CELEX: 62012TJ0472
Medicinal products for human use
Marketing authorisation for the generic medicinal product Zoledronic acid Teva Pharma
zoledronic acid
Regulatory data protection period for the reference medicinal products Zometa and Aclasta, containing the active substance zoledronic acid
Directive 2001/83/EC
Regulation (EEC) No 2309/93 and Regulation (EC) No 726/2004
Global marketing authorisation
Regulatory data protection period

Legal context
Directive 65/65
The legal regime governing the marketing authorisation of medicinal products for human use within the European Union was originally established by Council Directive 65/65/EEC of 26 January 1965 on the approximation of provisions laid down by law, regulation or administrative action relating to proprietary medicinal products (OJ, English Special Edition 1965-1966(I), p. 20) and by Council Regulation (EEC) No 2309/93 of 22 July 1993 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Products (
OJ 1993 L 214, p. 1
). Those measures were subsequently replaced by Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use (
OJ 2001 L 311, p. 67
) and by Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (
OJ 2004 L 136, p. 1
).
Articles 3 and 4 of Directive 65/65, as amended, provide as follows:
‘
Article 3
No medicinal product may be placed on the market of a Member State unless a marketing authorisation has been issued by the competent authorities of that Member State in accordance with this Directive or an authorisation has been granted in accordance with Council Regulation (EEC) No 2309/93 of 22 July 1993 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Products. …
Article 4
For the purpose of obtaining the marketing authorisation provided for in Article 3, the person responsible for marketing shall lodge an application with the competent authority of the Member State.
…
The application shall be accompanied by the following particulars and documents:
…
8.
Results of:
—
physico-chemical, biological or microbiological tests;
—
pharmacological and toxicological tests;
—
clinical trials.
However, and without prejudice to the law relating to the protection of industrial and commercial property:
(a)
The applicant shall not be required to provide the results of pharmacological and toxicological tests or the results of clinical trials if he can demonstrate:
…
(iii)
that the medicinal product is essentially similar to a medicinal product which has been authorised within the Community, in accordance with Community provisions in force, for not less than six years and is marketed in the Member State for which the application is made. … a Member State may also extend this period to 10 years by a single Decision covering all the medicinal products marketed on its territory where it considers this necessary in the interest of public health. …’
Directive 2001/83
Directive 65/65/EC was replaced by Directive 2001/83. Directive 2001/83 was amended, inter alia, by Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001/83 (
OJ 2004 L 136, p. 34
). Article 6(1), Article 8(3)(i) and Article 10(1) and (2) of Directive 2001/83, as amended, are worded as follows:
‘
Article 6
1.   No medicinal product may be placed on the market of a Member State unless a marketing authorisation has been issued by the competent authorities of that Member State in accordance with this Directive or an authorisation has been granted in accordance with Regulation (EC) No 726/2004 …
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).
…
Article 8
…
3.   The application [for marketing authorisation] shall be accompanied by the following particulars and documents …:
…
(i)
Results of:
—
Pharmaceutical (physico-chemical, biological or microbiological) tests;
—
Pre-clinical (toxicological and pharmacological) tests;
—
clinical trials.
…
Article 10
1.   By way of derogation from Article 8(3)(i), and without prejudice to the law relating to the protection of industrial and commercial property, the applicant shall not be required to provide the results of pre-clinical tests and of clinical trials if he can demonstrate that the medicinal product is a generic of a reference medicinal product which is or has been authorised under Article 6 for not less than eight years in a Member State or in the Community.
A generic medicinal product authorised pursuant to this provision shall not be placed on the market until 10 years have elapsed from the initial authorisation of the reference product.
…
The 10-year period referred to in the second subparagraph shall be extended to a maximum of 11 years if, during the first 8 years of those 10 years, the marketing authorisation holder obtains an authorisation for 1 or more new therapeutic indications which, during the scientific evaluation prior to their authorisation, are held to bring a significant clinical benefit in comparison with existing therapies.
2.   For the purposes of this Article:
(a)
“reference medicinal product” shall mean a medicinal product authorised under Article 6, in accordance with the provisions of Article 8;
(b)
“generic medicinal product” shall mean a medicinal product which has the same qualitative and quantitative composition in active substances and the same pharmaceutical form as the reference medicinal product, and whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies. …’
Regulation No 2309/93
Articles 3(1) and (2) and Article 13(4) of and part B of the Annex to Regulation No 2309/93 provided as follows:
‘
Article 3
1.   No medicinal product referred to in Part A of the Annex may be placed on the market within the Community unless a marketing authorisation has been granted by the Community in accordance with the provisions of this Regulation.
2.   The person responsible for placing on the market a medicinal product referred to in Part B of the Annex may request that authorisation to place the medicinal product on the market be granted by the Community in accordance with the provisions of this Regulation.
…
Article 13
…
4.   Medicinal products which have been authorised by the Community in accordance with the provisions of this Regulation shall benefit from the 10-year period of protection referred to in point 8 of the second paragraph of Article 4 of Directive 65/65/EEC.
…
Annex
– …
Part B
—
…
—
Medicinal products administered by means of a new delivery system which, in the opinion of the Agency, constitutes a significant innovation.
—
Medicinal products presented for an entirely new indication which, in the opinion of the Agency, is of significant therapeutic interest.
—
…
—
Medicinal products intended for administration to human being, containing a new active substance which, on the date of entry into force of this Regulation, was not authorised by any Member State for use in a medicinal product intended for human use.
—
…’
Regulation No 726/2004
Regulation No 2309/93 was replaced by Regulation No 726/2004. Article 3(1) and (2), Article 4(1), Article 6(1), Article 14(11), Article 82(1), Article 89 and Article 90 of Regulation No 726/2004 are worded as follows:
‘
Article 3
1.   No medicinal product appearing in the Annex may be placed on the market within the Community unless a marketing authorisation has been granted by the Community in accordance with the provisions of this Regulation.
2.   Any medicinal product not appearing in the Annex may be granted a marketing authorisation by the Community in accordance with the provisions of this Regulation, if:
(a)
the medicinal product contains a new active substance which, on the date of entry into force of this Regulation, was not authorised in the Community; or
(b)
the applicant shows that the medicinal product constitutes a significant therapeutic, scientific or technical innovation or that the granting of authorisation in accordance with this Regulation is in the interests of patients or animal health at Community level.
…
Article 4
1.   Applications for the marketing authorisations referred to in Article 3 shall be submitted to the Agency.
…
Article 6
1.   Each application for the authorisation of a medicinal product for human use shall specifically and completely include the particulars and documents as referred to in [in particular Article 8(3) and Article 10] of … Directive 2001/83/EC. …
Article 14
…
11.   Without prejudice to the law on the protection of industrial and commercial property, medicinal products for human use which have been authorised in accordance with the provisions of this Regulation shall benefit from an 8-year period of data protection and a 10-year period of marketing protection, in which connection the latter period shall be extended to a maximum of 11 years if, during the first 8 years of those 10 years, the marketing authorisation holder obtains an authorisation for 1 or more new therapeutic indications which, during the scientific evaluation prior to their authorisation, are held to bring a significant clinical benefit in comparison with existing therapies.
...
Article 82
1.   Only one authorisation may be granted to an applicant for a specific medicinal product.
However, the Commission shall authorise the same applicant to submit more than one application to the Agency for that medicinal product when there are objective verifiable reasons relating to public health regarding the availability of medicinal products to health-care professionals and/or patients, or for co-marketing reasons.
…
Article 89
The periods of protection provided for in [in particular Article 14(11)] shall not apply to reference medicinal products for which an application for authorisation has been submitted before [20 November 2005].
Article 90
This Regulation shall enter into force on the 20th day following its publication in the
Official Journal of the European Union
.
By way of derogation from the first paragraph, Titles I, II, III and V shall apply from 20 November 2005 …’
Regulation No 1085/2003
Article 1(1), Articles 2, 3 and 6 of and Annex II to Commission Regulation (EC) No 1085/2003 of 3 June 2003 concerning the examination of variations to the terms of a marketing authorisation for medicinal products for human use and veterinary medicinal products falling within the scope of Council Regulation (EEC) No 2309/93 (
OJ 2003 L 159, p. 24
), which has subsequently been replaced by Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products (
OJ 2008 L 334, p. 7
), provided as follows:
‘
Article 1
Subject matter
1.   This Regulation lays down the procedure for the examination of applications for variations to the terms of a marketing authorisation granted in accordance with Regulation (EEC) No 2309/93.
…
Article 2
Scope
This Regulation shall not apply to
(a)
extensions of marketing authorisations which fulfil the conditions set out in Annex II to this Regulation;
…
The extensions referred to in point (a) of the first paragraph shall be evaluated in accordance with [Regulation (EEC) No 2309/93] …
Article 3
Definitions
For the purposes of this Regulation, the following definitions shall apply:
(1)
“variation to the terms of a marketing authorisation” means an amendment to the contents of the documents referred to in [in particular Article 6(1)] of Regulation (EEC) No 2309/93, such as they existed at the moment the decision on the marketing authorisation was adopted …;
(2)
a “ minor variation” of type IA or type IB means a variation listed in Annex I which fulfils the conditions set out therein;
(3)
a “major variation” of type II means a variation that cannot be deemed to be a minor variation or an extension of the marketing authorisation;
…
Article 6
Approval procedure for major variations type II
1.   With regard to major variations of type II, the holder shall submit to the Agency an application …
10.   The Commission shall, where necessary and based on the proposal prepared by the Agency, amend the marketing authorisation that has been granted pursuant to … Regulation (EEC) No 2309/93.
…
Annex II
Changes to a marketing authorisation leading to an extension application as referred to in Article 2
These changes, listed below, will be regarded as an “extension” application as referred to in Article 2.
An extension to or a modification of the existing marketing authorisation will have to be granted by the Community.
The name of the medicinal product will be the same for the “extension” as it is for the existing marketing authorisation of the medicinal product.
…
Changes requiring an extension application
…
2.
Changes to strength, pharmaceutical form and route of administration:
…
(iii)
change or addition of a new strength/potency;
…’
Facts of the dispute
The applicant, Novartis Europharm Ltd (‘Novartis’), is the holder of marketing authorisations for the medicinal products Zometa and Aclasta, both of which contain the active substance zoledronic acid.
Zometa and Aclasta were both authorised in accordance with the centralised procedure, pursuant to Article 4(1) of Regulation No 2309/93.
Zometa was developed by Novartis for the prevention of skeletal complications in patients with advanced malignancies involving bone and for the treatment of tumour-induced hypercalcaemia. Marketing authorisation for Zometa was granted on 20 March 2001.
Zometa is authorised for the following oncology indications: prevention of skeletal-related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumour-induced hypercalcaemia) in patients with advanced malignancies involving bone, as well as for the treatment of tumour-induced hypercalcaemia.
In addition to the Zometa development programme, Novartis initiated various forms of research into the use of zoledronic acid in non-oncology indications, namely the treatment of Paget’s disease of the bone, treatment of osteoporosis in post-menopausal women and in men at increased risk of fracture, including those with a recent low-trauma hip fracture and treatment of osteoporosis associated with long-term systemic glucocorticoid therapy in post-menopausal women and in men at increased risk of fracture. Research into the use of zoledronic acid for those non-oncology indications required a different clinical development programme from that employed for Zometa, with different patient populations and dosing regimens.
The product resulting from that research is Aclasta, which has the same active substance as Zometa, namely zoledronic acid, but which extends the use of that active substance to new, non-oncology, therapeutic indications, with a different strength appropriate to those indications. Marketing authorisation for Aclasta was granted on 15 April 2005.
Aclasta is authorised for the following non-oncology indications:
—
treatment of osteoporosis in post-menopausal women and in men at increased risk of fracture, including those with a recent low-trauma hip fracture;
—
treatment of osteoporosis associated with long-term systemic glucocorticoid therapy in post-menopausal women and in men at increased risk of fracture;
—
treatment of Paget’s disease in adults.
On 25 May 2011, the intervener, Teva Pharma BV (‘Teva’) filed an application for marketing authorisation for the medicinal product Zoledronic acid Teva Pharma — zoledronic acid (‘Zoldedronic acid Teva Pharma’), pursuant to Article 4(1) of Regulation No 726/2004.
Zoledronic acid Teva Pharma is a generic copy of Aclasta. Its active substance is zoledronic acid and its therapeutic indications, which correspond to those of Aclasta, are as follows:
—
treatment of osteoporosis in post-menopausal women and in men at increased risk of fracture;
—
treatment of osteoporosis associated with long-term systemic glucocorticoid therapy in post-menopausal women and in men at increased risk of fracture;
—
treatment of Paget’s disease in adults.
As regards the results of pre-clinical tests and clinical trials, Teva’s application for marketing authorisation referred to the data in the files submitted by Novartis in the procedures for marketing authorisation of Aclasta and Zometa.
On 16 August 2012, the European Commission adopted Implementing Decision C(2012) 5894 final granting a marketing authorisation under Regulation No 726/2004 for the medicinal product for human use Zoledronic acid Teva Pharma (‘the contested decision’). The marketing authorisation granted to Teva is registered in the Community Register of medicinal products under numbers EU/1/772/001 to EU/1/772/004 (Article 1 of the contested decision).
Procedure and forms of order sought by the parties
By application lodged at the Court Registry on 30 October 2012, the applicant brought the present action.
By document lodged at the Court Registry on 24 January 2013, Teva sought leave to intervene in support of the form of order sought by the Commission.
By document lodged at the Court Registry on 5 March 2013, the Commission stated that it had no objections to Teva’s intervention.
By document lodged at the Court Registry on 6 March 2013, the applicant submitted an application for confidential treatment, vis-à-vis Teva, of Annexes A.13 and A.15 to the application and of the two letters attached to Annex A.17. A period was prescribed for Teva to submit its observations.
As Teva did not object to the confidential treatment of those documents within the period prescribed, they were granted confidential treatment in accordance with the Rules of Procedure of the General Court and a non-confidential version of the application prepared by the applicant was communicated to Teva.
By document lodged at the Court Registry on 3 April 2013, the applicant applied for the present case to be joined with Case T‑67/13
Novartis Europharm
v
Commission
.
By document lodged at the Court Registry on 5 April 2013, the applicant stated that it had no objections to Teva’s intervention.
By order of the President of the Eighth Chamber of the General Court of 22 April 2013, Teva was granted leave to intervene in support of the form of order sought by the Commission.
By document lodged at the Court Registry on 24 April 2013, the Commission stated that it had no objections to the joinder of the present case and Case T‑67/13
Novartis Europharm
v
Commission
.
By letter of 28 May 2013, the parties were informed that the President of the Chamber had decided not to grant the application for joinder.
On 12 June 2013, Teva lodged its statement in intervention.
By document lodged at the Court Registry on 9 September 2013, the Commission stated that it had no comments to submit on the statement in intervention.
By document lodged at the Court Registry on 11 September 2013, the applicant submitted its comments on the statement in intervention.
By document lodged at the Court Registry on 12 May 2014, the applicant submitted an application for priority treatment pursuant to Article 55(2) of the Rules of Procedure of the General Court of 2 May 1991.
On 17 October 2014, the Court rejected the application for priority treatment and the parties were informed of this decision by letter of 29 October 2014.
The parties presented oral argument and replied to the Court’s oral questions at the hearing on 13 January 2015.
The applicant claims that the Court should:
—
annul the contested decision;
—
order the Commission to bear its own costs and to pay the applicant’s costs.
The Commission contends that the Court should:
—
dismiss the action;
—
order the applicant to pay the costs.
The intervener contends that the Court should:
—
dismiss the action;
—
order the applicant to pay the costs of the intervention.
Law
In support of its action, the applicant puts forward a single plea for annulment, alleging infringement of Article 10(1) of Directive 2001/83 and Article 13(4) of Regulation No 2309/93, read with Articles 14(11) and 89 of Regulation No 726/2004.
The applicant submits that the decision authorising the placing on the market of Zoledronic acid Teva Pharma is unlawful because it infringes the data protection rights that it enjoys in respect of its medicinal product Aclasta under Article 13(4) of Regulation No 2309/93, in conjunction with Article 14(11) and Article 89 of Regulation No 726/2004. The applicant maintains that Aclasta benefits from a regulatory data protection period of 10 years, which means that Aclasta should not have been used as a reference medicinal product for the purpose of the authorisation of generic products until 15 April 2015.
The Commission, supported by the intervener, contends that the marketing authorisation for Aclasta is included in the global marketing authorisation granted for Zometa in March 2001 and that Aclasta does not enjoy an independent regulatory data protection period. The decision authorising Teva to refer to Aclasta as the reference medicinal product for the marketing of Zoledronic acid Teva Pharma was therefore correct, as the regulatory data protection period applicable to Zometa and Aclasta expired in March 2011.
It should be noted, first, that, under Article 6(1) of Directive 2001/83, as amended, no medicinal product may be placed on the market of a Member State unless a marketing authorisation has been issued by the competent authorities of that Member State in accordance with that directive or an authorisation has been granted in accordance with Regulation No 726/2004. The reference to authorisations granted in accordance with Regulation No 726/2004 is to be understood as a reference to marketing authorisations obtained under the centralised procedure, which was governed, before the entry into force of Regulation No 726/2004, by Regulation No 2309/93, which was applicable when marketing authorisation was granted for Aclasta pursuant to Article 90 of Regulation No 726/2004 (see paragraphs 5 and 8 above).
Pursuant to Article 8(3) of Directive 2001/83 and Article 6 of Regulation No 726/2004, applications for marketing authorisation are to be accompanied by, inter alia, the results of pharmaceutical pre-clinical tests and clinical trials. The purpose of the requirement for applicants seeking marketing authorisation for a medicinal product to attach to their application the results of pharmacological and toxicological tests and clinical trials, laid down in Article 8(3)(i) of Directive 2001/83, is to provide proof of the safety and efficacy of the medicinal product concerned (see judgment of 18 June 2009 in
Generics (UK)
, C‑527/07, ECR,
EU:C:2009:379
, paragraph 22 and the case law cited).
Next, it should be observed that Article 10(1) of Directive 2001/83, as amended, states that an applicant seeking marketing authorisation for a medicinal product is not required to provide the results of pre-clinical tests and clinical trials if he can demonstrate that the medicinal product is a generic of a reference product and the regulatory data protection period for the reference product has expired.
It should be noted in that regard that it is apparent from a reading of Article 13(4) of Regulation No 2309/93 in conjunction with Article 14(11) and Article 89 of Regulation No 726/2004 that the relevant regulatory data protection period for medicinal products authorised in accordance with the centralised procedure before 20 November 2005 is 10 years.
Lastly, it should be pointed out that, under the second subparagraph of Article 6(1) of Directive 2001/83, as amended, when a medicinal product has been granted an initial marketing authorisation in accordance with the first subparagraph, that is in accordance with Directive 2001/83 or under the centralised procedure (see paragraph 40 above), any additional strengths, pharmaceutical forms, administration routes, presentations, as well as any variations and extensions must also be granted marketing authorisation in accordance with the first subparagraph or be included in the initial authorisation and all those marketing authorisations are regarded as belonging to the same global marketing authorisation, in particular for the purposes of the application of Article 10(1) of Directive 2001/83, as amended, that is, for the purpose of the application of the regulatory data protection period.
The notion of a global marketing authorisation referred to in the second subparagraph of Article 6(1) of Directive 2001/83 follows a line of case law established by the Court of Justice to the effect that new therapeutic indications, new doses, administration routes and new pharmaceutical forms of the original medicinal product do not enjoy an independent regulatory data protection period (judgments of 3 December 1998 in
Generics (UK) and Others
, C‑368/96, ECR,
EU:C:1998:583
, paragraphs 43, 44, 53 and 56; 29 April 2004 in
Novartis Pharmaceuticals
, C‑106/01, ECR,
EU:C:2004:245
, paragraphs 57 to 60; and 9 December 2004 in
Approved Prescription Services
, C‑36/03, ECR,
EU:C:2004:781
, paragraphs 25, 26 and 30).
Accordingly, if the marketing authorisation for any additional dosage, pharmaceutical form, route of administration, presentation or any variation or extension of the original medicinal product is included in the global marketing authorisation for that product, the grant of marketing authorisation for such developments does not give rise to an independent regulatory data protection period.
In the present case, the question to be addressed is whether Zometa and Aclasta are covered by the same global marketing authorisation. It should be noted in that connection that it is common ground that the therapeutic indications and strengths for Aclasta are different from those for Zometa. As indicated at paragraph 12 above, Aclasta and Zometa both contain the active substance zoledronic acid and Aclasta was authorised for non-oncology therapeutic indications that were new vis-à-vis the indications for Zometa and for a different strength appropriate for those non-oncology indications. The addition of new therapeutic indications is equivalent to a type II variation under Article 6 of Regulation No 1085/2003, whereas the change to a strength or the addition of a new strength is regarded as an extension under Paragraph 2(iii) of Annex II to Regulation No 1085/2003 (see paragraph 6 above).
On the other hand, it is also common ground that Aclasta was not authorised as a variation to or extension of Zometa within the meaning of Regulation No 1085/2003, but was granted a separate marketing authorisation pursuant to Regulation No 2309/93. Moreover, Aclasta has a different name from Zometa, and both medicinal products have separate entries in the Community Register of medicinal products. The applicant infers from those considerations that the two medicinal products do not form part of the same global marketing authorisation for the purpose of the application of the regulatory data protection period.
In the first place, the applicant submits that the concept of a global marketing authorisation within the meaning of the second subparagraph of Article 6(1) of Directive 2001/83 is confined to variations and extensions authorised in accordance with Regulation No 1085/2003 and, now, with Regulation No 1234/2008, which are included in the terms of the first marketing authorisation granted for the original medicinal product and do not lead to the grant of a new marketing authorisation for a medicinal product with a new name. On the other hand, the concept of a global marketing authorisation does not cover developments authorised by separate marketing authorisations under Regulation No 2309/93 and, now, under Regulation No 726/2004.
The applicant acknowledges that the second subparagraph of Article 6(1) of Directive 2001/83, as amended, refers to developments authorised by means of both a variation of the initial marketing authorisation and the granting of a separate marketing authorisation. According to the applicant, however, that may be explained by the fact that, under the rules laid down by Regulation No 1085/2003, a certain type of variation, namely extensions, had to be assessed in accordance with the authorisation procedures laid down by Regulation No 2309/93, as provided for in Article 2 of Regulation No 1085/2003 (see paragraph 6 above), rather than in accordance with the accelerated variations procedure.
It should be noted that, in accordance with settled case-law, it is necessary, in interpreting a provision of EU law, to consider not only its wording but also the context in which it occurs and the objectives pursued by the rules of which it is part (see judgments of 7 June 2005 in
VEMW and Others
, C‑17/03, ECR,
EU:C:2005:362
, paragraph 41 and the case-law cited, and 26 October 2010 in
Germany
v
Commission
, T‑236/07, ECR,
EU:T:2010:451
, paragraph 44 and the case-law cited).
First, it is clear that the wording of the second subparagraph of Article 6(1) of Directive 2001/83, as amended, does not make any distinction between a development of the original medicinal product authorised through an amendment of the terms of the initial marketing authorisation and a development of the original medicinal product authorised through the grant of a separate marketing authorisation and name; in both cases, the original medicinal product and any additional strengths, pharmaceutical forms, administration routes, presentations, as well as any variations and extensions, irrespective of whether they were authorised by the grant of a separate marketing authorisation and name or by being included in the terms of the initial marketing authorisation, form part of the same global marketing authorisation for the purpose of the application of the regulatory data protection period. The global marketing authorisation is therefore given a substantive rather than a formal definition, which means that a global marketing authorisation thus construed may encompass, formally, a number of separate marketing authorisations.
The explanation proposed by the applicant, as summarised in paragraph 50 above, that the second subparagraph of Article 6(1) of Directive 2001/83, as amended, refers not only to developments authorised by means of a variation of an initial marketing authorisation but also those authorised by the grant of a separate marketing authorisation, because, under the rules laid down by Regulation No 1085/2003, an extension application had to be assessed in accordance with Regulation No 2309/93 and, after the repeal of that regulation, with Regulation No 726/2004 (see paragraph 6 above), cannot be accepted. Even though such extensions had to be authorised in accordance with the procedure laid down by Regulations No 2309/93 and No 726/2004, they led, by virtue of Annex II to Regulation No 1085/2003, to an amendment of the initial marketing authorisation, not to the grant of a separate marketing authorisation and a separate name (see paragraph 6 above).
Second, having regard to the context in which the second subparagraph of Article 6(1) of Directive 2001/83 was adopted, it should be noted that none of the provisions of Directive 2001/83, Regulation No 2309/93 and, now, Regulation No 726/2004, or Regulations No 1085/2003 and No 1234/2008 on variations and extensions specifically determine the cases in which a development of a medicinal product should be authorised by means of a variation of the terms of the initial marketing authorisation or the cases in which such a development should be authorised by the grant of a separate marketing authorisation.
As confirmed by the intervener at the hearing, under the rules laid down by Regulation No 2309/93, there was nothing to prevent several separate marketing authorisations being granted in respect of a single medicinal product, restrictions in that regard having been introduced, as the applicant itself acknowledges, only as a result of Article 82(1) of Regulation No 726/2004.
Therefore, at the time the marketing authorisation was granted for Aclasta, given that (as indicated in paragraphs 12 and 47 above), Aclasta and Zometa both contain the active substance zoledronic acid and differ from each other only as regards their therapeutic indications and strengths, which corresponds to a type II variation and an extension within the meaning of Regulation No 1085/2003 (see paragraph 6 above), Novartis was entitled, if it so chose, to submit an application for a type II variation and extension in accordance with that regulation in order to obtain a variation of the terms of the marketing authorisation for Zometa, or, if it preferred, to submit an application for a separate marketing authorisation for the modified medicinal product with a new trade name. The applicant confirmed at the hearing that, in order to obtain the marketing authorisation for Aclasta, it could have submitted an application to vary the terms of the marketing authorisation for Zometa, formal note of which was taken in the minutes of the hearing.
As regards the choice between submitting such an application to vary the terms of the initial marketing authorisation and submitting an application for a separate marketing authorisation, the applicant expressly indicated in a letter to the European Medicines Agency (EMA) on 26 February 2001 that it intended to pursue the option of applying for a separate marketing authorisation and a new trade name for the non-oncology indications for zoledronic acid because ‘the posology, expected safety profile, target prescribers, etc. [for the non-oncology indications] would be different from those in the oncology settings’ and because it wished to ‘differentiate the use of the product in these two settings, especially to avoid misinterpretations of the PIL information by patients’.
Similarly, the European Public Assessment Report (EPAR) for Aclasta, cited by the Commission, states as follows:
‘The Applicant [,] Novartis Europharm Ltd [,] submitted a complete stand-alone application for Marketing Authorisation for Aclasta for the proposed indication of “Treatment of Paget’s disease of the bone”. The active substance of Aclasta, zoledronic acid (zoledronate) … has been previously approved within the EU as Zometa (EMEA/H/C/336) for the treatment of malignancy-induced hypercalcaemia and prevention of skeletal-related events in patients with advanced malignancies involving bone. In the oncology indications, zoledronic acid is given repeatedly as an intravenous infusion of 4 mg over at least 15 minutes every 3-4 weeks. For Paget’s disease, on the other hand, zoledronic acid is proposed to be given as a single intravenous infusion of 5 mg to induce a long-lasting biochemical remission. The Applicant uses a separate invented name and label for the benign indication to avoid any potential confusion between the different doses and dosing interval compared with the oncology indications.’
It follows from the foregoing that the submission of an application for a separate marketing authorisation and a new name for Aclasta rather than the submission of an application for variation and extension of the marketing authorisation for Zometa was a commercial decision on the part of Novartis. As Advocate General Jacobs observed in his Opinion in
Novartis Pharmaceuticals
(C‑106/01, ECR,
EU:C:2003:49
, point 57), the market strategy of an undertaking cannot affect the application of the regulatory period of data protection of one and the same active substance because ‘[t]o exclude the application of the [judgment in
Generics (UK) and Others
(cited in paragraph 45 above,
EU:C:1998:583
)] 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 approach advocated by the applicant whereby an independent regulatory data protection period automatically starts to run as a result of a variation authorised by the grant of a separate marketing authorisation would have the effect of giving applicants a new regulatory data protection period whenever they improved the original product, applied for marketing authorisation for the improved version of the product and such authorisation was granted, with the result that the regulatory date protection period would automatically be extended indefinitely for one and the same reference medicinal product.
Third, it should be noted in that regard that such an approach is 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.
Article 10(1) of Directive 2001/83 — which provides for the possibility of derogating from the requirement laid down in Article 8(3)(i) of that directive to provide the results of pharmaceutical pre-clinical tests and clinical trials for the purpose of obtaining marketing authorisation for a medicinal product, if the applicant can demonstrate that the medicinal product that is the subject of the application is a generic of a reference medicinal product which has been authorised within the European Union and the regulatory data protection period has expired — seeks to reconcile, on the one hand, the provision of adequate protection for the research and development work undertaken by innovative pharmaceutical companies and, on the other, the wish to avoid excessive testing on humans and animals. Thus, according to recital 9 in the preamble to Directive 2001/83, ‘it is advisable to stipulate more precisely the cases in which the results of toxicological and pharmacological tests or clinical trials do not have to be provided with a view to obtaining authorisation for a medicinal product which is essentially similar to an authorised product, while ensuring that innovative firms are not placed at a disadvantage’, whereas recital 10 states that ‘there are reasons of public policy for not conducting repetitive tests on humans or animals without over-riding cause’.
Moreover, the notion of a global marketing authorisation referred to in the second subparagraph of Article 6(1) of Directive 2001/83, as amended, follows the line of well-established case-law of the Court of Justice (see paragraph 45 above), which developed that notion in particular to take account of the objective of the ‘abridged’ procedure, which is to save the time and expense needed to gather the results of the pharmacological and toxicological tests and clinical trials, and to avoid the repetition of tests on humans or animals (see judgment of 16 October 2003 in
AstraZeneca
, C‑223/01, ECR,
EU:C:2003:546
, paragraph 52). That objective would clearly be jeopardised if the producer of the original medicinal product were able to extend indefinitely the regulatory period of data protection and thus prevent producers of generic medicinal products from using that product as a reference product when the regulatory data protection period expressly provided for by the legislature in order to reconcile the interests of innovative undertakings and the general interest expired.
As regards the argument that innovations to improve or develop the original medicinal product may require further investment, the Court of Justice expressly stated in
Generics (UK) and Others
, cited in paragraph 45 above (
EU:C:1998:583
, paragraph 52), that it is, where appropriate, for the EU legislature to adopt measures to reinforce the rules for the protection of innovating undertakings.
Thus, Article 10 of Directive 2001/83 was amended by Directive 2004/27 and Article 14(11) of Regulation No 726/2004 was introduced to provide an additional year of protection in the event of significant innovation during the first 8-year period after the marketing authorisation was granted. Now, the regulatory data protection period is extended to a maximum of 11 years if, during the first 8 years of the regulatory 10-year data protection period, the marketing authorisation holder obtains an authorisation for 1 or more new therapeutic indications which, during the scientific evaluation prior to their authorisation, are considered to bring a significant clinical benefit in comparison with existing therapies.
Accordingly, the applicant’s position is also at variance with developments in legislation after marketing authorisation was granted for Aclasta, in particular the introduction of the possibility to extend by 1 year the regulatory period of data protection of a medicinal product in the event of significant innovation during the first 8 years after the authorisation was granted (see paragraph 65 above), in order to ensure a return on investment in new studies conducted for such innovation. The possibility of securing a 1-year extension would be pointless if, by obtaining a separate marketing authorisation for new therapeutic indications and a new strength, applicants were able to obtain automatically a new regulatory 10-year period of data protection with effect from the date on which the separate authorisation was granted.
It follows from the foregoing considerations that, in the November 2005 edition of the document entitled ‘Notice to Applicants’, the Commission was correct to point out, in paragraphs 2.3 and 6.1.4 of Chapter 1 in Volume 2A of that document, which, while not legally binding, may provide a helpful reference point for a judicial assessment (Opinion of Advocate General Wahl in
Olainfarm
, C‑104/13, ECR,
EU:C:2014:342
, point 39), that ‘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 and under a different name, granted to the marketing authorisation holder of the initial authorisation …’ and that ‘for a reference medicinal product, the start of the data and market exclusivity periods is the date when the first marketing authorisation was granted in the Community’. Those provisions also state that ‘[a]ll additional strengths, pharmaceutical forms, administration routes, presentations as well as any variation and extensions have the same end point of the data and market exclusivity periods, namely 8 and 10 years after the first marketing authorisation was granted, respectively’ and, lastly, that ‘[t]his will apply even if the new presentation has been authorised to the same marketing authorisation holder through a separate procedure and under a different name’. That statement is equally valid as regards the regulatory 10-year data protection period applicable to medicinal products authorised under the centralised procedure before 20 November 2005 (see paragraph 43 above).
In the second place, the applicant none the less maintains that the application of regulatory data protection rights to medicinal products differs according to whether the medicinal products in question are authorised in accordance with national procedures or the centralised procedure pursuant to Regulation No 2309/93 and, now, Regulation No 726/2004. According to the applicant, the specific purpose of selective access to the centralised procedure is to enable medicinal products regarded as innovative or of significant therapeutic interest to enjoy a further regulatory period of data protection, even if the medicinal product in question is a new variant of a product authorised previously.
Accordingly, the applicant contends that if a producer is authorised, on the basis of the criteria governing access to the centralised procedure, to submit an application for a new marketing authorisation for a new medicinal product with a new name under the centralised procedure, his product will have the benefit of a new global marketing authorisation and, therefore, a new regulatory data protection period. It is therefore possible under existing legislation to apply for and obtain more than one global marketing authorisation for medicinal products containing the same active substance if the application for the new marketing authorisation meets the specific access criteria relating to innovation governing the centralised procedure.
In the applicant’s submission, the consequences of the different authorisation regimes under Directive 2001/83 and Regulations No 2309/93 and No 726/2004 are as follows: in the context of the (national) authorisation procedures under Directive 2001/83, the holder of a marketing authorisation can obtain only one marketing authorisation for a medicinal product with a specific active substance, covering the first marketing authorisation and all product variants based on the same active substance, which must be authorised as variations or extensions. Under Article 6(1) of the directive, all those authorisations form part of a single, global marketing authorisation for a medicinal product with a single name having one and the same data protection period.
Under the centralised procedure introduced by Regulations No 2309/93 and No 726/2004, the holder of a marketing authorisation has, according to the applicant, the option to apply for a new marketing authorisation for another product containing the same active substance for which access to the centralised procedure has been granted on the basis of innovation-specific access criteria. This new marketing authorisation does not fall within the categories of authorisation described in Article 6(1) of Directive 2001/83 and must therefore be regarded as a separate global marketing authorisation, triggering its own regulatory data protection period.
This argument cannot succeed.
First, as observed by Advocate General Sharpston in her Opinion in
Commission
v
Lithuania
(C‑350/08, ECR,
EU:C:2010:214
, points 90 to 92) and
Novartis Pharma
(C‑535/11, ECR,
EU:C:2013:53
, point 47), the rules laid down in Regulations No 2309/93 and No 726/2004, in Directive 2001/83 and, previously, in Directive 65/65, cannot be read in isolation from one another and must be read together.
Whereas the rules laid down in the regulations contain a number of provisions that are essentially procedural (see Article 1 of Regulation No 726/2004), the rules laid down in the directive essentially contain substantive provisions regarding the standards to be observed to uphold product quality and protect human health. Therefore, irrespective of the procedure, medicinal products must satisfy the same substantive requirements and may claim the same protection.
Thus, the sixth recital in the preamble to Regulation No 2309/93 stated expressly that ‘the same criteria [as those applicable to products authorised at national level] must be applied to medicinal products which are to be authorised by the Community’, and Article 13(4) of that regulation provided that medicinal products which had been authorised by the Community in accordance with that regulation were to benefit from the period of data protection referred to in Directive 65/65. Similarly, recital 11 in the preamble to and Article 14(11) of Regulation No 726/2004 expressly provide that the regulatory data protection period under the centralised procedure is exactly the same as that provided for in Directive 2001/83.
The conclusion that the directive and the regulations form a uniform, harmonised set of rules in so far as concerns the substantive law applicable to the authorisation of medicinal products is further supported by the fact that the legislature introduced at the same time, that is on 31 March 2004 (see paragraphs 3 and 5 above), the amendments made to Directive 2001/83 by Directive 2004/27 and Regulation No 726/2004.
Next, it should be noted, first, that the interpretation proposed by the applicant is at odds with the principles established by Regulation No 726/2004. Thus, while, under the rules laid down by Regulation No 2309/93, there were no restrictions as to the number of marketing authorisation applications an applicant could make in respect of a single medicinal product, Article 82(1) of Regulation No 726/2004 now provides that, unless there are objective verifiable reasons relating, in particular, to public health, an applicant can make only one marketing authorisation application for a specific medicinal product under the centralised procedure, whereas Directive 2001/83 imposed no such restrictions for national authorisation procedures.
It should be noted, second, that the applicant also maintains that the claim that, under the regulations at issue, medicinal products the marketing of which has been authorised in accordance with the centralised procedure benefit from an independent data protection period is supported by the fact that the verb ‘shall benefit from’, as used in Article 13(4) of Regulation No 2309/93 and in Article 14(11) of Regulation No 726/2004, is in the imperative voice and thus provides the applicant with the certainty that, if his application is eligible for assessment under the centralised procedure and is authorised in accordance with that procedure, he will benefit from a 10-year period of data protection. On the other hand, Directive 2001/83 contains no specific provision granting data protection to a medicinal product or protection for data provided with a view to obtaining marketing authorisation for that product, and data protection can be enforced only in the case of a generic application for marketing authorisation within the meaning of Article 10(1) of the directive.
That argument must be rejected. As the intervener was correct to observe, not only is the purpose of Article 10(1) of Directive 2001/83 specifically to regulate the periods of data protection from which medicinal products are to benefit, so that it cannot be claimed that the directive contains no provision on the data protection of medicinal products, but also the wording of that article, which states that a generic medicinal product ‘shall not be placed on the market’ until 10 years have elapsed from the grant of the initial marketing authorisation of the reference product, is expressed in exactly the same unconditional terms as the provisions of Regulations No 2309/93 and No 726/2004 invoked by the applicant.
It follows from the foregoing that the applicant’s argument by which it seeks to demonstrate that the application of regulatory data protection rights to medicinal products differs according to whether the products are authorised in accordance with national procedures or with the centralised procedure under Regulation No 2309/93 and, now, under Regulation No 726/2004, must be rejected. Contrary to what is claimed by the applicant, the purpose of the eligibility criteria for the centralised procedure is not to enable innovative medicinal products to benefit from a new regulatory period of data protection, even where the product in question is a new variant of a medicinal product authorised previously, the purpose of those criteria being simply to govern access to the centralised procedure.
It is apparent from the above that the applicant’s argument that the case-law of the Court of Justice, in particular that originating from
Novartis Pharmaceuticals
, cited in paragraph 45 above (
EU:C:2004:245
), is irrelevant in the present case as that judgment concerns medicinal products authorised at national level, not products authorised in accordance with the centralised procedure, such as those at issue in the present case, must also be rejected. Neither Article 6(1) of Directive 2001/83, as amended, nor the case law originating from
Novartis Pharmaceuticals
, cited in paragraph 45 above (
EU:C:2004:245
), makes any distinction on the basis of whether the procedure followed to obtain marketing authorisation was a national or centralised procedure.
It follows from all the foregoing considerations that the scope of a global marketing authorisation, as defined in the second subparagraph of Article 6(1) of Directive 2001/83, as amended, encompasses developments for which separate marketing authorisations have been granted under the centralised procedure. The fact that Novartis was able to obtain, by means of that procedure, a marketing authorisation for new therapeutic indications with a new name, namely Aclasta, is therefore irrelevant for the purpose of the application of the regulatory data protection period.
Accordingly, as the intervener and the Commission were correct to observe, there is absolutely no need for the Court to rule on the question — which was the subject of discussion between the parties — whether the marketing authorisation granted for Aclasta under the centralised procedure was based on ‘innovation-specific criteria’, as laid down at the material time in Part B of the Annex to Regulation No 2309/93, or whether Novartis was entitled to submit a new marketing authorisation application in accordance with the centralised procedure in order to obtain marketing authorisation for Aclasta because that product contained a new active substance which was not authorised in the European Union before 1995.
That question would be relevant only if the conditions for obtaining a marketing authorisation in accordance with the centralised procedure were of any relevance to the issue whether a new therapeutic indication could benefit from a new regulatory data protection period, which is not the case, as is apparent from the considerations set out in paragraphs 68 to 80 above.
As a consequence, as the Commission was right to point out, even though Novartis was entitled to submit an application for marketing authorisation using the centralised procedure for Aclasta, because it satisfied the innovation-specific criteria laid down in Part B of the Annex to Regulation No 2309/93 for application of the centralised procedure, Aclasta could not be granted an independent global marketing authorisation or a new regulatory data protection period.
It follows that the applicant’s argument based on its claim that it was entitled to submit a marketing authorisation application for Aclasta under the centralised procedure on the basis of innovation-specific criteria governing access to that procedure is ineffective.
It follows from all the foregoing considerations that the situation under consideration in the present case is precisely the type of situation referred to in the second subparagraph of Article 6(1) of Directive 2001/83, as amended, as Aclasta constitutes an additional strength and a variation, consisting in new therapeutic indications, by comparison with Zometa, and must therefore be included in the global marketing authorisation for Zometa. It follows that Zometa and Aclasta are covered by the same global marketing authorisation for the purposes of the regulatory data protection period and that, accordingly, the Commission was entitled to permit Teva to refer to the data in the files relating to the marketing authorisation of Zometa and Aclasta in the application for marketing authorisation for Zoledronic acid Teva Pharma.
The action must therefore be dismissed.
Costs
Under Article 134(1) of the Rules of Procedure of the General Court, the unsuccessful party is to be ordered to pay the costs if they have been applied for in the successful party’s pleadings. Since the applicant has been unsuccessful, and the Commission and the intervener have applied for costs, the applicant must be ordered to pay the costs.

On those grounds,
THE GENERAL COURT (Second Chamber)
hereby:

1.
Dismisses the action;

2.
Orders Novartis Europharm Ltd to bear its own costs and to pay the costs incurred by the European Commission and by Teva Pharma BV.

Martins Ribeiro
Gervasoni
Madise
Delivered in open court in Luxembourg on 15 September 2015.
[Signatures]
(
*1
)	Language of the case: English.