For reference authorisations, Art. 10 of Directive 2001/83/EC governs the protection of the authorisation documents of the previous applicant and generally establishes a 10-year data exclusivity period, with an eight-year exploitation protection period followed by a two-year marketing protection period, which can be extended for an additional year under certain conditions, during which generic drugs may not be marketed. This is the so-called 8+2+1 provision, which is incorporated into Sec. 24b of the German Medicinal Products Act (AMG) in national law. Under Sec. 141 (5) AMG, it does not apply to reference medicinal products if their authorisation was applied for prior to 30 October 2005.
Under Art. 10 (1) in conjunction with (2) of Directive 2001/83/EC, the data exclusivity is initiated by the first authorisation granted under Art. 6 in conjunction with Art. 8 of Directive 2001/83/EC – i.e. by an acquis-compliant authorisation.
In this case, the first authorisation for a medicinal product containing Bendamustin – “Cytostasan” – was granted in 1971. However, it was granted in the former GDR by recordation in that country’s Register of Medicinal Products. After German reunification, the medicinal product was initially deemed to be authorised under the provisions of the EC Legal Transition Regulation (EG-Recht-Überleitungsverordnung) of 18 December 1990 and then went through a retroactive authorisation procedure (Nachzulassungsverfahren), beginning with the filing of a timely application for renewal of the fictitious authorisation on 26 June 1991, by way of analogous application of the procedure in Art. 3 Sec. 7 of the Act Reorganising Medicinal Product Law. By decision dated 19 July 2005, retroactive authorisation was granted for the indications non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). Authorisation was denied for the indiciation chronic lymphatic leukaemia (CLL).
The two ECJ decisions regarding Nivalin, Case C-527/07, dated 18 September 2009, and Memantine, Case C-195/09, dated 28 July 2011, generally established that a positive grant of retroactive authorisation constitutes an acquis-compliant authorisation within the meaning of Art. 6 in conjunction with Art. 8 of Directive 2001/83/EC and therefore initiates the data exclusivity period.
In this regard, it is also relevant that Art. 6 (1) subparagraph 2 of Directive 2001/83/EC provides that data exclusivity begins with the initial authorisation of a substance in the European Union, and all subsequent changes and expansions for the purposes of application of the document provisions are deemed to be components of the same comprehensive authorisation (global marketing authorisation).
The principle of global marketing authorisation conforms to the established case law of the European Court of Justice – ECJ, judgment dated 03 December 1998, Case C-368/96 “Generics”; ECJ, judgment dated 29 April 2004, Case C-106/01, “Novartis” – and must also be followed by national authorities. Under these judgments, no separate protection is granted for new indications.
The global marketing authorisation was implemented in national law in Sec. 25 (9) AMG. However, under Sec. 141 (9) AMG, this does not apply to medicinal products if their authorisation was applied for prior to 06 September 2005. The grant of the initial original authorisation is not controlling with respect to the reference date of 06 September 2005, but rather the granting of the subsequent change or expansion, so that, with respect to the question of the application of Sec. 25 (9) AMG, the focus must be placed on the granting of the subsequent authorisation – Higher Administrative Court (OVG) of Münster, decisions dated 11 October 2013, Case No. 13 B 2756/12, and 27 November 2014, Case No. 13 B 950/14.
II. Facts
On 07 November 2011, Helm AG applied for authorisation to market the medicinal product Alkybend in a decentralised procedure, in which Denmark acted as the reference member state and Finland was one of several concerned member states, in an abridged procedure in accordance with Art. 10 of Directive 2001/83/EC. Ribomustin and Levact, both containing the active ingredient bendamustine, served as the reference medicinal products.
Authorisation for Ribomustin was granted by the Federal Institute for Medicinal Products and Medical Devices for the indications NHL and MM on 19 July 2005 under a retroactive authorisation procedure. Astellas Pharma held the authorisation for Ribomustin.
On 15 July 2010, Astellas received authorisation for Levact under a decentralised procedure, which also contained the active ingredient bendamustine, for the indications NHL, MM as well as for CLL, which had been denied under the retroactive authorisation procedure for Ribomustin. After receiving authorisation for Levact, Astellas waived the authorisation for Ribomustin.
After the conclusion of the DCP procedure, Astellas opposed the generic authorisations that had been granted in both the RMS and all the CMSs, arguing that its data exclusivity period had been infringed, because the granting of the authorisation for Levact in France on 15 July 2010 was controlling with respect to the data exclusivity period in question and not the retroactive authorisation granted in Germany on 19 July 2005.
Astellas asserted this in Germany, the Member State in which the first authorisation for the active ingredient bendamustine was granted on 19 July 2005 (Ribomustin), as well as in the RMS, which coordinated the respective DCP procedure, and in all the CMSs, which participated in the DCP procedure. Gradually, negative decisions were issued in the individual Member States, which all confirmed the lawfulness of the national authorisations granted – with varying degrees of clarity.
III. Questions submitted
The Finnish court submitted two questions to the ECJ for a preliminary ruling.
First, the court wished to know whether Art. 28 (5) and Art. 29 (1) of Directive 2001/83 should be interpreted to mean that the competent authority is authorised to determine the starting date of the data exclusivity period of the reference medicinal product when granting national authorisation.
Second, if the answer is “no”, whether a court may examine the starting date of the data exclusivity period in response to an appeal by the originator, or whether the court is subject to the same restriction as the authority. In addition, the Finnish court wished to know how effective judicial protection can be provided to the originator under Art. 47 of the Charter and Art. 10 of Directive 2001/83 with respect to data exclusivity and whether this includes an obligation for the courts of the individual states to examine whether the initial authorisation to market the reference medicinal product granted in another Member State was issued in conformity with the provisions of Directive 2001/83.
The ECJ answered the first question submitted in the negative and found that the competent national authorities have no authority to decide the starting date of the data exclusivity period. Its rationale was that the decentralised procedure ends when the reference member state determines that all the Member States in which an application for marketing authorisation was filed have reached agreement. Once it has been determined that all the Member States have reached agreement, the competent authorities in the Member States are no longer able to question the results of this procedure when issuing their decisions regarding the marketing of these medicinal products on their sovereign territory. The expiration of the data exclusivity period of the reference medicinal product was examined in this procedure, so that the competent authorities in these Member States cannot make a new examination after agreement has been determined.
With respect to the second question submitted, the ECJ found that the originator must be able to challenge the determination of the starting date of the data exclusivity period in an appeal so as to protect its rights. It follows that, to ensure effective judicial protection, the originator can assert its data exclusivity rights before a court of the Member State whose competent authority made the decision on the authorisation to market the generic drug. However, the originator is not permitted to question this in other Member States.
Accordingly, the ECJ answered the second question by stating that Article 10 of Directive 2001/83 in combination with Article 47 of the Charter are to be interpreted to mean that a court in the affected Member State is authorised to review the determination of the starting date of the data exclusivity period of the reference medicinal product.
However, this court is not authorised to determine whether an initial authorisation to market the reference medicinal product, which was granted in another Member State, was consistent with this Directive.
Based on this pleasing decision of the ECJ, it can be assumed that, in the future, separate complaints contesting the granting of a generic authorisation will no longer be filed in every affected Member State. This will save time and costs and further contribute to harmonisation of the EU’s Single Market in the medicinal product sector.
