Pregabalin - Netherlands

On Oct 04, 2018, Advocate General Kokott at the Court of Justice of the European Union issued opinion on label carve-out issue filed by Warner-Lambert Company.

Background: Warner-Lambert markets worldwide the medicinal product Lyrica®, with the active substance pregabalin, for the indications epilepsy, generalised anxiety disorder and neuropathic pain. Warner-Lambert is the holder of the European Patent EP 0 934 061 (expired in 2017) which claims neuropathic pain. After the data exclusivity period for the medicine Lyrica had expired in 2015, several manufacturers of generic medicinal products, including Aurobindo, applied to the Medicine Evaluation Board (CBG) under the decentralised procedure for a marketing authorisation for a generic medicinal product. The original application by Aurobindo in the decentralised authorisation procedure did not contain a carve-out for the indication neuropathic pain, but a full label version of the summary of product characteristics, which also included the still patented indication. After the marketing authorisation had been granted, but before its generic pregabalin-based medicinal product had been placed on the market, Aurobindo notified the CBG that it would subsequently introduce a carve-out, that is, in the case at hand, delete from the summary of product characteristics the still patented indication neuropathic pain. Aurobindo requested the CBG to publish the summary in accordance with the subsequent carve-out. The CBG did not comply with that request, however, but published the full label version of the summary. Thereupon, Warner-Lambert made an application for interim measures at the Hague District Court, claiming that the Netherlands State should be ordered to instruct the CBG to replace the published full label version of the summary of product characteristics with the carve-out version. The court hearing the application for interim measures allowed Warner-Lambert’s claims in part. In the appeal proceedings before the Court of Appeal, the Netherlands State is now requesting that the judgment of the Hague District Court be set aside. By order of 4 July 2017 the Court of Appeal made a reference to the CJEU.

Questions: The question was basically, whether carved out summary of product characteristics of generic referring to indications or dosage forms covered by the patent of a third party should be considered as a request to limit the marketing authorisation for that generic medicinal product & whether it must be interpreted as precluding the competent authority from making public the whole summary of characteristics and the package leaflet of a medicinal product, in a situation where the marketing authorisation applicant or holder has sought approval for non-patented indication only.   

Opinion: Advocate General Kokott in her opinion stated that the marketed version of a medicinal product must be the same as the authorised version. This is not only essential in order to guarantee legal certainty and transparency, but it is also consistent with the spirit and purpose of the carve-out arrangement in the second sentence of Article 11 of Directive 2001/83. Not only the initial introduction of a carve-out at the time of submitting marketing authorization application but also the subsequent introduction of a carve-out must therefore result in the limitation of the marketing authorisation for a medicinal product. The carve-out arrangement in the second sentence of Article 11 of Directive 2001/83, whereby still patented indications or dosage forms of the reference medicinal product need not be included in the summary of characteristics of a generic medicinal product, permits an exception to the principle of the uniformity of the reference medicinal product and the generic medicinal product. This is necessary so that generic medicinal products can be placed on the market after the data exclusivity period for reference medicinal products has expired, even if individual indications or dosage forms of the reference medicinal product are still patented. The wording of the second sentence of Article 11 of Directive 2001/83 is unclear in respect of whether a carve-out can also be introduced after the marketing authorisation has been granted for a medicinal product. However, the subsequent carve-out proves to be essential in any case in the complex system of authorisation of medicinal products under Directive 2001/83. Even though patent protection differs in the various Member States, the directive nevertheless provides for parallel application for a marketing authorisation for a medicinal product in all or several Member States or application for recognition of a marketing authorisation granted in one Member State in other Member States. Against this background, it seems logical to interpret the second sentence of Article 11 of Directive 2001/83 to the effect that it is also possible to introduce a carve-out after the marketing authorisation has been granted for a medicinal product. In order to ensure that the authorised version of a medicinal product corresponds to the version placed on the market, a subsequent carve-out of this nature must be regarded as an application to limit the marketing authorisation.

With respect to second question, the referring court wants to know whether the competent authorities may publish a full label version of the summary of product characteristics even though a carve-out has been notified. The third question seeks to ascertain whether it makes any difference that the authority requires the authorisation holder to refer in the package leaflet for the medicinal product, which does not contain the indication affected by the carve-out, to the authority’s website, on which the full label version of the summary of product characteristics can be found. The answer to the second and third questions follows from the proposed answer to the first question since, under Article 21(3) of Directive 2001/83, the competent authorities must make publicly available the summary of the product characteristics for each medicinal product which they have authorised. Accordingly, Article 11 and Article 21(3) of Directive 2001/83 must be interpreted as precluding the competent authority from making public the summary of characteristics and the package leaflet of a medicinal product, including those parts referring to indications or dosage forms which are covered by patent law, in a situation where the marketing authorisation applicant or holder has notified the authority that, in accordance with the second sentence of Article 11 of the directive, he is not including such indications or dosage forms in the summary of characteristics and the package leaflet.  

In light of the foregoing, Advocate General Kokott proposed that the Court answer the request for a preliminary ruling from the Gerechtshof the Haag (Court of Appeal, The Hague, Netherlands) as follows:

1.      Articles 10 and 11 of Directive 2001/83/EC on the Community code relating to medicinal products for human use, as amended by Directive 2012/26/EU, must be interpreted as meaning that a communication whereby the marketing authorisation applicant or holder for a generic medicine, within the meaning of Article 10, notifies the authority that he is not including in the summary of product characteristics and the package leaflet, pursuant to the second sentence of Article 11, those parts of the summary of product characteristics for the reference medicine referring to indications or dosage forms covered by the patent right of a third party should be considered as a request to limit the marketing authorisation for that generic medicinal product to the remaining indications or dosage forms.

2.      Article 11 and Article 21(3) of Directive 2001/83 must be interpreted as precluding the competent authority from making public the summary of characteristics and the package leaflet of a medicinal product, including those parts referring to indications or dosage forms which are covered by patent law, in a situation where the marketing authorisation applicant or holder has notified the authority that, in accordance with the second sentence of Article 11 of the directive, he is not including such indications or dosage forms in the summary of characteristics and the package leaflet.