Three recent judgments handed down by the Central Administrative Courts Nos. 4, 10 and 2 on 30 March, 14 May 2021 and 27 May 2021 (ordinary proceedings Nos. 26/2019, 27/2019 and 26/2019), respectively, shed light on the data exclusivity and, in particular, on the consequences of the use and re-use of data from clinical trials or pre-clinical studies within the framework of a marketing authorisation dossier for a medicinal product (hereinafter, “MA”).
These judgments establish that the use of data from clinical trials or pre-clinical studies within the framework of a marketing authorisation dossier for a medicinal product (hereinafter “MA”) exhausts its data exclusivity protection, regardless of whether they are submitted in the application or for a subsequent variation, such as a new dosage, pharmaceutical form, route of administration and additional presentations, as well as any other modifications and extensions to the authorisation dossier that may be introduced, not enjoying additional periods of protection if the same data are used in other MA dossiers.
This was the case for clinical trial data submitted, first in the context of the marketing authorisation for the medicinal product Avidart® (active substance dutasteride) and, then, in the application for the MA of the medicinal product Duodart® (combination of the active substances dutasteride and tamsulosin).
The first MA in the European Union for Avidart® was granted in July 2002. Under the regime in force at that time in Spain, its data exclusivity period was 6 years, which expired in July 2008.
Duodart® was first approved in the European Union on 16 April 2016.
The conflicting data are data from a clinical study on the simultaneous use of dutasteride and tamsulosin entitled 2-year CombAT Study. In 2008, the owner of the MA on Avidart® -which is the plaintiff in the analysed judgments (hereinafter, the “Plaintiff”)-applied for a variation to introduce an indication for combination therapy consisting of the simultaneous use of dutasteride (0.5 mg) with tamsulosin (0.4 mg) in that MA. This variation was approved and included in its summary of product characteristics as a new indication for combination therapy in April 2008. The Plaintiff used the same 2-year CombAT Study to apply for the registration of Duodart®.
Several years after the end of the data exclusivity period for Avidart®, specifically in 2016, a different laboratory -which is a co-defendant in the analysed judgments (hereinafter, the “Co-defendant”)- applied to the Spanish Agency for Medicines and Health Products (hereinafter, “AEMPS”) for several MAs for a dutasteride/tamsulosin combination created by the group of companies to which it belongs. The MA applications for these combinations were submitted as a complete dossier – either general or for a fixed-dose combination – in the modality of mixed dossier, in accordance with Article 6 of Royal Decree 1345/2007 and Article 8.3 of Directive 2001/83, and in no case was it submitted as a generic of Duodart®. The mixed dossier modality allows the applicant to replace part of the non-clinical and clinical reports to be provided in the full dossier by bibliographic references. Among the numerous literature references submitted in that dossier was the 2-year CombAT Study.
The Plaintiff considered that the use of the 2-year CombAT Study in the documentation used to apply for Co-defendant’s dutasteride/tamsulosin combination constituted a breach of the data exclusivity period for Duodart®, despite the fact that this study had already been used to introduce the indication for combination therapy of Avidart® (dutasteride) with tamsulosin in the summary of product characteristics of Avidart®.
The Plaintiff appealed against the decisions granting the MAs requested by the Co-Defendant for the combination of dutasteride/tamsulosin. The AEMPS dismissed the appeals filed by the Plaintiff for lack of standing. The Plaintiff filed a contentious-administrative appeal against these decisions.
To date, six judgments have been issued by central administrative courts dismissing the appeals filed by the Plaintiff.
Except for one case (Judgment of 14 May 2021 of Court No. 10, PO 27/2010), all the judgments handed down consider that the Plaintiff lacks standing to bring an administrative appeal.
The merits of the case have been assessed only in three of the six cases. These are the final judgments handed down by the Central Administrative Courts Nos. 4, 10 and 2 on 30 March, 14 May 2021 and 27 May 2021 (ordinary proceedings Nos. 26/2019, 27/2019 and 26/2019), respectively, which dismissed the Plaintiff’s appeal, considering that it was fully permissible for the Co-defendant to submit the 2-year CombAT Study among the documentation in the dossier of its dutasteride/tamsulosin combinations. The three judgments reached the conclusion that the 2-year CombAT Study benefited from the Avidart® data exclusivity period, without it being appropriate to apply a new exclusivity period to the cited study as a consequence of having been resubmitted in the Duodart® dossier.
The Central Administrative Court No. 4 is very clear in stating the following in its Judgment of 30 March 2021:
The period of data protection refers to the registration file as a whole from the moment it is authorised, and not to the data that are part of the file individually from the moment they are included in the file.
The Central Administrative Court No. 2, in its Judgment of 27 May 2021, refers to the previous judgment, and states that “for reasons of coherence and consistency, we will maintain the same criterion“.
The Central Administrative Court No. 10, in its judgment of 14 May 2021, makes a detailed analysis of the issue and bases its decision mainly on the concept of global authorisation and the case law of the Court of Justice of the European Union on this concept and data exclusivity.
We recall that the concept of “global authorisation” refers to the fact that the marketing authorisation includes the following: any additional dosage, pharmaceutical form, route of administration and presentation, as well as any amendments and extensions made to a MA, and that both Article 9.2 of RD-Law 1/2015 and Article 4.2 of RD 1345/2007 indicate that all amendments belonging to the same global authorisation are considered made to the same MA for the purposes of the application of the data exclusivity periods, even when they are made through separate MAs.
The Court quotes the Judgment of the CJEU of 28 June 2017 Novartis Europharma v. European Commission, Teva Pharma BV and Hospira UK Ltd (C-630/2015). This judgment dealt precisely with a case in which the innovator laboratory had obtained a marketing authorisation for new indications -modifying the dosage to adapt to the new indications – for a medicinal product for which it already had a marketing authorisation, in which the laboratory could have included the new indication instead of applying for a new marketing authorisation. The CJEU established that as it was a variation that could have been introduced in the initial MA, the information contained therein was protected by the period of data exclusivity of the initial marketing authorisation without being able to enjoy an additional period for having applied for the new indications with the corresponding change in dosage through a new MA.
In addition, the Central Court no. 10 highlights that the applicant not only included the four studies corresponding to CombAT2, but thirteen other studies that were also taken into account by the Administration, so that in no case has the possible relevance of these studies in the granting of the MA been accredited, drawing particular attention to the fact that two other articles of the thirteen taken into consideration by the AEMPS also contained references to the concomitant use of dutasteride and tamsulosin in the same proportions as those contained in the D/T medicinal product (…), so that the applicant’s insistence on focusing on the use of the CombAT2 study is inconsistent.
These are the first judgments in Spain referring to this issue, where it is made clear that the use of data from clinical trials or pre-clinical studies in a MA in its entirety as a global authorisation exhausts its possible right to data exclusivity ex art. 18 of RD-Law 1/2015.
 First Transitional Provision of Royal Legislative Decree 1/2015, of 24 July, approving the revised text of the Law on guarantees and rational use of medicines and health products (hereinafter RD-L 1/2015) in relation to Article 11.3 of Royal Decree 767/1993, of 21 May, regulating the evaluation, authorisation, registration and conditions of dispensing of pharmaceutical specialities and other industrially manufactured medicines for human use.
 Royal Decree 1345/2007 of 11 October 2007 regulating the procedure for the authorisation, registration and conditions of dispensing of industrially manufactured medicinal products for human use.
 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.
 “Where a medicinal product has been granted authorisation in accordance with the preceding paragraph, any additional strengths, pharmaceutical forms, routes of administration and presentations, as well as any other variations and extensions to the authorisation dossier, shall be subject to authorisation or notification as provided for in the regulations governing the procedure for the authorisation, registration and conditions of supply of industrially manufactured medicinal products for human use. All such variations shall be considered as belonging to the same global marketing authorisation, in particular for the purposes of the application of data exclusivity periods”.
 Where a medicinal product has been granted an initial marketing authorisation, any additional strengths, pharmaceutical forms, routes of administration and presentations, as well as any variations and extensions, shall also be granted an authorisation. All such marketing authorisations shall be considered as belonging to the same global marketing authorisation, in particular for the purposes of the application of data exclusivity periods, as well as for subsequent variations to the authorisation affecting a whole range of medicinal products from the same marketing authorisation holder containing the same active substance.