62020TJ0223_RES
Case T‑223/20
Orion Oyj
v
European Commission
Judgment of the General Court (Tenth Chamber, Extended Composition) of 13 November 2024
(Medicinal products for human use – Generic medicinal products – Decision granting marketing authorisation for the medicinal product for human use Dexmedetomidine Accord – dexmedetomidine – Eligibility of a medicinal product as a reference medicinal product – Article 10(1) and (2) of Directive 2001/83/EC)
Approximation of laws – Medicinal products for human use – Marketing authorisation – Abridged procedure – Generic of a reference medicinal product – Exemption from the obligation to provide the results of pharmaceutical and pre-clinical tests or of clinical trials – Application for authorisation for a generic medicinal product – Possibility for an authority before which such an application is brought to request all relevant documentation from the authority which authorised the reference medicinal product – Examination of the eligibility of a medicinal product as a reference medicinal product – Competence of the Commission – Obligation to examine that eligibility – Condition – Information about the medicinal product capable of calling that eligibility into question
(Charter of Fundamental Rights of the European Union, Art. 41(1); European Parliament and Council Regulation No 726/2004, Art. 6(1); European Parliament and Council Directive 2001/83, Art. 10(1) and (2))
(see paragraphs 70-82)
Approximation of laws – Medicinal products for human use – Marketing authorisation – Abridged procedure – Generic of a reference medicinal product – Authority before which the application for authorisation for the generic medicinal product is brought which has already examined the clinical studies from the application for authorisation for the reference medicinal product – Clinical data enabling a well-founded and scientifically valid opinion to be formed on the benefit/risk balance of the reference medicinal product – Lack of additional clinical studies in the dossier relating to the reference medicinal product – Evidence calling into question the basis of the authorisation for the reference medicinal product on those data
(European Parliament and Council Regulation No 726/2014; European Parliament and Council Directive 2001/83)
(see paragraphs 101, 106-109)
Résumé
By its judgment, the General Court addresses the novel issue relating to the competence and obligation of the European Commission to examine, when analysing an application for marketing authorisation for a generic medicinal product, the eligibility as a reference medicinal product of the medicinal product for which the marketing authorisation was granted by a national authority, where information provided to the Commission by the holder of the latter medicinal product may call into question its eligibility as a reference medicinal product.
Orion Oyj is a pharmaceutical company which developed the active substance called ‘dexmedetomidine hydrochloride’. In 1994, it granted Abbott Laboratories Inc. (‘Abbott’) an exclusive licence to manufacture and market dexmedetomidine hydrochloride in ‘all countries and territories of the world except Finland, Sweden, Norway, Denmark and Iceland’. In 1998, Abbott submitted to the European Medicines Agency (EMA) (
1
) an application for marketing authorisation for that substance, under the trade name Precedex. However, the EMA’s Committee for Medicinal Products for Human Use (‘the CHMP’) (
2
) raised serious concerns about the adequacy of certain clinical studies submitted by Abbott. The latter therefore withdrew that application on account of the cost of the additional clinical studies required by the CHMP and requested various marketing authorisations from several European countries, including the Czech Republic. According to Orion, the clinical data submitted in support of the application for marketing authorisation to the Státní ústav pro kontrolu léčiv (SUKL, State Institute for Drug Control, Czech Republic) were identical to the data enclosed with the application made to the EMA, since Abbott had not carried out any additional study. Subsequently, on 23 October 2002, Abbott obtained a marketing authorisation from the SUKL for Precedex.
In 2002, Abbott returned to the applicant part of its exclusive licence, namely the part relating to the manufacture and marketing of Precedex in States which, on that date, were Members of the European Union.
In 2004, following the Czech Republic’s accession to the European Union, Abbott assigned the remainder of the exclusive licence to Hospira Inc., which, in 2008, returned it to Orion. The latter then requested the withdrawal of the Czech marketing authorisation for Precedex, which became effective as from 30 July 2010.
In 2005, Orion also applied for marketing authorisation for a medicinal product called Dexdor of which the active substance was dexmedetomidine hydrochloride. That marketing authorisation was granted by the Commission in 2011.
In 2018, Accord Healthcare submitted to the EMA an application for marketing authorisation for Dexmedetomidine Accord – dexmedetomidine, a generic medicinal product of the reference medicinal products Precedex, for which the marketing authorisation had been granted by the SUKL in 2002, and Dexdor, for which the marketing authorisation had been granted by the Commission in 2011. (
3
) After the Commission granted the marketing authorisation for that generic medicinal product in 2020, Orion sought its annulment. (
4
)
Findings of the Court
The Court rules, in the first place, on the Commission’s competence to examine the eligibility of Precedex as a reference medicinal product and its obligation in that regard. It recalls that no medicinal product may be placed on the market unless a marketing authorisation has been granted by the competent authority (
5
) and that an abridged procedure has been provided for with a view to granting authorisation for a generic medicinal product of a reference medicinal product. (
6
) That procedure exempts the party applying for marketing authorisation for the generic medicinal product from the obligation to provide the results of pharmaceutical and pre-clinical tests or of clinical trials with the aim of saving the time and expense needed to gather that data and to avoid the repetition of tests on humans or animals where not absolutely necessary. However, the abridged procedure does not provide for any relaxation of the requirements of safety and efficacy which must be met by medicinal products approved in the European Union. Accordingly, that procedure is only available where all the particulars and documents demonstrating the safety and efficacy of the reference medicinal product are and remain available to the competent authority before which the application for marketing authorisation for a generic medicinal product is brought.
Furthermore, the Commission and the competent authorities of the Member States, which are subject to the same harmonised rules, may consider that a marketing authorisation granted by one of them was preceded by a careful examination of the results of pharmaceutical and pre-clinical tests and of clinical trials, thus ensuring a reliable assessment of the benefit/risk balance of the medicinal product, in accordance with the substantive requirements stemming from EU law. Therefore, the Commission was able, in principle, to rely on the confirmation which it had requested from the SUKL that the Czech marketing authorisation for Precedex had indeed been granted.
However, the authority before which an application for marketing authorisation for a generic medicinal product is brought – the Commission in the present case – may request that the authority which authorised the reference medicinal product transmit to it not only a confirmation that the reference medicinal product is or has been authorised, but also all other relevant documentation. The Commission may therefore request more information from the competent authority which authorised the marketing authorisation for the reference medicinal product, and even request that that authority give it access to the dossier relating to that marketing authorisation, where it possesses evidence which calls into question the fact that that marketing authorisation is based on a dossier demonstrating the safety and efficacy of that medicinal product.
Accordingly, the Court concludes, both on the basis of Article 10(1) and (2) of Directive 2001/83, (
7
) and of the principle of sound administration, laid down in Article 41(1) of the Charter of Fundamental Rights of the European Union, that the Commission was competent to examine the eligibility of Precedex as a reference medicinal product and was required to do so where the information provided by the holder of the reference medicinal product before the decision granting marketing authorisation for the generic medicinal product was adopted may have called into question the eligibility of that product as a reference medicinal product.
In the second place, the Court addresses the evidence calling into question the eligibility of Precedex as a reference medicinal product. In that regard, it notes that, while it is common practice that the authority before which the application for marketing authorisation for the reference medicinal product is brought is the first to assess the clinical studies and the competent authority before which the application for marketing authorisation for the generic medicinal product is brought then reproduces that assessment, in the present case, the order of events is reversed. In particular, the CHMP, tasked in 2018 with examining the application for marketing authorisation for the generic medicinal product, Dexmedetomidine Accord, had already, in 2001, examined the clinical studies relating to the application for marketing authorisation for the reference medicinal product, Precedex, and raised serious concerns about them, before they were submitted to the SUKL.
Accordingly, the possible lack of additional clinical studies in the dossier relating to the Czech marketing authorisation for Precedex was evidence which the Commission possessed and which called into question the fact that that marketing authorisation was based on clinical data enabling a well-founded and scientifically valid opinion to be formed on the benefit/risk balance of that medicinal product. (
8
)
(
1
)	That agency, at the time of the facts, was called the European Agency for the Evaluation of Medicinal Products (EMEA).
(
2
)	That committee, at the time of the facts, was called the Committee for Proprietary Medicinal Products (CPMP).
(
3
)	The application was submitted under Article 10(2) 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).
(
4
)	Annulment 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).
(
5
)	Article 3(1) of Regulation No 726/2004, and Article 6(1) of the same regulation and Article 6(1) of Directive 2001/83.
(
6
)	Article 10 of Directive 2001/83.
(
7
)	Directive 2001/83 is applied to the centralised procedure on the basis of Article 6(1) of Regulation No 726/2004.
(
8
)	Article 8(3) of Directive 2001/83, read in conjunction with Annex I to that directive.