The Court of Justice of the European Union (CJEU) recently gave judgments in Novartis Europharm v European Commission (Cases T-472/12 and T-67/13)

The CJEU held that where a marketing authorisation holder has developed its medicinal product (e.g. by developing a different strength, pharmaceutical form, administrative route or presentation), the developed product will share the regulatory data protection period of the original product, even where the developed product holds a separate marketing authorisation. Generics manufacturers may use the data once that period has expired.

Background

Under EU Directive 2001/83 (and under Directive 65/65 which preceded it), in order for a medicinal product to be granted a marketing authorisation, applications for an authorisation for a new active substance must be accompanied by the results of pre-clinical tests and clinical trials.

For a medicinal product authorised before the end of 2005, following the grant of a marketing authorisation the manufacturer received the benefit of a 10-year regulatory data protection period.

The relevance of the data protection period is that, once the data protection period of a medicinal product (the reference product) has ended, a manufacturer of a generic (or essentially similar) medicinal product is not required to provide its own clinical trial data in order to obtain a marketing authorisation, but can rely on clinical trial data relating to the reference product.

During the data protection period, the manufacturer of a reference product has security that generic manufacturers cannot apply for marketing authorisations in relation to that product.

Article 6(1) of Directive 2001/83 provides that, where a medicinal product has obtained a marketing authorisation, any development of the product (such as a different strength, pharmaceutical form, administrative route or presentation) must also be authorised. The developed product may either be included in the initial marketing authorisation or be granted its own separate authorisation. Article 6(1) then continues:

'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)'.

Article 10(1) of Directive 2001/83 sets out the current provisions in relation to the regulatory data protection period[1].

Facts of the case

The claimant in both cases was Novartis Europharm Ltd, which holds the marketing authorisations for the medicinal products Zometa and Aclasta. Both products contain the active substance zoledronic acid. Zometa was granted a marketing authorisation in March 2001 relating to a number of oncology indications. Aclasta extends the use of the zoledronic acid to new non-oncology indications (such as osteoporosis) with a different strength appropriate for those indications. A separate marketing authorisation was granted for Aclasta in April 2005.

In 2012 the European Commission granted marketing authorisations to Teva Pharma BV and Hospira UK Ltd for two generic medicinal products, which both used Aclasta as the reference product. Both applicants relied on the data used by Novartis in its applications for Zometa and Aclasta in their own applications.

Novartis challenged the decisions to grant these marketing authorisations before the CJEU, asking the CJEU to annul them both. Novartis argued that the marketing authorisations were unlawful because they infringed Aclasta's regulatory data protection period.

It argued that Aclasta's 10-year data protection period began to run from 2005, when it was granted a marketing authorisation. In particular, the 'global marketing authorisation' referred to in Article 6(1) should not cover development products with a separate marketing authorisation and a new name (such as Aclasta). Alternatively, Novartis argued that where a development product is authorised through the centralised procedure (administrated by the European Medicines Agency (EMA)) rather than through a national procedure, the product does not fall within the global marketing authorisation.

Under either argument, Aclasta did not form part of the same global marketing authorisation as Zometa and attracted an independent data protection period, which would run until 2015.

The Commission (supported by the intervention of Teva and Hospira in their respective cases) argued that the marketing authorisation for Aclasta is included within the global marketing authorisation granted for Zometa and that Aclasta did not enjoy an independent data protection period. On this basis, the data protection period for Aclasta expired in 2011 and the decisions were lawful.

The question to be addressed by the CJEU was whether Zometa and Aclasta were covered by the same global marketing authorisation and so the same data protection period.

The decision

The CJEU rejected Novartis' arguments on the effect of the separate marketing authorisation, giving three key reasons.

First, it was clear that the wording of Article 6(1) makes no distinction between where a developed product is included in the initial marketing authorisation, and where the developed product is granted a separate marketing authorisation. On the wording used, in both cases the original product and the developed product will form part of the same global marketing authorisation for the purpose of the regulatory data protection period. This means that a global marketing authorisation may encompass, formally, a number of separate authorisations.

Second, Novartis could have obtained a variation of the marketing authorisation for Zometa instead of applying for a new marketing authorisation. Novartis had made a commercial decision to apply for a new authorisation and to apply a new name to the product to avoid confusion between the two products and their intended uses. The CJEU considered that to allow an undertaking's marketing strategy to affect the application of the data protection period would provide an easy route for undertakings to gain additional data protection and this would circumvent the principles underpinning the law.

Third, the CJEU considered the approach adopted by Novartis to be at odds with the objectives pursued by the legislation, and relevant case law. The data protection period balances the protection of research and development work undertaken by innovative pharmaceutical companies (on the one hand) with the wish to avoid excessive testing on humans and animals (on the other). It also acknowledges that the abridged procedure for marketing authorisations can save considerable time and expense. An approach whereby a regulatory data protection period could be extended through a development (authorised by the grant of a separate marketing authorisation) would clearly jeopardise those objectives.

The CJEU noted that, since the grant of a marketing authorisation for Aclasta, the law has been amended to extend the protection period during which generic products may not be marketed by a year in certain cases where the market authorisation holder obtains an authorisation for new therapeutic indications which are considered to be beneficial. The possibility of this extension would be pointless if an applicant could obtain a separate marketing authorisation for new indications and automatically receive an additional 10-year protection period.

In relation to Novartis' alternative argument, relating to authorisation under the centralised procedure, the CJEU also rejected this argument - the same protection should apply, regardless of the procedure which was used.

The CJEU concluded that the situation in the two cases was exactly the type of situation referred to in Article 6(1) of Directive 2001/83 (as quoted above). Aclasta constituted an additional strength and a variation, consisting of new therapeutic indications, by comparison with Zometa, and must therefore be included in the global marketing authorisation for Zometa.

It followed that Zometa and Aclasta shared the same regulatory data protection period. The Commission was entitled to permit Hospira and Teva to refer to the data used for the marketing authorisation of Zometa and Aclasta in their applications for a marketing authorisation.

Commentary

The CJEU was clear that the Commission's decisions to grant marketing authorisations for the two generic products were consistent with both the wording of the relevant legal provision and the intention behind that provision.

That Article 10 of Directive 2001/83 now makes express provision for a protection period to be extended in limited circumstances further strengthened the CJEU's view that it cannot be extended in broader circumstances.

One of the arguments made by Novartis was that innovations to improve or develop a medicinal product which has been granted a marketing authorisation may require further investment. The CJEU was clear that it was for the EU legislature to determine the policy on the extent to which such innovation should be given further protection; it had done so and the policy did not entitle Novartis to the protection which was requested.

We note that the CJEU's consideration of these cases was the second time in 2015 that it has given judgment on matters relating to protection periods for medicinal products. At the start of the year, it gave judgment in Teva Pharma BV v EMA (Case T-140/12); in that case holding that the EMA was entitled to refuse to grant a marketing authorisation in relation to a generic medicinal product because the protection period for the reference product had not expired. Importantly, in that case the reference product was an orphan medicinal product and the judgment highlights the point that different legal provisions are applicable for the protection periods of such products.

Footnote

[1] Article 10(1) of Directive 2001/83 now provides for an 8-year data protection period and a 10-year period following authorisation of the reference product during which a generic product cannot be marketed. This 10-year period can in some cases be extended to 11 years where the market authorisation holder obtains an authorisation for new therapeutic indications which are considered to bring significant clinical benefit.