On 15 September 2015, the General Court delivered its judgment in Case T-472/12, Novartis Europharm v European Commission (supported by Teva). Novartis was challenging a marketing authorisation (MA) granted to Teva under the “abridged” application procedure for the authorisation of generic products. Novartis held MAs for two products authorised via the “centralised” procedure; both products contained the active substance zoledronic acid. The first to receive its MA was Zometa, authorised in March 2001 for a number of oncology indications; the second product, Aclasta, was authorised in different indications (and at a different, indication-appropriate strength) in April 2005. In filing an application for a generic zoledronic acid product with indications corresponding to those of Aclasta (but not those of Zometa), Teva sought to cross-refer to the data in the files of both Novartis products, on the basis that neither benefitted from ongoing regulatory data protection (RDP) by the data of its application (May 2011). The European Commission agreed with Teva, and granted an MA for the generic product. In challenging the grant of the Teva MA, Novartis claimed that data in the Aclasta file was still covered by RDP as Aclasta did not fall within the “global marketing authorisation” (GMA) of Zometa, and thus it was not possible for Teva to cross-refer to this data to obtain its MA. The GMA concept was introduced into the pharmaceutical legislation fairly recently (through amendments made in 2004 to the main Directive 2001/83/EC) and although elaborated on by the European Commission in its “Notice to Applicants” guidance, this is the first opportunity that the General Court has had to confirm that interpretation.

In dismissing the action, the General Court has followed previous case law and backed the Commission’s interpretation of the legislation, maintaining the positon that the opportunities for an innovator company to gain independent protection of regulatory data filed in support of developments or improvements to a particular authorised product are very limited.

Regulatory Data Protection and the Global Marketing Authorisation concept

For medicinal products authorised under the “centralised” authorisation route (rather than by national regulatory agencies), the period of RDP applicable, for products authorised at the time of grant of both the Zometa and Aclasta MAs, was 10 years. In other words, a generic applicant could not ask the regulatory authority to cross-refer to the data contained in an innovative product’s dossier for the purposes of granting a generic MA for a period of 10 years from the date of first grant of that product’s MA (this concerns the so-called “abridged” procedure whereby the generic company has a right to rely on certain innovator product data after RDP expiry to supplement its own more limited data). The RDP provisions have since been amended in the 2004 amendments to the legislation (taking effect from late 2005 for the purposes of these changes), but for the purposes of this case a straightforward 10 years of RDP was applicable. There was no argument about whether the RDP for Zometa (authorised in March 2001) had expired when Teva filed its abridged application in May 2011, but Teva also sought to rely on the Aclasta data (authorised April 2005) under the GMA concept, as set out below. On the other hand, Novartis argued that Aclasta was protected by a separate period of RDP which was still running when Teva made its MA application.

While the length of RDP is specified in legislation, its scope, in terms of whether improvements or developments to the original product benefit from their own, independent period of RDP, is something which has been clarified by the European Courts in case law, and then set out in a legislative provision, since 2004. That provision is Article 6(1), second subparagraph of Directive 2001/83/EC, as amended, which consolidated existing case law as legislation as follows:

"When a medicinal product has been granted an initial marketing authorisation in accordance with the first subparagraph, any additional strengths, pharmaceutical forms, administration routes, presentations, as well as any variations and extensions shall also be granted an authorisation in accordance with the first subparagraph or be included in the initial marketing authorisation. All these marketing authorisations shall be considered as belonging to the same global marketing authorisation, in particular for the purpose of the application of Article 10(1) [the abridged application procedure]."

According to the explanation of the scope of the GMA provided in the European Commission’s “Notice to Applicants” guidance (Volume 2A, Chapter 1):

 ".... the global marketing authorisation contains the initial authorisation and all variations and extensions thereof, as well as any additional strengths, pharmaceutical form, administration routes or presentations authorised through separate procedures, including in different Member States within the EU, and under a different name, granted to the marketing authorisation holder of the initial authorisation"

Thus, under the GMA concept (as well as according to case law), it is generally not possible to extend existing periods of protection, or to secure a new period of protection for additional regulatory data filed in support of a variation (such as a new therapeutic indication) or extension (such as a new strength), for an active substance that is already the subject of an MA held by the same MA holder. The fact that a new, stand-alone authorisation or a different authorisation procedure or product name is involved does not make any difference to this, according to the Notice to Applicants.

Key points of the judgment

The Commission contended that, applying the GMA concept as set out above, Aclasta fell within the scope of the Zometa GMA and thus was not entitled to independent RDP (i.e. the RDP for both Zometa and Aclasta expired in March 2011). Novartis argued that Aclasta did not form part of the Zometa GMA and that the data in the file was still protected.

In dismissing the action, the Court first noted that although Zometa and Aclasta concerned different indications and strengths, and Aclasta was in fact authorised under a separate “centralised” procedure, Novartis could have authorised these new strengths / indications by way of a variation / extension to Zometa, since according to the Variations Regulation, the addition of a new therapeutic indication is a “Type II variation” and a change in strength or addition of a new strength is regarded as an “extension” under the same legislation. Contrary to the position taken in the Notice to Applicants, Novartis claimed that the fact that Aclasta was authorised under a separate procedure and with a separate trade name meant that it did not form part of the Zometa GMA since the GMA concept is confined to variations / extensions authorised in accordance with the Variations Regulation which are included in the terms of the first MA granted for the original product. On the other hand, the GMA concept does not cover developments authorised by separate MAs (as Aclasta had been), Novartis argued. In response, the Court noted that it is settled case law that in interpreting a provision of EU law, it is necessary to consider both the wording and the context in which it occurs and the objective pursued by the rules of which it is part. Since the relevant wording of Article 6(1) does not make any distinction between a development of the original product authorized through an amendment of the terms of the initial MA and one authorized through the grant of a separate MA, it must be that the original product and any additional strengths, pharmaceutical forms, administration routes, presentations, variations and extensions form part of the same GMA for the purposes of the RDP provisions in either case.

Furthermore, no legislative provision specifically determines the cases in which a development of a medicinal product should be authorised by means of a variation of the terms of the initial MA, or on the other hand the cases in which such a development should be authorised by the grant of a separate MA. That being the case, when Novartis developed Aclasta it was entitled to choose between either applying for a variation / extension to Zometa or seeking a separate MA with a new trade name, in order to secure an MA for the new indication/strength. In order to justify its choice of route, Novartis argued (in a letter to the regulator) that “the posology, expected safety profile, target prescribers etc. [for the Aclasta indications] would be very different from those in the oncology settings”, and so it intended to seek a separate MA in order to “differentiate the use of the product in these two settings, especially to avoid misinterpretations of the PIL information by patients”. However, the Court noted that, as Advocate General Jacobs had already observed in his opinion in Novartis Pharmaceuticals (C106/01), the market strategy of an undertaking cannot affect the application of the RDP period of one and the same active substance, because to “exclude the application of the [judgment in Generics (UK) and Others …..] whenever a subsequently authorised variant of a reference product had been given a new designation would elevate form over substance, and would create an easy route for applicants to gain additional data protection in circumvention of Generics (UK) and Others”.

The arguments put forward by Novartis were, the Court held, “clearly at odds with the objectives pursued by the legislation under consideration, as clarified in particular by the case law of the Court of Justice”. Had they been accepted by the Court, innovators would (by obtaining a new, stand-alone MA) have a means of securing a new period of protection for additional regulatory data filed in support of, for example, a new indication and strength for an active substance that is already the subject of an MA held by the same MA holder; this would be contrary to the purpose and effect of the line of case law in this area, as well as to the GMA concept introduced into the legislation to consolidate that case law.

The Court also noted that a change to the legislation in 2004 to allow for an additional 1 year RDP in the case of development of a new indication in certain circumstances was at variance with the applicant’s position, since this new provision would be “pointless” if a further 10 years RDP was available instead, simply by applying for a separate MA.

As it has done in other cases, the Court also made reference to the wording of the Notice to Applicants guidance (as quoted above), “which, while not legally binding, may provide a helpful reference point for a judicial assessment”.

A number of further arguments put forward by Novartis, to the effect that the application of RDP rights to products differs according to whether they are authorised in accordance with the centralised or national procedures, were also rejected by the Court. The Court dismissed the action, concluding that since Aclasta constitutes an additional strength and a variation (new therapeutic indication) in comparison with Zometa, the situation clearly falls within the scope of Article 6(1) and thus Aclasta falls within the GMA of Zometa, allowing Teva to cross-refer to data in both files. To have found otherwise would have made for a surprising judgment, given that Novartis was asking the Court to deviate quite dramatically from the existing line of case law based on well-established reasoning and objectives, as well as to rule against the Commission’s interpretation of the GMA concept, which is in line with the objectives of the RDP framework as explained in the case law.