rule of law will not be affected in any way. In those circumstances, rejection of an application for waiver of the obligation
to submit a paediatric investigation plan will be based on objective, scientific evidence known to the person concerned. That
person will also be able to challenge that evidence effectively before the final decision is adopted, under the administrative
procedure laid down in Articles 13 and 25 of Regulation No 1901/2006.
It is apparent from all the above considerations that the interpretation of the contested provision given in the contested
decision is correct. The first plea must therefore be dismissed as unfounded.

The second plea: misuse of powers
By its second plea, the applicant claims that the EMA misused its powers since the true reason for refusing to grant the waiver
sought is the desire to compel the applicant to submit a paediatric investigation plan with a view to using Imagify for the
diagnosis of all types of myocardial perfusion defects in the paediatric population. That aim is clear, inter alia, from the
evolution of the opinions of the Paediatric Committee.
This plea cannot succeed.
According to settled case-law, the concept of misuse of powers refers to cases where an administrative authority has used
its powers for a purpose other than that for which they were conferred on it. A decision may amount to a misuse of powers
only if it appears, on the basis of objective, relevant and consistent evidence, to have been taken for purposes other than
those stated (see Joined Cases T‑155/03, T‑157/03 and T‑331/03
Cwik
v
Commission
[2005] ECR-SC I‑A‑411 and II‑1865 and the case-law cited). Therefore a misuse of powers can arise only when the authority
concerned enjoys wide discretion (see, to that effect, Case T‑489/93
Unifruit Hellas
v
Commission
[1994] ECR II‑1201, paragraph 84). However, misuse of powers is not possible in connection with the exercise of circumscribed
powers.
As was noted in paragraph 98 above, both the actions of the Paediatric Committee, which are confined to drawing up opinions
after establishing the facts on the basis of scientifically-reasoned, objective evidence, and the decisions taken by the EMA
in response to applications for waiver of the obligation to submit a paediatric investigation plan laid down in Article 11(1)(b)
of Regulation No 1901/2006 are indeed taken in the exercise of circumscribed powers. Thus, there can be no question of misuse
of powers in such cases.
Accordingly, the second plea must be rejected as unfounded, and the action must be dismissed in its entirety.

Costs
Under Article 87(2) of the Rules of Procedure, the unsuccessful party is to be ordered to pay the costs if they have been
applied for in the successful party’s pleadings. Since the applicant has been unsuccessful, it must be ordered to pay the
EMA’s costs, including those relating to the proceedings for interim measures, as sought by the EMA.
The first subparagraph of Article 87(4) of those Rules of Procedure provides that Member States and institutions which intervened
in the proceedings are to bear their own costs. Accordingly, the Portuguese Republic, the Kingdom of Belgium, the United Kingdom,
the French Republic and the Commission must bear their own costs, including those relating to the proceedings for interim
measures.
On those grounds,
THE GENERAL COURT (Third Chamber)
hereby:
1.
Dismisses the action;
2.
Orders Nycomed Danmark ApS to bear its own costs and those of the European Medicines Agency (EMA), including those relating
to the proceedings for interim measures;
3.
Orders the Portuguese Republic, the Kingdom of Belgium, the United Kingdom of Great Britain and Northern Ireland, the French
Republic and the European Commission to bear their own costs, including those relating to the proceedings for interim measures.
Czúcz
Labucka
Gratsias
Delivered in open court in Luxembourg on 14 December 2011.
[Signatures]
*
Language of the case: English.