Orders nº T-52/09 of Court of First Instance of the European Communities, April 24, 2009

• Resolution Date: April 24, 2009
• Issuing Organization: Court of First Instance of the European Communities
• Decision Number: T-52/09

(Application for interim measures – Marketing authorisation for a medicinal product – Ultrasound echocardiographic imaging agent for diagnostic purposes (perflubutane) – Refusal by the EMEA to grant a waiver from the obligation to submit a paediatric investigation plan – Application for suspension of operation of a measure and interim measures – No urgency)

In Case T‑52/09 R,

Nycomed Danmark ApS, established in Roskilde (Denmark), represented by C. Schoonderbeek and H. Speyart van Woerden, lawyers,

applicant,

v

European Medicines Agency (EMEA), represented by V. Salvatore and N. Rampal Olmedo, acting as Agents,

defendant,

APPLICATION, first, for suspension of the operation of the EMEA’s decision of 28 November 2008 rejecting the application for a product-specific waiver concerning perflubutane and, secondly, for the grant of interim measures,

THE PRESIDENT OF THE COURT OF FIRST INSTANCE OF THE EUROPEAN COMMUNITIES

makes the following

Order

1 The applicant, Nycomed Danmark ApS, is a Danish manufacturer and supplier of medicines and pharmaceutical products. It is part of the Nycomed group of companies, which operates worldwide out of headquarters in Switzerland. According to its website, the Nycomed group of companies achieved total sales of EUR 3.3 billion in 2008.

2 The applicant developed an ultrasound echocardiographic imaging agent to be marketed under the brand name Imagify (‘Imagify’), which it states is intended to detect coronary artery disease (‘CAD’), that is, chronic disease characterised by obstruction of the coronary arteries, in patients suffering from chest pain and in whom inducible ischemia, that is reduced blood flow to an organ caused by stress or increased physical activity, is suspected.

3 The applicant intends to apply to the Commission for a Community marketing authorisation (‘CMA’) for Imagify.

4 The present dispute concerns the procedure for validation of that CMA application, which takes place before the European Medicines Agency (EMEA) prior to the actual authorisation procedure.

Legal framework

5 Under Articles 1 and 6 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, no medicinal product, including any product intended for diagnostic purposes such as Imagify, 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 the provisions thereof, or the Commission has granted a CMA in accordance with Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (OJ 2004 L 136, p. 1), in conjunction with 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 2004 L 378, p. 1).

6 Regulation No 726/2004 provides for a two-stage procedure for granting CMAs: in the first stage of the procedure, which is governed by Articles 5 to 9 of Regulation No 726/2004, the EMEA’s Committee for Medicinal Products for Human Use draws up an opinion on the CMA application; in the second stage of the procedure, which is governed by Article 10 of Regulation No 726/2004, the Commission takes a decision granting or refusing the CMA.

7 Article 6 of Regulation No 726/2004 refers, with respect to the content of a CMA application, to the particulars and documents as referred to in, inter alia, Article 8(3) of Directive 2001/83. It thus follows from a joint application of Article 6 of Regulation No 726/2004 and Article 8(3)(e) of Directive 2001/83 that a CMA application must include the therapeutic indication – an expression which should be taken to include diagnostic indications – for which the CMA is being sought for the medicinal product concerned.

8 A combined reading of Article 1(28a) and Article 26 of Directive 2001/83, and also Article 12 of Regulation No 726/2004, read in the light of recital 14 in the preamble to that regulation, shows that the CMA is refused if, after verification of the relevant particulars and documents, it emerges, inter alia, that the risk-benefit balance of the medicinal product in question is not considered to be favourable. In that regard, the positive therapeutic or diagnostic effects of the medicinal product in question in relation to the risks related to its use, that is, any risk for the health of the patient or for public health relating to the quality, safety or efficacy of the medicinal product and any risk of undesirable effects on the environment, are to be evaluated (Article 1(28) of Directive 2001/83).

9 Regulation No 1901/2006, which is also relevant for the granting of CMAs (see paragraph 5 above), aims to facilitate the development and accessibility of medicinal products for paediatric use, to ensure that those medicinal products are subject to ethical research of high quality and are appropriately authorised for paediatric use, and to improve the information available on the use of medicinal products in the various paediatric populations (recital 4 in the preamble to Regulation No 1901/2006).

10 Under Article 7 of Regulation No 1901/2006, a CMA application can be validated only if it includes, in addition to the particulars and documents referred to in Article 8(3) of Directive 2001/83, the results of the studies performed in compliance with a paediatric investigation plan (‘PIP’) previously agreed by the EMEA, a decision of the EMEA granting a waiver from the obligation to submit a PIP, or a decision of the EMEA granting a deferral for implementation of the PIP.

11 Under Article 11(1) of Regulation No 1901/2006, a waiver is granted if there is evidence, inter alia, that the medicinal product in question is likely to be ineffective or unsafe in the paediatric population (Article 11(1)(a) of Regulation No 1901/2006) or that ‘the disease or condition for which the specific medicinal product … is intended occurs only in adult populations’ (Article 11(1)(b) of Regulation No 1901/2006).

12 Articles 13 and 25 of Regulation No 1901/2006 lay down the applicable procedure for the adoption of a decision on an application for a waiver. Thus, once the Paediatric Committee established within the EMEA adopts an opinion as to whether or not a product-specific waiver should be granted, the EMEA transmits that opinion to the applicant, who may submit to the EMEA a request for a re-examination of the opinion. Following receipt of such a request for re-examination, the Paediatric Committee issues a new opinion confirming or revising its previous opinion. The new opinion, which is definitive, must be duly reasoned and a statement of reasons for the conclusion reached must be annexed thereto. Following receipt of the definitive opinion of the Paediatric Committee, the EMEA adopts a decision, which is communicated to the applicant in writing and must annex the definitive opinion of the Paediatric Committee.

13 If a waiver is not obtained, the applicant concerned may either terminate the application procedure for obtaining a CMA or submit a draft PIP for agreement by the EMEA and, where applicable, request a deferral. Under Article 15(2) of Regulation No 1901/2006, the PIP must, inter alia, 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.

14 Articles 20 and 21 of Regulation No 1901/2006 provide as follows with respect to deferrals:

‘Article 20

1. At the same time as the [PIP] is submitted …, a request may be made for deferral of the initiation or completion of some or all of the measures set out in that [PIP]. Such deferral shall be justified on scientific and technical grounds or on grounds related to public health.

   In any event, a deferral shall be granted when it is appropriate to conduct studies in adults prior to initiating studies in the paediatric population or when studies in the paediatric population will take longer to conduct than studies in adults.

   …

   Article 21

1. At the same time as the Paediatric Committee adopts a positive opinion [on the PIP submitted], it shall, … following a request submitted by the applicant under Article 20, adopt an opinion, if the conditions specified in Article 20 are met, in favour of deferring the initiation or completion of some or all of the measures in the [PIP].

   An opinion in favour of a deferral shall specify the time-limits for initiating or completing the measures concerned.

2. As soon as the Paediatric Committee adopts an opinion in favour of deferral, as referred to in paragraph 1, the procedure laid down in Article 25 shall apply.’

   Background to the dispute

   15 Myocardial perfusion defects are a sign of inducible ischemia in the heart muscle, and they may therefore be caused by CAD. It is also possible, however, that those perfusion defects are caused by other diseases, such as congenital heart defects, coronary anomalies or cardiomyopathies.

   16 The applicant has focused on the clinical development of Imagify for use in diagnosing adults who suffer from chest pain which might be caused by inducible myocardial ischemia as an early sign of CAD. The CMA application for Imagify which the applicant intends to submit will therefore be for the following therapeutic indication: ‘[d]iagnosing coronary artery disease in patients with chest pain being evaluated for inducible ischemia’.

   17 Pre-clinical and clinical studies and tests were performed by the applicant on the specific group of adult patients suffering from chest pains in order to fulfil the requirements...