On 14 February 2019, the Court of Justice of the European Union ('CJEU' or the 'Court'; C 423/17; ECLI:EU:C:2019:125) ruled on the Dutch Medicinal Board's (College ter Beoordeling van Geneesmiddelen,'CBG') policy regarding the publication of the full package leaflets and summaries of product characteristics ('SmPC') of generic medicinal products, instead of publishing the requested skinny label version on its website.
In short, the CJEU held that the CBG's policy was in breach of Union law, as it does not have discretion over the assessment of such a request. In addition, the CJEU ruled that a request not to include indications protected by a patent results in a limitation of the scope of the marketing authorisation (also 'MA').
Generally, a national competent authority is obliged to publish the marketing authorisation together with inter alia the package leaflet and the SmPC1. In the past, the CBG has adopted a policy which was unique compared to respective authorities in different Member States.
Prior to 2009, the CBG published the carve-out version of package leaflets and summaries of product characteristics of generic medicinal products on its website upon request of the MA holder.
However, in these documents, the CBG had indicated with an asterisk that that the product contained the active ingredient and was also approved for indications not published. After 2009, CBG published the full label version of the SmPC and the package leaflet on the website.
In the printed version, the MA holder could publish a carve-out version. However, the MA holder was obliged to refer to the medical product database on CBG's website.
This database is also consulted by doctors or pharmacists. The CBG explained in the course of these proceedings that patient safety would be at stake if it did not publish the full information2.
Warner-Lambert Company ('WLC') was the patent holder of European Patent EP 0 934 061 ('EP 061') which covered the use of pregabalin for the treatment of, inter alia, neuropathic pain. The medicinal product Lyrica was also intended for the treatment of epilepsy, generalised anxiety disorder and neuropathic pain.
Before placing its generic version of Lyrica on the market, the generic manufacturer Aurobindo informed the CBG that it did not wish to include the indication concerning the treatment of neuropathic pain (which fell under the patent) from the package leaflet and the summary of product characteristics. The CBG refused.
Subsequently, WLC initiated interim relief proceedings with the District Court of The Hague against the State of the Netherlands. WLC claimed that CBG had directly infringed its patent, as it offers pregabalin for sale for a patented indication, and indirectly, in that it encourages third parties to engage in infringements. The WLC also argued that CBG's policies were contrary to Article 11 of Directive 2001/83.
The District Court ruled that, while the CBG did not infringe the WLC's patent (as it did not offer anything for sale), it did violate its duty of care. In this context, the District Court assessed CBG's obligations under the Directive 2001/83, inter alia Article 11, which will be discussed below.
The State of the Netherlands filed an appeal against this judgment and the WLC filed a cross-appeal. At the same time, the CBG changed its policy regarding the publication on the website. The full label version was still published, but with the addition of an asterisk followed by text stating that the respective indication fell under the scope of a patent:
'This indication is protected by a patent … of another marketing authorisation holder. Further information in this regard may be found on the CBG website, www.cbg-meb.nl.'
During the appeal proceedings, the Court of Appeal of The Hague decided to stay the proceedings and asked the CJEU for a preliminary ruling.
In a nutshell, the question to be discussed by the CJEU concerned the interpretation of Article 11 of Directive 2001/83 and whether a MA holder's notification not to include a patented indication results in the marketing authorisation not applying, or no longer applying, to the patented indications or dosage forms.
On the basis of Directive 2001/83, the CJEU highlighted a few important principles as a starting point of its reasoning. Firstly, a package leaflet and a summary of the product characteristics are part of a marketing authorisation. Secondly, the product covered in the marketing authorisation must fulfil the conditions as described in the product characteristics. Finally, amending the product characteristics without notifying the national authority is not permitted.
The CJEU stressed the importance of Art. 10 of Directive 2001/83, which exempts generic producers from submitting results of pre-clinical and clinical tests, provided the conditions in this article are met. A marketing authorisation for a generic product cannot extend to any other indications than the reference product.
Art. 11 (2) Directive 2001/83 provides the possibility to exclude indications or dosage forms from the reference product's summary of product characteristics, which were still covered by a patent at the time when a generic medicine was marketed.
Referring to its judgment in Olainfarm (C 104/13, 23 October 2014, EU:C:2014:2316), the CJEU reiterated that the rationale behind this provision was not to hinder generic products from entering the market prior to the expiry of any patents, potentially covering an indication of dosage form of the reference drug.
In light of this, the CJEU drew the conclusion that not including particular indications in the marketing authorisation results in a limitation of the scope of the marketing authorisation.
Additionally, the Court explicitly stated that the national authority did not have any discretion when dealing with a request not to include a patented indication:
'[…] By making use of the option given by the second paragraph of Article 11, the marketing authorisation applicant thus limits the scope of his application and the competent national authority does not have any discretion in that respect […]' (para. 43)
The direct consequences of this judgment are twofold: Firstly, the CBG is obliged to follow the request of the applicant/holder of the marketing authorisation with respect to the exclusion of patented indications. Secondly, the MA holder limits the scope of its marketing authorisation by filing such a request.
This could potentially result in an off-label use which is possibly in breach with national regulatory law3. In the Netherlands, for example, off label use can (under certain circumstances) be charged with an administrative penalty4.
In response to this ruling, the CBG has issued a press release stating that it was going to amend its policy5. The new policy will correspond to policies in other EU Member States. The MA holders will be approached and requested to adjust their product information, which will then be adjusted on the website. The package leaflet will not refer to the register on website.
This judgment is limited to the (regulatory) effects of a request for a skinny label. When placing this ruling in the context of the recent skinny label discussion in patent law, the question arises whether generic manufacturer must file such request in the first place in light of preventing patent infringement.
In the Netherlands, limiting a marketing authorisation can be regarded as an (additional) obligation on the generic manufacturer. A generic manufacturer bears a 'best effort obligation' to prevent the use of the patent indication when placing its products on the market, as previously touched upon by the Dutch Supreme Court.
In Novartis/Sun Pharma, where the Supreme Court held that indirect infringement of a Swiss type claim was possible,6 the Supreme Court stated that a generic manufacturer has to substantiate that it has done an effort to prevent that its products are used for the patented indication. The Supreme Court refrained from specifying these obligations.
In that case, Sun Pharma had, amongst other measures, requested the CBG not to include the patented indication on the information on its website. The Supreme Court explicitly stated that a carve-out such as this was not sufficient to fulfil the best effort obligation. The question arises whether the CBG's new policy will have an effect on this principle.
This particular discussion has also taken place in other jurisdictions such as the United Kingdom, where the Supreme Court touched upon the infringement issue and potential intention involved in Warner-Lambert Company v Mylan & Actavis7.
On a side note, the CJEU reminded that after the expiry of the patent, the holder of the marketing authorisation may amend its marketing authorisation as to add the previously patented indication to its indications. In other words, the generic manufacturer may broaden the scope of its marketing authorisation at a later stage.
In summary, this judgment constitutes an interesting development in the recent skinny label discussion. Generally, in order to be on the safe side, generic manufacturers are highly recommended to make use of the possibility of a skinny label.
Furthermore, it is also advisable to adopt other measures concerning the use of the generic product, such as not to include any reference to the patented indication in external communication.