On 16 March 2023, in Joined Cases C‑438/21P to C‑440/21P, the Court of Justice of the European Union (CJEU) interpreted the concept of a ‘global marketing authorisation’. It held that Article 6(1) of Directive 2001/83 (the Community Code) sets out exhaustively the line extensions for which the marketing authorisations (MAs) will fall under the same global MA as the initial MA. Consequently, medicinal products that solely differ as to their therapeutic moiety or active substances may not be considered as line extensions caught by Article 6(1), and thus enjoy their own regulatory data protection (RDP) period. As a result, the CJEU set aside the General Court’s broad and generic-friendly interpretation (in case T‑611/18).

Regulatory data protection and global MAs

A key incentive for innovation in pharmaceutical law is the RDP period. Firstly, during a data exclusivity period of eight years, other pharmaceutical companies may not apply for an MA by relying on the results of pre-clinical tests and clinical trials of the originator’s reference product. Secondly, during a subsequent market protection period of two years, medicinal products that have been authorised by reference to such results may still not be marketed.

The concept of a global MA (Article 6(1) of the Community Code) affects whether a new medicinal product can benefit from its own RDP. The global MA will not only capture the initial MA for the first medicinal product, but also any additional strengths, pharmaceutical forms, administration routes, presentations, as well as any related variations and extensions. These so-called “line extensions” will therefore not benefit from their own RDP.

It is worth noting that the European Commission has recently proposed a new RDP framework as part of its pharma package, and that the proposal does not currently change the concept of a global MA.

Factual background and the General Court’s ruling

At the origin of the CJEU’s decision lies Tecfidera®, which contains the active substance dimethyl fumarate (DMF) for the treatment of multiple sclerosis (MS). In January2014, Biogen was granted a central MA for Tecfidera®. DMF is also part of Biogen’s fixed combination product Fumaderm®, which consists of DMF and monomethyl fumarate (MEF) salts, is indicated for treating psoriasis. Fumaderm® was granted an MA in Germany in 1994. The Commission’s decision incorporated the assessment of the EMA’s Committee for Medicinal Products for Human Use (CHMP) that Tecfidera® and Fumaderm® did not belong to the same global MA because of their different qualitative composition in terms of active substances, and therefore benefitted from their own RDP period.

In 2017, Polpharma applied for an MA for its generic version of Tecfidera®, claiming that Tecfidera® fell within the same global MA as Fumaderm® as a result of which Tecfidera’s RDP period had already expired. The EMA unsurprisingly denied Polpharma’s application on the basis that Tecfidera’s RDP period had not yet expired. Polpharma brought an annulment action before the General Court, and argued that MEF in Fumaderm® did not contribute to its therapeutic effect.

The General Court first addressed procedural issues relating to Article 277 of the Treaty on the Functioning of the EU (TFEU). This provision contains the ‘objection of illegality’ that permits a party to challenge, as an incidental plea, and in order to obtain the annulment of a decision of direct and individual concern to that party, the validity of an earlier EU act of general application forming the legal basis of the contested decision. The General Court decided that a Commission implementing decision granting an MA is an act of general application, and that Polpharma was entitled to challenge the CHMP’s scientific opinion as it was incorporated in the Commission’s implementing decision.

On the merits, the General Court largely followed Polpharma’s reasoning. It considered that both the CHMP and the Commission had failed to assess the clinical role of MEF in Fumaderm®. Left without a valid legal basis, the EMA’s refusal was thus annulled, forcing the EMA to re-assess MEF’s clinical role.

Biogen, the EMA and the European Commission appealed the General Court’s ruling to the CJEU. Pending the appeal and without prejudice to its position in those proceedings, the EMA implemented the General Court’s ruling by conducting an ad hoc assessment relating to the therapeutic effect of MEF within Fumaderm®. The CHMP could not establish such a clinically relevant therapeutic contribution. In line with the General Court’s decision, Tecfidera® could therefore not benefit from an independent RDP, as a result of which Polpharma’s MA was granted on 13 May 2022.

The successful appeal before the Court of Justice

In a relatively short judgment, the CJEU first confirmed the General Court’s ruling on the procedural issue. Polpharma could indeed bring an action for the annulment of the European Commission’s decision because Polpharma did not have a current and vested interest in bringing proceedings against that decision during the prescribed period.

On the merits, however, the CJEU overruled the General Court. The CJEU held that Article 6(1) of the Community Code sets out exhaustively the line extensions that are caught by the same global MA as the initial MA. Medicinal products that differ as to their therapeutic moiety or active substances, such as Tecfidera® (a mono-substance) and Fumaderm® (a combination product), are not caught by Article6(1) and thus have their own RDP period. Whether MEF exerts a clinically relevant therapeutic contribution within Fumaderm® is irrelevant, and it is sufficient for the EMA to conclude that the two drugs differ in their qualitative compositions to exclude them from the same global MA.

Aftermath and final remarks

The ruling comes at a crucial time for Biogen. Since the introduction of generic versions following the General Court’s ruling, annual sales of Tecfidera® have significantly dropped. Meanwhile, on 2May2023, the Commission granted Tecfidera® an additional year of market protection to 2February2025, and, as we understand, in mid-May 2023, new annulment actions have already been launched against this decision before the General Court. On the other side of the spectrum, various generic versions continue to benefit from an MA, and in Belgium, Mylan’s generic version still seems to be available on the market. At present, Biogen continues fighting the generic MAs at the EU-level before the General Court and will undoubtedly also enforce its rights before the national courts.

If you would like any further information, please contact Kirian Claeyé ([email protected]) or Bart Junior Bollen ([email protected]).