Learning from Case Law: Mylan IRE Healthcare v European Commission (Case C-237/22) concerning orphan medicinal products

Last updated: 10 January 2025

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This post is an attempt to to provide information on Case C-237/22 concerning Mylan IRE Healthcare v European Commission, including clarification of the concepts of “Significant Benefit” and “Clinical Superiority” for orphan medicinal products.

You can find out more about what orphan medicines are in this clip and about orphan medicines development in this webinar.

What is an orphan medicinal product in the EU?

Orphan medicinal products are intended for the diagnosis, prevention or treatment of life-threatening or very serious conditions that affect no more than 5 in 10,000 people in the European Union¹.

What is an orphan designation in the EU?

It is a status assigned to a medicine intended for use against a rare condition. The medicine must fulfil certain criteria for designation as an orphan medicine so that it can benefit from incentives such as protection from competition once on the market². 

You can read more about orphan designation here.

Parties to the proceedings:

Mylan IRE Healthcare Ltd. vs European Commission supported by the European Medicines Agency, with VVB UAB acting as intervener in the appeal.

Which medicinal products does the case concern?

The case primarily concerns two medicinal products: ‘Tobi Podhaler (an inhalation powder) – Tobramycin’ (‘Tobi Podhaler’) and ‘Tobramycin VVB (for inhalation by nebuliser) and associated names’ (‘Tobramycin VVB’).

Both products are indicated for the treatment of pulmonary infection caused by the bacterium Pseudomonas aeruginosa in cystic fibrosis patients aged six years and older³.

Background to the case

The short version

• In 1999 Novartis Pharmaceuticals UK obtained a marketing authorisation for Tobi (tobramycin) for inhalation by nebulsier for the treatment of pulmonary infection due to the bacterium Pseudomonas aeruginosa in cystic fibrosis patients
• In 2003 Chiron Corporation Ltd. was granted an ‘orphan medicinal product’ designation for Tobi Podhaler (inhalation powder) for the same condition
• In 2006, the orphan medicinal product designation of Tobi podhaler was transferred to Novartis Europharm, after its acquisition of Chiron Corporation.
• In July 2011, on the basis of that designation, the Commission finally granting marketing authorisation for ‘Tobi Podhaler – Tobramycin’, an orphan medicinal product for human use.
• In May 2014, VVB UAB submitted a marketing authorisation application for the medicinal product Tobramycin VVB (for inhalation by nebuliser) and associated names (‘Tobramycin VVB’). It applied for a derogation from the market exclusivity which Tobi Podhaler enjoyed, in accordance with Article 8(3)(c) of Regulation (EC) No 141/2000.
• In 2016, VVB UAB obtained a marketing authorisation for its product “Tobramycin VVB” (for inhalation by nebuliser).
• The decision to grant a marketing authorisation was challenged by Novartis first and continued later by Mylan after transferring rights, by which Mylan became from July 2019, the holder of the designation as an orphan medicinal product of Tobi Podhaler and of its marketing authorisation and, therefore, of the market exclusivity granted to that medicinal product) of the marketing authorisation for Tobi Podhaler⁴
• The General Court dismissed the action in its entirety (as per judgement of case T-303/16 of 26 January 2022).
• An Appeal (Case C-237/22 ) was brought on in April 2022 by Mylan IRE Healthcare Ltd against the judgment of the General Court delivered on 26 January 2022 in Case T-303/16, Mylan IRE Healthcare v Commission
• An opinion on the case C-237/22 was delivered by Advocate General Emiliou on 11 July 2024
• A judgement (on case C-237/22) of the court (Eighth chamber) was delivered on 4 October 2024.

The long version

• In 1999, Novartis Pharmaceuticals UK obtained a marketing authorisation for Tobi, a medicinal product containing the active substance tobramycin for inhalation by nebuliser, indicated for the treatment of pulmonary infection due to the bacterium Pseudomonas aeruginosa in cystic fibrosis patients⁴.
• In April 2003, Chiron Corporation Ltd. was granted an ‘orphan medicinal product’ designation, pursuant to Regulation No 141/2000, for Tobi Podhaler containing the active substance tobramycin (inhalation powder), intended, like Tobi, for the treatment of pulmonary infection in cystic fibrosis patients⁴.
• In order to obtain that designation, Chiron had to establish that tobramycin (inhalation powder) was of significant benefit to the relevant patients compared with existing therapies, including Tobi as it significantly reduced delivery time of the medicinal product compared to Tobi and it could be administered with a portable delivery system, which was an added convenience for those patients and was potentially an improvement in compliance with the treatment regime⁴.
• In 2006, the orphan medicinal product designation of Tobi podhaler was transferred to Novartis Europharm, after its acquisition of Chiron Corporation⁴.
• In July 2011, on the basis of that designation, the Commission adopted Implementing Decision C(2011) 5394 finally granting marketing authorisation under Regulation (EC) No 726/2004 for ‘Tobi Podhaler – Tobramycin’, an orphan medicinal product for human use⁴.
• As an orphan medicinal product, Tobi Podhaler enjoyed, from when its marketing authorisation was granted, a 10-year period of market exclusivity, in accordance with Article 8(1) of Regulation (EC)No 141/2000⁴.
• That market exclusivity allowed the holder of the marketing authorisation to prevent the market entry of similar competing medicinal products, subject to certain derogations. The period of market exclusivity granted to Tobi Podhaler expired on 25 July 2023.
• In May 2014, VVB UAB submitted a marketing authorisation application for the medicinal product Tobramycin VVB (for inhalation by nebuliser) and associated names (‘Tobramycin VVB’).
• Since Tobramycin VVB was similar to Tobi Podhaler, as an orphan medicinal product for the same therapeutic indication, within the meaning of Article 3(3)(b) of Regulation (EC) No 847/2000, VVB applied for a derogation from the market exclusivity which Tobi Podhaler enjoyed, in accordance with Article 8(3)(c) of Regulation (EC) No 141/2000⁴.
• In 2016, VVB UAB obtained a marketing authorisation for its product “Tobramycin VVB” (for inhalation by nebuliser), a product that is similar to Tobi Podhaler, in derogation from the market exclusivity of Tobi Podhaler based on Article 8(3)(c) of Regulation (EC)141/2000⁵.
• The MA was granted following the adoption by the Commission of Implementing Decision C(2016) 2083 final (on On 4 April 2016) concerning, in the framework of Article 29 of Directive 2001/83, the marketing authorisations for ‘Tobramycin VVB and associated names’, medicinal products for human use which contain the active substance ‘tobramycin’ (‘the contested decision’).
• In addition, Tobramycin VVB (nebuliser) is a (hybrid) generic medicinal product of Tobi (nebuliser) which is a rather exceptional situation⁵.
• The derogation of the market exclusivity was based on the fact that Tobramycin VVB was found to be clinically superior to Tobi Podhaler, given its greater safety in a substantial part of the target population (a substantial portion of the population suffering from cystic fibrosis and taking Tobi Podhaler suffered from a cough)⁵. 
• The decision to grant a marketing authorisation was challenged by Novartis first in the General Court⁵ and continued later by Mylan (Case T-303/16) after transferring rights, by which Mylan became from July 2019, the holder of the designation as an orphan medicinal product of Tobi Podhaler and of its marketing authorisation and, therefore, of the market exclusivity granted to that medicinal product) of the marketing authorisation for Tobi Podhaler⁴.
• The General Court dismissed the action in its entirety (as per judgement of case T-303/16 of 26 January 2022)⁴.
• An Appeal (Case C-237/22 ) was brought on in April 2022 by Mylan IRE Healthcare Ltd against the judgment of the General Court delivered on 26 January 2022 in Case T-303/16, Mylan IRE Healthcare v Commission
• An opinion on the case C-237/22 was delivered by Advocate General Emiliou on 11 July 2024
• A judgement (on case C-237/22) of the court (Eighth chamber) was delivered on 4 October 2024.

About significant benefit

Significant Benefit is a criterion for obtaining orphan designation (among other possible criteria mentioned in Article 3 of Regulation 141/2000). If the sponsor can demonstrate the significant benefit of a medicinal product compared to all authorised products and methods, a medicinal product can be designated as an orphan medicinal product.5

Significant benefit may be based on:

• ‘improved efficacy’ for the entire population or a particular population subset,
• ‘improved safety’ or a ‘better tolerability’ for the entire population or for a particular subset, or
• ‘major contribution to patient care’ e.g. more convenient method of administration,

About clinical superiority

Clinical Superiority  is a condition to obtain a derogation from the market exclusivity attributed to an orphan medicinal product (it is one of multiple possible conditions described in article 8 (3) Regulation 141/2000).

If an applicant for a marketing authorisation in respect of a similar medicinal product to an authorised orphan medicinal product, for the same therapeutic indication, demonstrates that the product for which the marketing authorisation is being sought is clinically superior to the existing orphan medicinal product, the marketing authorisation for the similar medicinal product can be granted.²

“Clinical superiority” is defined as:

• ‘greater efficacy’ than an authorised orphan medicinal product,
• ‘greater safety’ in a substantial portion of the target population(s),
• in exceptional cases, ‘major contribution to diagnosis or to patient care’.

What was the basis of the Appeal⁶ (Case C-237/22 ) brought on in April 2022 by Mylan IRE Healthcare Ltd against the judgment of the General Court delivered on 26 January 2022 in Case T-303/16, Mylan IRE Healthcare v Commission?

In support of its action, the appellant (Mylan IRE Healthcare Ltd) relied on two pleas in law.

First plea in law alleging an error in law in the interpretation of the concept of ‘clinical superiority’ in the sense of Article 8(3)(c) of the Regulation (EC) No 141/2000 especially in the light of the interpretation given by the General Court to the concept of ‘significant benefit’ within the meaning of Article 3 of the Orphan Regulation.⁶

Second plea in law alleging an insufficient reasoning of the General Court to base its conclusion that TOBI / Tobramycin VVB was safer than Tobi Podhaler in a substantial portion of the target population especially in the light of the content of contested decision.⁶

By its appeal, Mylan IRE Healthcare Ltd (‘Mylan’) asked the Court of Justice to set aside the judgment of the General Court of the European Union of 26 January 2022, Mylan IRE Healthcare v Commission (T‑303/16, ‘the judgment under appeal’, EU:T:2022:25), by which the General Court rejected the application – initially brought by Novartis Europharm Ltd, for which Mylan substituted itself as the applicant – for annulment of Commission Implementing Decision C(2016) 2083 final of 4 April 2016 concerning, in the framework of Article 29 of Directive 2001/83/EC of the European Parliament and of the Council, the marketing authorisations for ‘Tobramycin VVB and associated names’, medicinal products for human use which contain the active substance ‘tobramycin’ (‘the decision at issue’).⁴

An opinion on the case C-237/22 as delivered by Advocate General Emiliou on 11 July 2024

Advocate General Emiliou concluded:

For those reasons, and without prejudice to the examination of the second ground of appeal, I propose that the Court of Justice find that the General Court did not err in its interpretation of the concept of clinical superiority under Article 8(3)(c) of Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products and that the first ground of the appeal must therefore be rejected.⁷

You can read the full opinion here.

Case C-237/22 – Judgement of the court (Eighth Chamber) – 4 October 2024 

The court dismissed the appeal. You can read the judgement here. To develop a more thorough understanding of the case including the judgement, read reference no 8 below.

References:

1. Orphan Medicinal Products, European Commission
2. Orphan designation, European Medicines Agency
3. EU Judgment in Case C-237/22 P Mylan IRE Healthcare v Commission, 4 October 2024, ieu-monitoring.com.
4. Case C‑237/22, Judgement of the court, 4 October 2024, curia.europa.eu
5. Case C-237/22 of the CJEU – Clarification of the concepts of “Significant Benefit” and “Clinical Superiority”,Marc Martens et al, 9 October 2024 Bird and Bird
6. Case C-237/22 P: Appeal brought on 4 April 2022 by Mylan IRE Healthcare Ltd against the judgment of the General Court (Ninth Chamber) delivered on 26 January 2022 in Case T-303/16, Mylan IRE Healthcare v Commission -Eur-Lex
7. Case C‑237/22  – Opinion of Advocate General Emiliou delivered on 11 July 2024
8. CJEU hands down decision in Mylan orphan medicinal product appeal, Bzreth Morgan et al, 9 January 2025, Pinsent Masons.