62019TJ0549_RES
Case T‑549/19
Medac Gesellschaft für klinische Spezialpräparate mbH
v
European Commission
Judgment of the General Court (Tenth Chamber), 23 September 2020
(Medicinal products for human use – Orphan medicinal products – Application for marketing authorisation for the medicinal product Trecondi-treosulfan – Decision to remove a medicinal product from the Register of Orphan Medicinal Products – Article 3(1)(b) of Regulation (EC) No 141/2000 – Concept of ‘satisfactory method’ – Article 5(12)(b) of Regulation No 141/2000 – Error of law)
Approximation of laws – Uniform legislation – Medicinal products for human use – Orphan medicinal products – Review procedure for designating a medicinal product as an orphan medicinal product – Satisfactory method of diagnosis, prevention or treatment of the same condition that has been authorised in the European Union – Concept of ‘authorisation’ – Use of a medicinal product otherwise than in accordance with the summary of product characteristics (SmPC) – Not included
(European Parliament and Council Regulation No 141/2000, Art. 3(1)(b); Commission Regulation No 847/2000, Art. 2(3), second subparagraph, heading (a); European Parliament and Council Directive 2001/83, Arts 6(1), first and second subparagraphs, 8(3)(j), 11, 21(1) and 23(3))
(see paragraphs 49, 52-60)
Approximation of laws – Uniform legislation – Medicinal products for human use – Orphan medicinal products – Review procedure for designating a medicinal product as an orphan medicinal product – Satisfactory method of diagnosis, prevention or treatment of the same condition that has been authorised in the European Union – Concept of ‘same condition’ – Criteria for assessment – Taking into account of all the essential elements surrounding authorised use of the existing method defined in the summary of product characteristics (SmPC) – Extension of that authorisation to the diagnosis, prevention or treatment of conditions or categories of patients not mentioned in the SmPC – Not included
(European Parliament and Council Regulation No 141/2000, Art. 3(1)(b); European Parliament and Council Regulation No 726/2004, recital 14; European Parliament and Council Directive 2001/83, recital 7, Arts 6(1), second subparagraph, 23(3) and 26)
(see paragraphs 61-65)
Approximation of laws – Uniform legislation – Medicinal products for human use – Orphan medicinal products – Review procedure for designating a medicinal product as an orphan medicinal product – Satisfactory method of diagnosis, prevention or treatment of the same condition that has been authorised in the European Union – Reference medicinal products partially authorised for the conditions and the populations covered by the medicinal product which forms the subject of the application – Not included
(European Parliament and Council Regulation No 141/2000, recital 1, Arts 3(1)(b) and 7(3); European Parliament and Council Regulation No 1901/2006, recital 4)
(see paragraphs 66-81)
Résumé
By decision of the Commission of 23 February 2004, a potential treosulfan-based medicinal product, sponsored by the applicant, Medac Gesellschaft für klinische Spezialpräparate mbH, was designated as an orphan medicinal product and entered into the European Union Register of Orphan Medicinal Products in accordance with Regulation No 141/2000. (
1
)
On 13 October 2017, the applicant submitted to the European Medicines Agency (EMA) and, more specifically, to the Committee for Orphan Medicinal Products provided for in Regulation No 141/2000, a report on the maintenance of the designation of treosulfan as an orphan medicinal product at the time when the marketing authorisation (MA) was granted. Following the investigation procedure, on 20 June 2019, the Commission adopted a decision granting an MA for the treosulfan-based medicinal product under the commercial name Trecondi-treosulfan; (
2
) however, it decided that it no longer met the criteria for designation established in Article 3 of Regulation No 141/2000 and that, therefore, it could not be designated as an orphan medicinal product. Article 3(1)(b) of Regulation No 141/2000 provides for alternative criteria for the designation of a medicinal product as an orphan medicinal product, namely that there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorised in the European Union (first alternative), or, if such a method exists, that the medicinal product in question will be of significant benefit, compared with existing satisfactory methods, to those affected by that condition (second alternative). In that context, after the final opinion of the Committee for Orphan Medicinal Products, the Commission found that, as regards the existence of a significant benefit, the applicant had established that Trecondi-treosulfan provided a significant benefit in comparison with the medicinal products busulfan (Busilvex) and thiotepa (Tepadina) but not in comparison with melphalan- and cyclophosphamide-based medicinal products. Consequently, the medicinal product Trecondi-treosulfan was removed from the European Union Register of Orphan Medicinal Products.
By its judgment of 23 September 2020, the Court, before which the applicant had brought proceedings to have the contested decision annulled, upheld the first two pleas relied on and, accordingly, annulled that decision in part in so far as it provided that the medicinal product Trecondi-treosulfan was no longer to be classified as an orphan medicinal product.
First of all, the Court stated that Regulation No 141/2000 provides as the first of the two alternative criteria for the designation of a medicinal product as an orphan medicinal product that there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorised in the European Union. According to that criterion, in order for a medicinal product to be eligible for classification as a ‘satisfactory method’ it must be ‘authorised’ in the European Union or in a Member State of the European Union for the same orphan ‘condition’ as that covered by the medicinal product for which an MA as an orphan medicinal product is sought. For the purposes of determining the scope of authorisation of a medicinal product in the European Union, the Court observed that, pursuant to Directive 2001/83, (
3
) no medicinal product may be placed on the market of a Member State unless an MA has been issued by the competent authorities of that Member State. (
4
) Next, with a view to the grant of an MA at national level, an application must be made to the competent authority and must include a summary of product characteristics (SmPC), (
5
) containing a set of information on the medicinal product in question in a specified order. The SmPC is approved by that authority at the time when the MA is granted and it forms part of the decision granting the MA, which defines the scope of the authorisation of the existing medicinal product. After an MA has been granted, Directive 2001/83 requires the MA holder to ensure that the product information is kept up to date with, in particular, the current scientific knowledge.
It follows, according to the Court, first, that the off-label use of a medicinal product cannot be regarded as being ‘authorised’ and, consequently, cannot constitute a ‘satisfactory method’ within the meaning of Regulation No 141/2000.
Second, the Court stated that, in order to determine whether the existing method referred to covers the same ‘condition’ as that covered by the orphan medicinal product which forms the subject of the application, account must be taken of all the essential elements surrounding authorised use of the existing method, and in particular its therapeutic indication and its target population, as defined in its SmPC, which cannot but be interpreted strictly. Thus, any variation to the SmPC must be further assessed in relation to the benefit/risk balance and the quality, safety and efficacy of the medicinal product for a proposed new indication must be subject, as appropriate, to clinical tests. Consequently, the MA for a medicinal product does not extend to the diagnosis, prevention or treatment of conditions or categories of patients that are not mentioned in its SmPC.
Third, the Court states that, where the medicinal product which is the subject of an application for an MA as an orphan medicinal product is intended for the diagnosis, prevention or treatment of conditions or categories of patients for which, at least in part, the reference medicinal products are not authorised, according to their respective SmPCs, those latter medicinal products cannot be regarded as being ‘satisfactory methods’ for those conditions or for those categories. Regard being had to the purpose of Regulation No 141/2000, which is to provide incentives for the research, development and placing on the market of medicinal products intended to treat rare conditions, the exclusion of a potential medicinal product from the benefits provided for by that regulation on the ground that ‘satisfactory methods’ exist only for a portion of the rare conditions covered by it is contrary to the intended purpose.
In addition, the Court emphasised that Regulation No 141/2000 allows, specifically when an MA is granted for an orphan medicinal product, account to be taken of cases of partial overlap with MAs for other medicinal products. (
6
) Thus, in so far as certain therapeutic indications for a medicinal product fulfil the criteria for designation set out in Article 3 of that regulation, that medicinal product is, in principle, eligible to be designated as an orphan medicinal product for those indications, whereas, as regards the indications in respect of which it does not fulfil the criteria set out in Article 3 of that regulation, a separate MA may be granted, outside the scope of that regulation.
After having examined whether, in the present case, the treatment of the orphan condition and the categories of patients targeted by Trecondi-treosulfan are also covered by melphalan- and cyclophosphamide-based medicinal products, according to their respective SmPCs, the Court found that the SmPCs of the medicinal products which are being compared show clear differences. It is clear from the description of the SmPC of Trecondi-treosulfan that the latter covers pathological conditions and populations which are not covered by the SmPCs of melphalan- and cyclophosphamide-based medicinal products. It follows that, for those pathological conditions and populations, melphalan- and cyclophosphamide-based medicinal products cannot be regarded as satisfactory methods within the meaning of the first alternative in Article 3(1)(b) of Regulation No 141/2000.
(
1
)	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).
(
2
)	European Commission Implementing Decision C(2019) 4858 final of 20 June 2019 granting marketing authorisation for the medicinal product for human use ‘Trecondi-treosulfan’ under Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Union 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).
(
3
)	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).
(
4
)	In accordance with the first subparagraph of Article 6(1) of Directive 2001/83.
(
5
)	In accordance with Article 8(3)(j) of Directive 2001/83.
(
6
)	In accordance with Article 7(3) of Regulation No 141/2000.