On 6 October 2022, Advocate General Medina issued an Opinion in three joined appeal cases brought by the European Commission, the EMA and Biogen against Pharmaceutical Works Polpharma. The opinion touches on the concept of global marketing authorization (GMA), and on the principle of mutual recognition of scientific assessments carried out by Member States authorities and EU institutions.
This is the first case related to the question of whether an authorized fixed combination medicinal product (Fumaderm) and a mono-substance medicinal product based on a component of that fixed combination (Tecfidera) belong to the same GMA for the purpose of applying regulatory data protection. The AG puts forward a strict interpretation of the GMA concept and rejects the extensive application adopted by the General Court in first instance. If followed by the Court of Justice it would mean that the regulatory data protection of Tecfidera and the EMA’s invalidation of the generic application of Polpharma is upheld. In what follows we will explain why we believe the AG is right:
The global marketing authorisation (GMA)
The GMA concept is set out in Article 6(1) of Directive 2001/83/EC and is aimed at preventing the prolongation of the regulatory data protection period for developments of an existing product. The provision establishes that any additional strengths, pharmaceutical forms, administration routes, presentations or variations and extensions shall be viewed as part of the same GMA and therefore not entitled to additional regulatory data protection.
In its Opinion, the AG states that the developments listed in Article 6(1) are listed in an exhaustive manner. Thus, the GMA concept does not apply to changes to medicinal products that constitute a modification to their qualitative composition in terms of active substances.
This conclusion is relevant in the current case given the particular characteristics of the products concerned: Tecfidera is a product containing dimethyl fumarate (DMF), authorized in 2014 to Biogen and intended for the treatment of multiple sclerosis. Biogen is also the current holder of a marketing authorization for Fumaderm, a fixed combination product containing DMF and monoethyl fumarate (MEF), authorized in 1994.
Based on the wording of Article 6(1), the AG concludes that “the concept of ‘global marketing authorization’ does not apply to changes to medicinal products that constitute a modification to their qualitative composition in terms of active substances. Rationally, that applies to a mono-substance medicinal product, composed of one active substance, and a fixed-combination product, composed of at least two active substances with different moieties. A comparison of their qualitative compositions therefore appears to be a suitable methodology for the purposes of determining whether those two medicinal products fall under the same global marketing authorization pursuant to the second subparagraph of that provision.” (Paragraph 64)
From this interpretation it follows that Tecfidera and Fumaderm do not belong to the same GMA and therefore Tecfidera was entitled to its own period of regulatory data protection, separate from Fumaderm’s. The EMA was therefore right to refuse Polpharma’s generic application as it was still under protection at the time the application was submitted.
To Polpharma’s argument that a literal interpretation carries the risk of undermining the objective of GMA (i.e., to prevent the prolongation of the regulatory data protection period of an existing product on the basis of mere variants undeserving of its benefit) the AG responds that “competent authorities must be assumed to be capable of dealing with flawed or abusive applications” (paragraph 74).
Mutual recognition of scientific assessments
Fumaderm was first authorized by BfArM (Germany) in 1994. Tecfidera was authorized by EMA, and the application for a generic of Tecfidera was also submitted before EMA.
At first instance, the General Court considered the Commission should have asked EMA to verify the therapeutic effect of MEF (one of Fumaderm’s two active substances) within Fumaderm. The AG disagrees and, in doing so, reflects on the principle of mutual recognition enshrined in EU pharmaceutical legislation. The AG concludes that “not only Member State authorities, but also European Union bodies, should be obliged to recognize the previous scientific assessments relating to a given medicinal product, unless there are specific reasons related to public health – for instance, doubts surrounding the safety of the product – that would result in the triggering of a new assessment. As already indicated, that consideration relies on the existence of the same legislative and regulatory framework, which is intended to lead to the same outcome and that eliminates, for this reason, the need to verify the previous assessment of competent authorities.” (Paragraph 106)
According to the AG, the principle of mutual recognition prevented the EMA and EC from “verifying the therapeutic relevance of MEF within Fumaderm, given that that would entail reassessing the qualitative composition of that medicinal product, for which a market authorization had been granted by the BfArM.” (Paragraph 107).
The AG expands that BfArM renewed the marketing authorization of Fumaderm in 2013 and at that occasion had to assess the therapeutic contribution of MEF to the fixed combination in accordance with the current scientific guidelines. Based on applicable law the BfArM would have had to refuse the renewal in case MEF had no demonstrated contribution to a positive assessment of Fumaderm. As such the AG backs up the argument that the competent authorities are equipped to deal with potential abusive applications.
Based on the above considerations, the AG suggested that the CJEU should set aside the General Court’s 2021 judgment and dismiss the action for annulment brought by Polpharma at first instance. In other words, that EMA’s decision refusing to validate Polpharma’s generic application should stand.
Observations on AG opinion
The AG’s Opinion is not binding on the CJEU and we will need to await the final decision of the Court of Justice. However, in our view the arguments of the AG should be followed in that:
- Following Polpharma’s approach of GMA would in this case lead to an overreach by EMA and the Commission over national authorities competencies. More generally, it is incompatible with the principle of mutual recognition which is a cornerstone of the EU regulatory system;
- The EU regulatory framework (and its implementation in national law) has already mechanisms that avoid abuse of regulatory data protection.