Regulatory exclusivity rights: the General Court annulled the decision of EMA to not accept a marketing authorization application

On May 5 2021 the General Court published a (lengthy) judgement in which it annulled the decision of EMA to not validate (and thus not accept and review) a marketing authorization application (“MAA”) for a generic version of a medicinal product containing dimethyl fumarate (“DMF”) (case T-611/18, ECLI:EU:T:2021:241).

Background of the case

To understand the background of the case, we must go back to the year 1994. In that year the authorities in Germany granted a national marketing authorization (“MA”) for a medicinal product containing both DMF and various monoethyl fumarate salts (“MEF”). The medicinal product was named Fumaderm and was indicated for the treatment of psoriasis.

In 2006, Biogen acquired the company holding the Fumaderm MA, after it had previously obtained a license to exclusively develop and market products containing DMF.

A couple of years later, in 2011, Biogen approached the EMA to discuss the possibilities to request a central MA for a medicinal product named Tecfidera, containing (only) DMF, for the treatment of multiple sclerosis and in 2012 Biogen submitted a full application for Tecfidera (on the basis of article 8(3) of Directive 2001/83).

After various discussions between the European Commission, (members of) the Committee for Medicinal Products for Human Use (“CHMP”) and Biogen about the status of DMF, the European Commission granted Biogen in 2014 a central MA for Tecfidera (DMF) for the treatment of multiple sclerosis. It was included in the implementing decision of the European Commission that Tecfidera (DMF) and Fumaderm (DMF + MEF) did not belong to the same global marketing authorization. As a consequence, Tecfidera would benefit from regulatory data and market protection (8 +2 years).

Despite the statement in the decision that Tecfidera did not belong to the same global marketing authorization, Pharmaceutical Works Polpharma submitted a MAA for a medicinal product containing DMF in 2018. It entailed a generic application (article 10(1) of Directive 2001/83), whereby reference was made to the dossier of Tecfidera.

This MAA was not validated by EMA (i.e. not accepted and thus not reviewed) as EMA stated that the eight-year period of data protection that Tecfidera benefited from had not yet expired. Therefore the application could not be validated (taking into account article 14(11) of Regulation No 726/2004).

Polpharma disagreed with the decision of EMA to not validate the generic MAA for a medicinal product with DMF as the active substance. Polpharma disputed that Tecfidera benefited from a data (and market) protection period of 8 + 2 years and argued that the MA for DMF fell under the scope of the global marketing authorization of the existing medicinal product containing DMF + MEF.

Some highlights of the outcome of the case

  • The Court agreed with the statement of Polpharma that Tecfidera could not benefit from data- and market protection as Tecfidera (DMF) fell under the scope of the existing global marketing authorization for Fumaderm (DMF + MEF). The Court ruled that the European Commission made a manifest error of assessment in concluding that the medicinal product Tecfidera (containing DMF) was not covered by the same global marketing authorization as Fumaderm (containing DMF + MEF). The fact that a full dossier was submitted (article 8(3) of Directive 2001/83) for the MA of Tecfidera did not have an effect on the scope of a global marketing authorization. Therefore, there was no data exclusivity period applicable at the time and EMA should have validated a MAA for a generic version of Tecfidera, whereby reference was made to data of the Tecfidera dossier as the reference medicinal product.
  • The Court reaffirms (in line with EU:C:2017:498) that the global marketing authorization covers subsequent developments, irrespective of their authorization procedure.
  • According to the Court, the principle of mutual recognition cannot (as EMA tried to argue) prevent the CHMP from examining the assessments previously carried out by a national authority or from carrying out an independent assessment, following the submission of a MAA under the centralized procedure.
  • It cannot be held against Polpharma that they have not objected against the decision of the European Commission of 30 January 2014 to grant the MA for Tecfidera, as in that point in time it was not clear enough that Polpharma could object against that decision.
  • The ruling gives a nice peek into the discussions that took place beforehand between the European Commission, (members of) the CHMP and Biogen. It is clear that this topic was not easily decided on and was subject to some serious going back and forth about whether or not DMF should be seen as a “new active substance” and/or was covered by the same global marketing authorization (especially considerations 16-38).

Should there be more possibilities for regulatory exclusivity for new indications?

The current system often creates an “all” or “nothing” situation in terms of regulatory exclusivity rights, as is also shown by the ruling. The new indication for Tecfidera (MS) differed greatly from the existing psoriasis indication of Fumaderm. So, although the active substance itself was not a new active substance it is clear that additional research was needed to receive approval for the indication MS. Therefore, you could debate whether it would be beneficial if there would be a certain degree of space for authorities to tailor the period of exclusivity to the level of innovation.

Though, under the current system, there are already some possibilities to receive regulatory exclusivity rights for new indications (leaving exclusivity for orphan medicinal products aside):

  • Under article 10(5) of Directive 2001/83, one year of exclusivity can be granted if a new indication is introduced for a well-established active substance;
  • Under article 10(1) last paragraph of Directive 2001/83, one additional year of exclusivity (8+2+1) can be received if during the first eight years of the data exclusivity period an authorization is obtained for one or more new indications that bring(s) a significant clinical benefit in comparison to existing therapies.

Nonetheless, the use of these options seems in practice (very) limited. This may also be triggered by the fact that the period of one year is relatively short and/or by the fact that on a national level off-label use (outside the approved indications) of medicinal products is often possible, meaning that there is a risk that the exclusivity for the indication is in practice not fully benefitted from.

When looking at the options for exclusivity for new indications in the current case, it is clear that the latter option could not play a role at the time of the application for Tecfidera. The first option is also not discussed or addressed as part of the ruling. However, in hindsight the question could be raised  whether DMF could – back in 2014 – qualify as a well-established substance that might have been eligible to receive a one-year period of exclusivity for the introduction of the new indication (MS). This seems not evident as DMF was at that time not separately approved.

Last notes

Overall, the ruling shows in my view that the system around data- and marketing protection periods is not always fully ready for all the permutations that may occur in practice. This leads to complex and lengthy legal discussions and uncertainty. Under the current regulatory system there is also little to no room to look into the level of actual innovation in view of the protection that will be granted. I am curious whether this ruling will play a role in future discussions about granting (data) protection, especially in relation to new indications and in relation to the length of such data protection period.


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