Marketing authorisation: the right to challenge

Since the EU regime of data exclusivity for pharmaceuticals was amended in late 2005, in large part to reflect Court of Justice of the EU (CJEU) case law in the 1990s and early 2000s, there has been little case law on the interpretation of the new legislation. This situation is now starting to change.

In order to secure a marketing authorisation (MA) for a new medicinal product, in addition to demonstrating satisfactory quality, applicants must file extensive clinical and non-clinical data to support its safety and efficacy in accordance with article 8(3)(i) of Directive 2001/83/EC, as amended by Directive 2004/27/EC.

According to article 10, an application for a generic MA of a medicinal product previously authorised under article 8 can be sought eight years after the first MA in the EU for the active substance in the ‘reference medicinal product’, but such a generic MA cannot take effect until ten years after the first MA for the active substance.

This period is extended to 11 years if the first applicant secures an MA for a new indication for the medicinal product in question during the first eight years, and the new indication is determined, during the scientific evaluation before its authorisation, to bring “a significant clinical benefit in comparison with existing therapies” (thereby giving rise to the ‘8+2+1’ characterisation of the EU data exclusivity rules).

However, there is also another route to securing an MA for a pharmaceutical and it is this other route—under article 10a of the directive, involving demonstrating safety and efficacy through “well-established medicinal use”—which has been the source of much controversy over the years.

This route, which was retained in the 2005 amendments, relieves the MA applicant from having “to provide the results of pre-clinical tests and of clinical trials if he can demonstrate that the active substances of the medicinal product have been in well-established medicinal use within the EU for at least ten years, with recognised efficacy and an acceptable level of safety”. Such demonstration is achieved by reference to published literature.

Earlier controversies surrounding this particular route for securing an MA involved attempts to use it to undermine data exclusivity. One occurred more than 20 years ago, in case C-440/93 Scotia, and another in 2010—long after the “at least ten years” qualification was introduced into article 10a—in a situation giving rise to the final warning that the European Commission gave to Germany for the actions of its competent authority.

The actions in question involved taking less extensive use of the active substance, such as in clinical trials, into account in determining the period of well-established medicinal use, and “thereby obscuring the clear separation between different authorisation procedures”.

However, case T-301/12, Laboratoires CTRS v Commission, did not concern an attempt to undermine data exclusivity and here the commission’s attempt to prevent the use of the article 10a route to secure an MA for an orphan medicinal product that had by its nature received only relatively limited use was successfully challenged.

A new approach

A decision of the CJEU on October 23, 2014—in the case C-104/13, Olainfarm v Latvijas Republikas Veselības Ministrija—has revisited the article 10a route to securing an MA in yet another context, but it is of wider significance than for the article 10a route alone. In this case the CJEU has established that a medicinal product authorised on the basis of well-established medicinal use can itself be used as a reference product for the purposes of applying for a generic MA.

More significantly, however, it has also confirmed that the holder of an MA for a reference medicinal product has the right to challenge the decision of a competent authority granting a generic MA on the basis of such a reference medicinal product.

The reference to the CJEU giving rise to this decision arose out of an application by Olainfarm to annul an MA that had been granted by the competent authority in Latvia to a competitor, Grindeks. In 2003, before Latvia acceded to the EU, Olainfarm had secured an MA for the medicinal product Neiromidin (ipidacrinum). Its application for the MA had been made under the applicable national legislation at the time, which corresponded only in part to EU law governing the authorisation of medicinal products.

Therefore once Latvia had acceded to the EU, Olainfarm had to seek a new MA for Neiromidin under EU law, which it did in 2008, on the basis of well-established medicinal use. Grindeks then secured an MA for the same product, basing its application not on well-established medicinal use (which it would have been open to do) but instead as a generic of Olainfarm’s Neiromidin as a reference product.

"there is nothing to preclude such a medicinal product from being used as a reference product for the purpose of obtaining a MA for a generic product."

Olainfarm challenged the grant of the generic MA to Grindeks before the competent authority in Latvia on the basis that it had been made while the reference product was protected by data exclusivity. The authority considered, however, that the holder of a MA for a reference medicinal product does not enjoy an individual right to challenge an MA granted for a generic of the reference product.

An initial appeal was unsuccessful, but on the subsequent appeal questions were referred to the CJEU regarding (1) whether the manufacturer of a reference medicinal product has an individual right to bring an action challenging the decision of a competent authority to grant an MA for the generic medicinal product; and (2) whether a medicinal product for which an MA had been secured in accordance with article 10a of the directive on the basis of well-established medicinal use could be used as a reference medicinal product for the purpose of an application for a generic MA under article 10.

The need for the second question arose because article 10(2)(a) defines, for the purposes of article 10, a reference medicinal product as “a medicinal product authorised under article 6, in accordance with the provisions of article 8”. On a literal interpretation, this definition does not cover a medicinal product that has been authorised in accordance with article 10a.

However, the CJEU, observing that the dossier for the MA granted for a medicinal product under article 10a will contain all the information and documents needed to demonstrate the safety and efficacy of the product, held that there is nothing to preclude such a medicinal product from being used as a reference product for the purpose of obtaining a MA for a generic product.

The consequence of this is to, in effect, confer data exclusivity on an MA so secured, although the practical effect of this in preventing others from securing an MA during the protected period will be limited as the article 10a route will usually be available also to them.

The need for the first question arose because under Directive 2001/83/EC the procedure for the granting of an MA is “conceived as a bilateral procedure involving only the applicant and the competent authority”. As the CJEU observed, the directive contains no express provision that a decision of the competent authority granting an MA for a generic product can be challenged by the holder of an MA for the reference product.

However, the CJEU also observed that article 47 of the Charter of Fundamental Rights of the EU required that any person whose rights as guaranteed by the laws of the EU have been violated has the right to an effective remedy before a tribunal. Therefore it went on to find that the holder of an MA for a medicinal product used as a reference product by a generic applicant has the right to a judicial remedy to challenge a decision to grant a generic MA provided that such a holder of the reference product MA is seeking judicial protection of a right conferred on it by article 10, namely the right of data exclusivity.

The significance of the CJEU judgment is much wider than the specific circumstances of this case. It is of relevance to any challenge mounted by the holder of an MA to a reference product in the EU against the grant an MA for a generic version of such reference product.

Although in practice such challenges have never presented a problem of standing in some countries of the EU, such as the UK, national systems of administrative law and the requirements of standing under it are highly variable throughout the EU.

Many countries have in the past shared the approach of the Latvian courts in this case, in considering that the holder of an MA to a reference product does not enjoy an individual right to challenge an MA granted for a generic version of the reference product. This decision establishes that this is not the case, and so should make it easier to challenge such MAs in the future.

Trevor Cook is a partner at Wilmer Cutler Pickering Hale and Dorr. He can be contacted at: trevor.cook@wilmerhale.com