Last updated: 21 December 2023
See updates at the end of the post.
The parties involved in the case
The parties involved in this case were Pharmaceutical Works Polpharma S.A versus the European Medicines Agency (Case T-611/18) supported by the European Commission and Biogen Netherlands BV.
The case and its outcome in brief
- In June 2018, the company, Pharmaceutical Works Polpharma S.A (Poland) submitted an application to the EMA for marketing authorisation for a generic medicinal product derived from the product Tecfidera (containing the API Dimethyl Fumarate), the MA holder for which is Biogen Netherlands BV.
- In July 2018, the EMA concluded that it was unable to validate the applicant’s application for the grant of a marketing authorisation. (More detail is provided in the table Timeline of Events)
- In October 2018 Pharmaceutical Works Polpharma S.A brought an action against the EMA
- On 5 May 2021, the general court delivered its judgement (Case T-611/18) (more information below under the heading The proceedings and the judgement of the general court) in which it declared invalid, the decision of the European Medicines Agency (EMA) of 30 July 2018 not to validate the application submitted by Pharmaceutical Works Polpharma S.A. with a view to obtaining a marketing authorisation for a generic version of the medicinal product Tecfidera
- Pharmaceutical Works Polpharma S.A has since applied to the EMA for a marketing authorisation for a generic medicinal product. A marketing authorisation valid throughout the EU for the generic product Dimethyl fumarate Polpharma was granted on 13 May 2022.
- On 14 and 15 July 2021, three appeals were brought which sought to have set aside the judgment of the General Court of the European Union of 5 May 2021 (more information below under the heading Appeals to the judgement of the general court).
- On 6 October 2022, the advocate general delivered an opinion on the appeals (more information below under the heading Opinion of the advocate general on the appeals).
- On 16 March 2023, The Court of Justice set aside the judgment of the General Court of the European Union of 5 May 2021 and dismissed the action brought by Pharmaceutical Works Polpharma S.A. in Case T‑611/18 (More information below under the heading Outcome of the appeals (judgement)) .
- On 19 December 2023, Biogen said that the the European Commission has revoked the centrally authorised marketing authorizations for generic versions of its multiple sclerosis drug Tecfidera held by the firms Accord, Neuraxpharm, Polpharma and Teva.
The proceedings and the judgement of the general court
Here you can read the brief version of the judgement.
Here, you can read the full version of the judgement (which includes the background to the case), from which the timeline tabulated below was prepared. This should hopefully facilitate a better understanding of some of the finer points of the judgement and in the process help to develop a better/deeper understanding of specific Articles of Directive 2001/83/EC or Regulation (EC) No 726/2004 insofar as a global marketing authorisation, data and market exclusivity, and the definition of a ‘generic’ medicine (Article 10(1) Directive 2001/83) are concerned. The notion of a ‘global marketing authorisation’ is also defined in section 2.3 of Volume 2A Procedures for marketing authorisation CHAPTER 1 MARKETING AUTHORISATION of the Notice to Applicants.
Here you can read an abbreviated version of the proceedings of the case.
Appeals to the judgement of the general court
Three appeals under Article 56 of the Statute of the Court of Justice of the European Union (CJEU), were brought on 14 July 2021 (C‑438/21 P and C‑439/21 P) and 15 July 2021 (C‑440/21 P).
By their respective appeals:
- the European Commission ( P),
- Biogen Netherlands BV (‘Biogen’) (C‑439/21 P) and
- the European Medicines Agency (EMA) (C‑440/21 P)
seek to have set aside the judgment of the General Court of the European Union of 5 May 2021, Pharmaceutical Works Polpharma v EMA (T‑611/18, EU:T:2021:241; ‘the judgment under appeal’), by which the General Court annulled the EMA’s decision of 30 July 2018 not to validate the application submitted by Pharmaceutical Works Polpharma S.A. (‘Polpharma’) with a view to obtaining a marketing authorisation for a generic version of the medicinal product Tecfidera (‘the decision at issue’).
Opinion of the advocate general on the appeals
On 6 October 2022, the advocate general delivered an opinion on the appeals, with the following conclusion:
In the light of the foregoing, I suggest that the Court:
- set aside the judgment of the General Court of the European Union (Seventh Chamber, Extended Composition) of 5 May 2021, Pharmaceutical Works Polpharma v EMA (T‑611/18, EU:T:2021:241);
- dismiss the action for annulment brought by Pharmaceutical Works Polpharma S.A. at first instance;
- order Pharmaceutical Works Polpharma S.A. to pay the costs.
Outcome of the appeals (judgement)
On 16 March 2023, The Court of Justice:
1. Set aside the judgment of the General Court of the European Union of 5 May 2021, Pharmaceutical Works Polpharma v EMA (T‑611/18, EU:T:2021:241);
2. Dismissed the action brought by Pharmaceutical Works Polpharma S.A. in Case T‑611/18;
3. Ordered Pharmaceutical Works Polpharma S.A. to bear its own costs and to pay those incurred by the European Commission, Biogen Netherlands BV and the European Medicines Agency (EMA).
You can read the full judgement of the case here.
Comments concerning this case in the minutes of CMDh meetings
1) CMDh meeting of 17-19 May 2022
In section 4.2 on pages 10-11 of the meeting minutes of the above meeting, it states:
The CMDh was informed that the EC decision on the extension of indication application for Tecfidera was finalised and published with a note referring to the judgment of the General Court in case T-611/18, which is currently under appeal. Based on the ad-hoc CHMP assessment, that concluded that it cannot be established that monoethyl fumarate salts (MEF) exerts a clinically relevant therapeutic contribution within Fumaderm and the Judgment of the General Court of 5 May 2021 in Case T-611/18 it was determined that Tecfidera does not benefit from an independent global marketing authorisation and thus an additional year of marketing protection in accordance with Article 14(11) of Regulation (EC) No 726/2004 was not granted. EC decisions on three generics MAs submitted through the centralised procedure have also been finalised and published.
A letter from the MAH of Tecfidera (Biogen), outlining their legal arguments, was shared with MSs for information to take into account in the ongoing generic applications. It was noted that generic applicants need to justify in their applications why they consider that Tecfidera and Fumaderm belong to the same GMA.
2) CMDh meeting of 28 – 30 March 2023
In section 4.1 on page 13 of the meeting minutes of the above meeting, there are the following comments on the outcome of the appeals
The CMDh discussed the implications of the CJEU judgment in the joined cases C-438/21 P, C-439/21 P, C-440/21 P on generic marketing authorisations containing dimethyl fumarate. Letters from the EC, the MAH of the originator (Tecfidera) and from several generic MAHs were noted.
The EC informed the CMDh that the ECJ judgment sets aside the judgment of the General Court of the European Union of 5 May 2021, Pharmaceutical Works Polpharma v EMA (T611/18) and thus, confirms the rights to regulatory data protection for the reference medicinal product, including the market protection period which is still ongoing.
The EC also informed the CMDh members of the regulatory actions envisaged both for the generic marketing authorisations and the Tecfidera Decision, and their foreseen timelines.
The CMDh noted that it would be a national decision by each MSs which actions to take for nationally authorised generics.
There was also a discussion if for generics that were submitted with Fumaderm as RefMP for the purpose of data exclusivity, following the previous judgement (under the assumption at the time that Fumaderm and Tecfidera belong to the same GMA), a switch of the RefMP would be possible in this specific case. Some MSs considered that a switch of the RefMP should be possible in this specific case without setting a precedence for future cases. Others were not in favour of allowing a switch in line with the usual handling of RefMPs.
MSs were asked to keep each other informed about regulatory actions taken at national level and the grounds thereof and whether they would allow a switch of the RefMP in this specific case.
3) CMDh meeting of 24-25 April 2023
In section 4.3 on page 11 of the meeting minutes of the above meeting, it states:
Following the discussion in March 2023, where it was concluded that after the CJEU judgment in the joined cases C-438/21 P, C-439/21 P, C-440/21 P on generic marketing authorisations containing dimethyl fumarate, it would be a national decision by each MSs which actions to take for nationally authorised generics, the CMDh discussed again if for some actions a harmonised EU approach could be agreed.
Further discussions on the judgement are expected in May. MSs were asked to share the outcome of their discussions at national level once available
The EC updated the CMDh on the regulatory actions initiated and the timelines for both for the centrally authorised DMF generic marketing authorisations and the Tecfidera decision on the extension of the marketing protection of one additional year in accordance with Article 14(11) of Regulation (EC) No 726/2004.
The CMDh will be kept informed of any relevant development.
[Post-meeting note: The commission implementing decision of Tecfidera was published by the EC on 3 May 2023: You can read the Commission Implementing Decision here.
4) CMDh meeting of 23-25 May 2023
In section 4.1 on page 12 of the meeting minutes of the above meeting, it states:
The EC updated the CMDh about the regulatory actions taken following the April CMDh meetings. The EC decision for Tecfidera on the extension of the marketing protection of one additional year in accordance with Article 14(11) of Regulation (EC) No 726/2004 has been published. Regulatory actions for generic MAs of products containing dimethyl fumarate authorised via the centralised procedure are ongoing.
Timeline of events
| Timeline | Event(s) |
|---|---|
| 9 Aug 1994 | BfArM granted Fumapharm AG two marketing authorisations concerning two strengths of a medicinal product known as ‘Fumaderm’. · Fumaderm contains dimethyl fumarate (‘DMF’) and various monoethyl fumarate (‘MEF’) salts. · Fumaderm is indicated for the treatment of psoriasis. |
| The two marketing authorisations were successively transferred first to Almirall Hermal GmbH, then to Fumedica AG and finally to Biogen Idec. | |
| Oct 2003 | Fumapharm granted Biogen Idec an exclusive licence to develop and market products containing DMF. |
| 2006 | Biogen Idec acquired Fumapharm. |
| 8 Jun 2011 | Biogen Idec Ltd. lodged with the European Medicines Agency (EMA) a request for eligibility for the grant of a marketing authorisation under the centralised procedure in accordance with Article 3(2)(b) of Regulation (EC) No 726/2004. The request concerned a product containing DMF and intended for the treatment of multiple sclerosis. In the letter that accompanied that request, Biogen Idec set out the following information: · First, it stated that DMF was an active substance which had not previously been approved or assessed as a mono-substance, namely as a single component of a medicinal product, for any indication. · Second, it stated that it intended to submit a ‘full’ application for marketing authorisation i.e. an application accompanied by all the data referred to in Article 8(3) of Directive 2001/83/EC and, in particular, the results of pre-clinical tests and clinical trials. · Third, it stated that it was the holder of the marketing authorisation granted to Fumapharm in 1994 for Fumaderm, which contained DMF and MEF salts In those circumstances, Biogen Idec requested: 1) First, confirmation that the product for which it sought a marketing authorisation and which contained DMF did not fall within the scope of the global marketing authorisation for Fumaderm within the meaning of the second subparagraph of Article 6(1) of Directive 2001/83. Article 6(1) of Directive 2001/83 provides: ‘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) of Directive 2001/83. Article 10(1) provides: ‘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 [European Union]. 2) Second, Biogen Idec, also requested the EMA to confirm that, if it was approved on the basis of a full application, the product for which it sought a marketing authorisation would benefit from the data-protection period provided for in Article 14(11) of Regulation No 726/2004, irrespective of whether or not the active substance it contained, DMF, was classified as a ‘new active substance’. Article 14(11) of Regulation No 726/2004 provides: ‘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 eight-year period of data protection and a ten-year period of marketing protection, in which connection the latter period shall be extended to a maximum of 11 years if, during the first eight years of those ten years, the marketing authorisation holder obtains an authorisation for one 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.’ |
| 21 Jul 2011 | The CHMP considered that Biogen Idec’s product, containing DMF, was eligible for submission of an application for marketing authorisation under the centralised procedure on the grounds that it constituted a significant therapeutic innovation within the meaning of Article 3(2)(b) of Regulation No 726/2004. |
| 3 Aug 2011 | The EMA informed Biogen Idec that the CHMP considered that its product, containing DMF, was eligible for submission of an application for marketing authorisation under the centralised procedure. The EMA: · explained that the authorisation for a combination medicinal product was not regarded as being covered by the global marketing authorisations for the different individual active substances in accordance with Article 6(1) of Directive 2001/83. · added that, in the light of that assessment and the fact that a full development had been carried out by the applicant for its product containing DMF, the medicinal product at issue would, in principle, benefit from the data exclusivity provided for in Article 14(11) of Regulation No 726/2004, irrespective of whether or not the active substance was classified as a ‘new active substance’. |
| 28 Feb 2012 | Biogen Idec submitted to the EMA an application for marketing authorisation for Tecfidera – Dimethyl fumarate (‘Tecfidera – Dimethyl fumarate’ or ‘Tecfidera’), a medicinal product for human use, in accordance with Article 4(1) of Regulation No 726/2004. · That application for marketing authorisation contained all the data referred to in Article 8(3) of Directive 2001/83. · In that application, Biogen Idec stated, in essence, that Tecfidera was indicated for the treatment of multiple sclerosis. · In the form accompanying its application, Biogen Idec declared that its application concerned a known active substance and did not declare that Tecfidera contained a new active substance that had never been authorised in the European Union. |
| 21 Mar 2013 | In the light of all the data provided and the scientific discussions that had taken place within its organisation, the CHMP gave a positive opinion recommending that Tecfidera be granted a marketing authorisation. Following that opinion, Biogen Idec contacted the European Commission and requested that the decision granting marketing authorisation indicate that the data exclusivity provided for in Article 14(11) of Regulation No 726/2004 applied to Tecfidera, in accordance with the position expressed by the EMA in its letter of 3 August 2011 (see above). |
| 16 May 2013 | At a meeting held between the Commission and Biogen Idec. the Commission noted that: · in the decisions granting marketing authorisation, no statement was made with regard to data exclusivity, on the ground that data exclusivity was a dynamic concept subject to change in the event of a transfer of assets between companies. · added that the decisions granting marketing authorisation contained only, on the basis of the scientific assessment carried out by the CHMP, a statement regarding ‘new active substance’ status within the meaning of point 3 of Part II of Annex I to Directive 2001/83. That point provides, among other things, that ‘where the active substance of an essentially similar medicinal product contains the same therapeutic moiety as the original authorised product associated with a different salt/ester complex/derivative evidence that there is no change in the pharmaco-kinetics of the moiety, pharmaco-dynamics and/or in toxicity which could change the safety/efficacy profile shall be [provided]’ and that, ‘should this not be the case, this association shall be considered as a new active substance’. · expressed reservations with regard to the EMA’s interpretation concerning data exclusivity for Tecfidera, irrespective of ‘new active substance’ status. Accordingly, the Commission told Biogen Idec that it had one of two choices: 1) On the one hand, Biogen Idec could have allowed the Commission to adopt a decision granting marketing authorisation without a statement on ‘new active substance’ status. Since that subject was not addressed in the CHMP’s assessment report, if an application for marketing authorisation for a generic version of Tecfidera were validated, Biogen Idec would have to defend its case before the courts. 2) On the other hand, Biogen Idec could have sent a request to the Commission asking it to suspend the process of adopting the decision granting marketing authorisation and request an assessment of ‘new active substance’ status. The Commission stated that that process could take a long time and emphasised that it was impossible to predict the outcome of the scientific assessment. In conclusion, the Commission requested Biogen Idec to inform it of its preference as soon as possible. |
| 17 May 2013 | By letter to the EMA, the Commission stated, among other things, that its decision granting marketing authorisation for Tecfidera could not include a statement regarding ‘new active substance’ status in the present case as the matter had not been addressed in the CHMP’s assessment report. |
| 18 Sept 2013 | By letter to the Chair of the CHMP, the Commission stated that Biogen Idec had requested that the question of whether the active substance DMF could be classified as a new active substance be analysed. The commission: · stated that a new active substance was defined as a chemical substance that had not previously been authorised as a medicinal product in the European Union. In that regard, it referred to Annex I to the ‘Notice to applicants, Volume 2A, Procedures for marketing authorisation, Chapter 1, Marketing authorisations’ (‘the Notice to Applicants’) in the version of June 2013. · · noted that DMF had not previously been authorised as a medicinal product in the European Union, but was part of the medicinal product Fumaderm, which had been authorised in Germany in 1994. Therefore, in order to assess whether DMF was a new active substance, the Commission requested the CHMP to assess whether DMF differed from Fumaderm, which contained DMF and MEF salts. Accordingly, the Commission requested the CHMP to reconsider its assessment report with a view to including an assessment of the DMF in Tecfidera in the light of the ‘new active substance’ status. |
| 23 Sep 2013 | The EMA received the request from Biogen Idec for the DMF in Tecfidera to be classified as a ‘new active substance’. |
| 9 Oct 2013 | In an assessment report on the ‘new active substance’ status of the DMF in Tecfidera, a CHMP rapporteur took the view that DMF differed from Fumaderm, which contained DMF and MEF. However, for reasons of consistency with previous similar cases, the rapporteur requested the opinion of the Quality Working Party (QWP), that provides advice to the CHMP on the quality of medicinal products, with regard to whether or not DMF and MEF could be considered to be derivatives of each other. In a second assessment report, the CHMP’s co-rapporteur concluded that Tecfidera, which contained DMF, differed from Fumaderm, which contained DMF and MEF. However, he requested the opinion of the Quality Working Party in order to ascertain whether the latter agreed: · first, that DMF and MEF were chemically different and, · second, that DMF and MEF were not derivatives of each other. |
| 18 Oct 2013 | In a joint report, the CHMP’s rapporteur and co-rapporteur (together, ‘the rapporteurs’) considered that additional information had to be provided in support of the argument that DMF differed from Fumaderm, which contained DMF and MEF. In those circumstances, the rapporteurs raised a number of objections with Biogen Idec: · First, they took the view that Biogen Idec had to justify why MEF and DMF could not be regarded as esters and derivatives of one another. · Second, they requested Biogen Idec to address potential significant differences in terms of safety and/or efficacy, from the point of view of their properties, between the DMF in Tecfidera, on the one hand, and the mixture of DMF and MEF salts contained in Fumaderm, on the other. |
| 24 Oct 2013 | At a meeting, the CHMP raised two major objections to the request for DMF to be awarded ‘new active substance’ status. Those objections concerned: · first, establishing whether DMF and MEF were esters or derivatives of one another and, · second, addressing the relevant clinical differences in terms of safety and/or efficacy between DMF, on the one hand, and DMF combined with MEF, on the other. |
| 11 Nov 2013 | In a joint report, the rapporteurs analysed Biogen Idec’s responses and considered that the active substance DMF contained in the medicinal product Tecfidera could not be classified as a ‘new active substance’, on the grounds that it was not clear from the data provided that DMF’s properties differed significantly, in terms of safety and/or efficacy, from the product Fumaderm, which was already authorised and contained a mixture of DMF and MEF salts. |
| 21 Nov 2013 | The CHMP delivered an opinion that was revised in relation to the opinion that had been adopted on 21 March 2013. In that revised opinion, the CHMP noted that, in the Commission’s request of 18 September 2013 to have the status of the DMF in Tecfidera as a ‘new active substance’ assessed , the Commission had stated: · first, that a ‘new active substance’ within the meaning of Directive 2001/83 was a chemical substance which had not previously been authorised as a medicinal product in the European Union, and, · second, that DMF formed part of the medicinal product Fumaderm, which was authorised in Germany in 1994, but had not previously been authorised as a medicinal product in the European Union. In the same opinion, the CHMP, pursuant to Article 7 of Regulation No 726/2004, recommended, by consensus, that a marketing authorisation be granted for Tecfidera. Moreover, on the basis of an examination of the scientific evidence and in line with the clarification provided by the Commission on 18 September 2013, the CHMP took the view that DMF differed from Fumaderm, which contained DMF and MEF salts. The CHMP inferred from this that the active substance in Tecfidera, DMF, was a ‘new active substance’. |
| 26 Nov 2013 | The CHMP adopted the European Public Assessment Report (EPAR) for Tecfidera. The EPAR was published in accordance with Article 13(3) of Regulation No 726/2004. In the fourth part of the EPAR, the CHMP recommended that a marketing authorisation be granted subject to certain conditions. With regard specifically to the ‘new active substance’ status of the DMF in Tecfidera, the CHMP noted the clarification provided by the Commission on 18 September 2013. Moreover, the CHMP highlighted that, to assess whether DMF differed from Fumaderm, which contained DMF and MEF salts, it had taken into consideration Article 10(2)(b) of Directive 2001/83, which provides, among other things, that ‘the different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance shall be considered to be the same active substance, unless they differ significantly in properties with regard to safety and/or efficacy’. Lastly, the CHMP considered that MEF and DMF were both active and were not the same active substance, since they did not share the same therapeutic moiety. In that regard, the CHMP referred to point 3 of Part II of Annex I to Directive 2001/83. The CHMP inferred from this that there was no need for further investigation concerning potential significant differences with regard to the safety/efficacy profile. The CHMP concluded that the active substance in Tecfidera, DMF, was a new active substance. |
| 19 Dec 2013 | The Commission submitted a draft implementing decision granting marketing authorisation for ‘Tecfidera – Dimethyl fumarate’, a medicinal product for human use, to the Standing Committee on Medicinal Products for Human Use, in order to receive an opinion from that committee by written procedure. |
| 10 Jan 2014 | One of the members of the Standing Committee on Medicinal Products for Human Use requested that a plentary meeting that a plenary meeting of that committee be held. · That member agreed that a marketing authorisation should be granted for Tecfidera on the basis of the risk-benefit ratio. · However, he disagreed with the assessment that the DMF in Tecfidera was a new active substance, since DMF was already used – in combination with another active substance – in Fumaderm. · Despite that disagreement, he considered that Tecfidera was covered by a new global marketing authorisation, since it would not have constituted an additional strength, pharmaceutical form, administrative route or presentation of Fumaderm, or an extension thereof. |
| 28 Jan 2014 | A plenary meeting of the Standing Committee on Medicinal Products for Human Use was held in Brussels (Belgium) in order to discuss the draft Commission implementing decision granting marketing authorisation under Regulation No 726/2004 for ‘Tecfidera – Dimethyl fumarate’, a medicinal product for human use. · At that meeting, many members expressed the view that ‘new active substance’ status could not apply to a substance that was already included in a medicinal product that had already been authorised and that, consequently, DMF was not a new active substance. · In those circumstances, recital 3 of the draft Commission implementing decision was amended in order: · first, to remove the reference to ‘new active substance’ status and, · second, to state the fact that the application for marketing authorisation for Tecfidera was based on Article 8(3) of Directive 2001/83. The Standing Committee on Medicinal Products for Human Use then gave a positive opinion on that amended draft. |
| 30 Jan 2014 | The Commission adopted Implementing Decision C(2014) 601 final granting marketing authorisation under Regulation No 726/2004 for ‘Tecfidera – Dimethyl fumarate’, a medicinal product for human use (‘the implementing decision of 30 January 2014’), with a summary of the decision published in the Official Journal of the European Union on 28 February 2014 (OJ 2014 C 59, p. 1). · In recital 1 of the implementing decision of 30 January 2014, the Commission states that the medicinal product Tecfidera – Dimethyl fumarate complies with the requirements of Directive 2001/83. · In recital 2 of that implementing decision, the Commission states that it is therefore appropriate to authorise its placing on the market. · Recital 3 of that implementing decision is worded as follows: [DMF], the active substance of “Tecfidera – Dimethyl fumarate”, is part of the composition of the authorised medicinal product Fumaderm which [consists] of DMF and calcium salt of ethyl fumarate, magnesium salt of ethyl hydrogen fumarate and zinc salt of ethyl hydrogen fumarate (MEF salts), belonging to the same marketing authorisation holder. The CHMP concluded that MEF and DMF are both active and are not the same active substance since they do not share the same therapeutic moiety. Therefore, it is considered that Tecfidera containing DMF is different from Fumaderm the other already authorised medicinal product composed of DMF and MEF salts. Therefore “Tecfidera – Dimethyl fumarate”, the application of which was based on Article 8(3) of Directive 2001/83/EC, and the already authorised medicinal product Fumaderm do not belong to the same global marketing authorisation as described in Article 6(1) of Directive 2001/83/EC.’ Following the adoption of the implementing decision of 30 January 2014, a note was added to the EPAR in order to indicate that, ‘in view of [the] evolution of the regulatory considerations, as reflected in [recital 3] of the [implementing decision of 30 January 2014], the final statement in the CHMP opinion that “the active substance of Tecfidera, namely dimethyl fumarate, [was] a new active substance” [was] obsolete’. However, the CHMP stated that all the other scientific considerations and conclusions relating to its assessment remained valid. |
| 22 Jun 2015 | The applicant submitted a request to the BfArM for access to documents under the relevant German law. · That request concerned, in essence, all the documents held by the BfArM relating to the application for marketing authorisation for the medicinal product Fumaderm. · On 20 February 2017, the BfArM rejected that request on the ground that the information to which access was requested came under Biogen Idec’s trade and business secrets and Biogen Idec was opposed to such access. |
| 22 Nov 2017 | The applicant sent a new request to the BfArM for access to documents. That request concerned all the documents held by the BfArM relating to the application for marketing authorisation for the medicinal product Fumaderm. That request for access to documents also concerned a product called Panaclar 120 mg, which was intended to treat psoriasis. That product had been the subject of an application for marketing authorisation which had been filed in 2005 by Fumapharm with the BfArM and which had subsequently been withdrawn. |
| 27 Nov 2017 | The applicant submitted a request to the EMA, seeking confirmation that it was eligible to submit an application for marketing authorisation under the centralised procedure in accordance with Article 3(3) of Regulation No 726/2004 for a generic medicinal product known as Dimethyl Fumarate Pharmaceutical Works Polpharma. Article 3(3) of Regulation No 726/2004 provides that a generic medicinal product of a reference medicinal product authorised by the European Union may, under certain conditions, be authorised by the competent authorities of the Member States in accordance with, among other things, Directive 2001/83. |
| 14 Dec 2017 | By letter, the EMA acknowledged receipt of the request referred to above. · Moreover, it informed the applicant that, on the basis of the documentation provided, Dimethyl Fumarate Pharmaceutical Works Polpharma was eligible for submission of an application for marketing authorisation under the centralised procedure in accordance with Article 3(3) of Regulation No 726/2004. · Furthermore, the EMA noted that the applicant’s application for marketing authorisation would be accepted only after the expiry of the data-protection period, under Article 14(11) of Regulation No 726/2004, granted for the reference medicinal product ‘Tecfidera’, which had received an initial marketing authorisation on 30 January 2014. In that regard, the EMA referred to the implementing decision of 30 January 2014. The EMA explained that, in that implementing decision, the Commission had considered that ‘Tecfidera – Dimethyl fumarate’, on the one hand, and the already authorised medicinal product known as Fumaderm, on the other, did not belong to the same global marketing authorisation within the meaning of the second subparagraph of Article 6(1) of Directive 2001/83. · The EMA also noted that no rapporteur appointment would be made before it was possible to submit an application for marketing authorisation. · Lastly, the EMA requested the applicant to inform it, no later than seven months beforehand, of its intention to submit an application for marketing authorisation in view of the data-protection period for Tecfidera. |
| 19 Mar 2018 | The BfArM rejected the request for access to documents in the request of 27 Nov 2017 (see above) |
| 22 Mar 2018 | By letter, the EMA referred to the applicant’s letter of 27 November 2017 and informed it that, during a meeting in March 2018, the CHMP and the Pharmacovigilance Risk Assessment Committee (PRAC) had jointly appointed a rapporteur for each of them. |
| 19 Apr 2018 | The applicant brought an appeal against the BfArM’s decision referred to above (19 Mar 2018), by which the BfArM had rejected the applicant’s request for access to documents. |
| 27 Jun 2018 | The applicant submitted to the EMA an application for marketing authorisation for a generic medicinal product derived from Tecfidera. That application was amended on 5 and 18 July 2018. It concerned gastro-resistant capsules containing 120 mg and 240 mg of DMF. It was based on Article 10(1) of Directive 2001/83, which provides for the submission of an application for marketing authorisation under an ‘abridged’ procedure. |
| 11 Jul 2018 | By letter, the EMA asked the applicant to provide additional information |
| 18 Jul 2018 | The applicant replied to the EMA’s request. |
| 30 Jul 2018 | By letter (‘the contested decision’), the EMA stated, among other things, that: · According to recital 3 of the implementing decision of 30 January 2014, ‘Tecfidera – Dimethyl fumarate’, on the one hand, for which the application for authorisation was based on Article 8(3) of Directive 2001/83, and the already authorised medicinal product ‘Fumaderm’, on the other, did not belong to the same global marketing authorisation in accordance with Article 6(1) of Directive 2001/83, on the grounds that MEF and DMF were both active and were not the same active substance since they did not share the same therapeutic moiety. · Moreover, the EMA noted that, in accordance with Article 14(11) of Regulation No 726/2004, 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 that regulation are to benefit from an 8-year period of data protection and a 10-year period of marketing protection. · Thus, the EMA considered that Tecfidera clearly benefited from its own independent eight-year period of data protection and that that protection period had not yet expired. · In view of those findings, the EMA stated that the reference to data relating to the pre-clinical tests and clinical trials set out in the Tecfidera dossier was not currently authorised for the purpose of submitting an application for marketing authorisation under Article 10(1) of Directive 2001/83. · The EMA concluded that it was unable to validate the applicant’s application for the grant of a marketing authorisation for a generic medicinal product derived from Tecfidera. |
| 8 Oct 2018 | The BfArM dismissed the appeal brought by the applicant (see 19 Apr 2018 above) in so far as that appeal concerned the documents relating to the marketing authorisation for Fumaderm. |
| 9 Oct 2018 | Pharmaceutical Works Polpharma S.A (Poland), brought the present action against the EMA, supported by the European Commission and Biogen Netherlands BV (The Netherlands). |
| 13 Jul 2020 | The parties presented oral argument and replied to the oral questions put by the Court at the hearing: The applicant, Pharmaceutical Works Polpharma S.A claims that the Court should: – declare that the plea of illegality that it raises in respect of the implementing decision of 30 January 2014 is admissible and well founded in so far as, in that implementing decision, the Commission considers that ‘Tecfidera – Dimethyl fumarate’ is not covered by the same global marketing authorisation as Fumaderm; – annul the contested decision; –order the EMA to pay the costs. |
| 5 May 2021 Judgement | Following further deliberations, the judgement of the general court was delivered. In May 2021, the general court delivered its judgement (Case T-611/18) in which it declared invalid, the decision of the European Medicines Agency (EMA) of 30 July 2018 not to validate the application submitted by Pharmaceutical Works Polpharma S.A. with a view to obtaining a marketing authorisation for a generic version of the medicinal product Tecfidera. Here is the abbreviated version of the judgement. |
| 14 and 15 Jul 2021 Appeals | Three appeals brought by the European Commission, Biogen Netherlands BV (‘Biogen’) and the European Medicines Agency (EMA) seeking to have the judgment of 5 May 2021, Pharmaceutical Works Polpharma v EMA (T‑611/18, EU:T:2021:241) (‘the judgment under appeal’) set aside. By that judgment, the General Court annulled the decision of the EMA of 30 July 2018 (‘the contested decision’), which refused to validate the application submitted by Pharmaceutical Works Polpharma S.A. (‘Polpharma’) seeking to obtain a marketing authorisation for a generic version of the medicinal product Tecfidera – Dimethyl fumarate (‘Tecfidera’). Three appeals under Article 56 of the Statute of the Court of Justice of the European Union, were brought on 14 July 2021 (C‑438/21 P and C‑439/21 P) and 15 July 2021 (C‑440/21 P) By their respective appeals: -the European Commission (C‑438/21 P), -Biogen Netherlands BV (‘Biogen’) (C‑439/21 P) and -the European Medicines Agency (EMA) (C‑440/21 P) seek to have set aside the judgment of the General Court of the European Union of 5 May 2021, Pharmaceutical Works Polpharma v EMA (T‑611/18, EU:T:2021:241; ‘the judgment under appeal’), by which the General Court annulled the EMA’s decision of 30 July 2018 not to validate the application submitted by Pharmaceutical Works Polpharma S.A. (‘Polpharma’) with a view to obtaining a marketing authorisation for a generic version of the medicinal product Tecfidera (‘the decision at issue’). |
| 16 Mar 2023 Judgement | The Court: 1. Set aside the judgment of the General Court of the European Union of 5 May 2021, Pharmaceutical Works Polpharma v EMA (T‑611/18, EU:T:2021:241); 2. Dismissed the action brought by Pharmaceutical Works Polpharma S.A. in Case T‑611/18; 3. Ordered Pharmaceutical Works Polpharma S.A. to bear its own costs and to pay those incurred by the European Commission, Biogen Netherlands BV and the European Medicines Agency (EMA). You can read the full judgement of the case here. |
Further information
Primacy of national medicines marketing authorisations endorsed by CJEU adviser by Catherine Drew, Partner at Pinsent Masons (26 October 2022)
Updates
| Date | Update |
|---|---|
| 21 December 2023 | Added a new bullet point to the section The case and its outcome in brief which states that the European Commission has revoked the centrally authorised marketing authorizations for generic versions of the multiple sclerosis drug Tecfidera held by the firms Accord, Neuraxpharm, Polpharma and Teva. |
| 29 June 2023 | 1) Section The case and its outcome in brief updated to add information on the opinion of the advocate general on the appeals delivered on 6 October 2022. 2) New heading Opinion of the advocate general on the appeals plus relevant information added. 3) Comments concerning this case in the minutes of CMDh meetings are now provided in full under the heading Comments concerning this case in the minutes of CMDh meetings. The comments from the CMDh meeting of 23 – 25 May have also been added. 4) New Section Further Information added with relevant information 5) Small administrative changes made to improve readability. |
| 2 June 2023 | 1) For the sake of completeness, the last two bullet points were added under the heading The case and its outcome in brief. 2) The heading Comments concerning this case in the minutes of CMDh meetings was added. Point no 1 under this heading was already present before the heading was added. Point no 2 has now also been added. |
| 27 Apr 2023 | The following sections and relevant content were added. –Appeals to the judgement of the general court –Outcome of the appeals The Timeline of events table was updated. |
| 10 Oct 2022 | The first section of the post (before the table) has been revamped for ease of reading and understanding. |