Jordi Faus of Faus & Moliner highlights the importance of the ECJ to the standing of European pharmaceutical law through the Olainfarm case.
A distinctive feature of pharmaceutical law is the relevance of judgments issued by the Court of Justice of the European Union (ECJ). Amid an increasingly overwhelming number of rules and “soft” legislative instruments, the rulings of the ECJ have shaped many of the rights and expectations of companies operating in the pharmaceutical market in Europe. It may be that in some cases the ECJ has avoided tackling some especially conflicted issues, but in general one may conclude that European pharmaceutical law, as it stands today, owes much to the judges seated in Luxembourg and to those who had the patience and the courage to bring matters to their attention. The Olainfarm case is one of these cases – one which also merits being labelled a leading case.
The facts of the case
In 2003, Olainfarm A/S (Olainfarm) obtained approval to market Neiromidin in Latvia under national rules which, at that time, corresponded only partially with applicable Community law. In 2008, Olainfarm obtained a marketing authorisation (MA) for the same product under the so-called “well-established use” exemption in accordance with Article 10a of Directive 2001/83. This provision allows applicants not to provide the results of pre-clinical tests or clinical trials if they can demonstrate that the active substances of the medicinal product have been in well-established medicinal use within the Community for at least ten years. In that event, the test and trial results may be replaced by appropriate scientific literature.
In 2011 a competitor of Olainfarm, Grindeks AS (Grindeks), obtained an MA for a generic medicinal product, having indicated in its application that Neriomidin was the reference product. In order to obtain such MA, Grideks filed an application claiming that its product had the same qualitative and quantitative composition in active substances and the same pharmaceutical form as Neriomidin, and that both products were bioequivalent.
Olainfarm filed an administrative appeal against the granting of the MA to Grideks. This appeal was rejected on the grounds that the holder of an MA for a reference medicinal product does not enjoy an individual right to challenge an MA granted for a generic of the reference product. Olainfarm then instituted judicial proceedings and the Senate of the Supreme Court of Latvia decided to send two very specific questions to the ECJ for a preliminary ruling.
In essence, through the first question, the Latvian Court wanted the ECJ to rule on whether Directive 2001/83 granted the holder of an MA for a reference product the right to a judicial remedy, the object of which would be to determine whether the conditions established by Article 10 of the Directive had been respected or not by the competent authority when granting the MA for the generic product.
As regards the second question, the Latvian Court asked the ECJ to rule on whether a medicinal product approved in accordance with Article 10a of Directive 2001/83 on the basis of the “well-established use” exemption could be considered as a reference product for the purposes of the approval of a generic or not.
A well-established medical use
The ECJ dealt first with the second question, which I think was not an at all an easy one if we go back to the fundamental principles that apply to generic approvals. One of the reasons generic applicants may benefit from an abridged procedure for their products is to avoid the repetition of trials in humans. In the case of products approved on the basis of the “well-established use” exemption, the applicant does not carry out such trials, but relies on scientific literature to support its petition. In my view, it would seem strange that an applicant who could obtain an MA by compiling the appropriate literature by itself would be given the opportunity to skip this work by carrying out a bioavailability study in humans. Contrary to what AG Wahl states in his opinion, allowing the reference to the product approved on the basis of the “well-established use” exemption will require tests on humans to show bioequivalence to a product which was approved without its holder having filed the results of any trials.
Well, the ECJ went the other way and ruled that medicines approved on the basis of the “well-established use” exemption may qualify as reference products. In its reasoning, the ECJ relies, in particular, on the idea that these products have proven their efficacy and safety in a full manner on the basis of a dossier containing all the information and documentation needed for providing such evidence. Therefore, the ECJ understands that national authorities should be able to approve a generic of such products if the applicant complies with all the conditions established in the directive.
A bilateral procedure
In connection with the second issue, the judgment is also highly interesting.
First of all, the ECJ confirms that EU law does not create any right of the holder of the MA for a reference product to intervene in the administrative procedure, as followed by regulatory agencies when assessing any application that may be filed for a generic version of such product. The administrative procedure, the ECJ says, is conceived as a bilateral one involving only the applicant and the competent authority.
It is worth noting that the ECJ does not tackle the issue of whether a holder of an MA for a reference product may obtain some information as to the existence of applications for generics of its product or not. The fact that the procedure is a bilateral one may well mean that the holder of the MA for the reference product does not have the right to request access to the dossier filed by the generic competitor, or to file allegations against such application; but this should not per se impede an individual from obtaining some information about the activity that the regulator may be carrying out in connection with a given medicinal product, nor necessitate the individual to show a specific legitimate interest.
This is an area where rules and administrative practice differ across the EU. For example, in Spain, France and the UK, the authorities consider the existence of an application confidential and will only disclose certain information once the decision to grant or refuse the MA has been taken. In the Netherlands, any citizen may request information on pending applications for MAs from the authorities, but the name of the applicant shall not be disclosed. In Germany, the holder of the MA for the reference product may obtain information about the filing of the application, and this may also include the name of the applicant. This is also possible in Italy, unless the applicant objects for confidentiality reasons and such objection is sustained.
A right to judicial review
Having said this, the ECJ rules, unequivocally, that the holder of the MA for a reference product must have the right to bring a court action against the approval of the generic.
In Spain, the ruling is likely to have a major impact given that administrative courts have systematically rejected locus standi to the plaintiffs in these cases, and this notwithstanding the fact that Spanish law and jurisprudence have evolved in recent times by requesting only that plaintiffs had a legitimate interest in the case (see Article 19.1 of Law 29/1998, and judgments of the Supreme Court of 28 April 2005, 2 July 1985, 26 July 1996, 20 January 2009 and 21 January 2011, among many others). In the past, plaintiffs only had locus standi if a specific legal provision granted them such right or if they were otherwise able to show a direct interest in the outcome of the case.
Despite this, when the Spanish National Court has been confronted with such a matter, it has ruled that the interest of the holder of MA for reference products is not sufficient because the damage it could suffer would not derive from the grant of the MA for the generic product, but rather from the effective commercialisation of such product in the market. This position has been held in various cases (10 July 2009, Servier v Cinfa re Diosmin; 24 November 2010, Astra v Ratiopharm et al re Quetiapine; and 26 December 2012, Italfarmaco vs Cinfa and Normon re Calcium Carbonate–Cholecalciferole).
The position taken by courts in Spain, and in other member states where locus standi may have been denied so far, shall have to be revisited in light of Olainfarm. In this respect, it is especially important to note that the reasoning of the ECJ departs from the idea that Directive 2001/83/EC does not contain any express provision to the effect that a judicial remedy is available to the holder of an MA granted for the reference product to challenge the decision of the competent authority. However, the EJC finds full support for its ruling in the Charter of Fundamental Rights of the European Union according to which any person has the right to file a court action if the rights that it holds under European Union law have been violated.
On the other hand, there are some member states where holders of an MA for reference products are granted locus standi, but where doubts may appear as regards the scope of activity of national courts when reviewing the grant of the MA for the generic product. For instance, in Germany and the UK, the courts have clearly accepted locus standi in cases where the grounds for appeal had to do with the respect of applicable data protection periods, but the full scope of the right to challenge has never been tested, for example, where the data protection has clearly expired and the allegation is that some other aspect of the abridged procedure has not been complied with.
The ECJ judgment in Olainfarm brings light into this issue also, broadening the matters which holders of MAs of alleged reference products may request to be reviewed by the administrative courts. Here, the position of the ECJ seems much influenced by the rationale behind article 10 of Directive 2001/83. If this provision lays down the conditions under which the holder of an MA for a product is required to accept that another company refers to its dossier for the purposes of obtaining the MA for a generic product, it is apparent that such provision, according to the ECJ, confers a concomitant right on the holder of the first MA to demand that the rights attaching to him by virtue of those conditions are observed.
The judgment goes on to say that the rights that the holder of the MA for any product may demand to be respected are not only those related to the respect of data protection periods. The ECJ, in this respect, does not follow the opinion of AG Wahl, who seems inclined to restrict the judicial review as a way to ensure that the entry into the market of generic competition would not be improperly blocked. The ruling of the ECJ avoids this discussion, and states that the judicial remedy must exist where the holder of the MA claims that his product is not to be used as a reference product for the purposes of granting the generic approval. Moreover, the ECJ also says that this is not the only situation where judicial remedy must be possible. The use of the expression inter alia in the ruling part of the judgment and in paragraph 40 must be read in light of paragraph 38, where the ECJ states that the holder of the first MA may also demand that its product is not to be used for the purpose of granting an approval to a product which does not fulfil the requirement, laid down in Article 10(2)(b) of Directive 2001/83, that it should be similar to the reference product in terms of its composition in active substances and pharmaceutical form. The ECJ does not refer, in paragraph 38, to demonstrating bioequivalence by appropriate bioavailability studies, but my view is that this should also be included within the possible scope of judicial review.