Expert comment: EU pharma legislation reform – implications for orphan medicines

On 18 Mar 2026, the EU pharma legislation reform got one step closer to formal adoption, with the approval of the outcome of the related interinstitutional negotiations by the European Parliament’s Committee on Public Health (SANT).

In this article, we focus on the impact of this EU pharma legislation reform with regards to orphan medicinal products. Please note that the overview below is based on the currently available compromise texts; the final texts (post legal-linguistic finalization) still need to be prepared and adopted by the Council of the EU and the European Parliament. The key changes per the compromise texts (regulation; directive) are as follows:

Largely unchanged orphan designation criteria in practice

The designation criteria remain as follows:

• Seriousness: Human medicine for the treatment, prevention or diagnosis of a life-threatening or chronically debilitating disease; and
• Rarity: Condition affecting not more than 5 in 10 000 persons in the EU; and
• Lack of satisfactory treatment:
  • No satisfactory method of diagnosis, prevention or treatment exists, or
  • If such a method exists, the medicine must be of significant benefit to those affected by the condition.

The definition of significant benefit has been refined to specify that the clinically relevant advantage or major contribution to patient care should benefit a relevant part of the target population.

Interestingly, for the rarity criteria, the new regulation also leaves the door open for the European Commission to set specific criteria for certain conditions that would deviate from the standard ‘not more than 5 in 10 000 persons’ criteria. This would be done following recommendations from the EMA and via the adoption of delegated acts.

The eligibility criterion due to foreseen lack of sufficient return on investment is removed from the new EU pharma regulation but the impact should be minimal as this eligibility criterion has so far never been used as ground for obtaining an orphan designation.

Introduction of the concept of breakthrough orphan medicinal product

The legislation will now distinguish between 3 types of orphan medicinal products:

• Breakthrough orphan medicinal products, for which there is no medicinal product authorised in the EU for the targeted orphan condition, and the use of this orphan product results in a clinically relevant reduction in disease morbidity or mortality for the relevant patient population;
• Well-established orphan medicinal products, i.e., for which a marketing authorization is made via the well-established use / bibliography pathway;
• Other orphan medicinal products that do not fit into the 2 categories mentioned above.

Market exclusivity period affected by multiple high-impact changes

The concept of global market authorisation is introduced for orphan medicinal products, meaning that there will no longer be separate market exclusivity periods running independently from each other for each orphan indication. Rather, the first approved indication will start the market exclusivity period running for all other orphan indications.

The market exclusivity period will be 4 years for well-established orphan medicinal products, 11 years for breakthrough orphan medicinal products, and 9 years for the other orphan medicinal products.

Up to 2 years additional market exclusivity period (1 for each of the 2 new first indications) can be obtained if one or more new therapeutic indications for a different orphan condition are obtained at least 2 years before the end of the exclusivity period.

In addition, the market exclusivity period will not any more prevent the filing or assessment of a marketing authorisation application of a similar medicinal product, when less than 2 years of market exclusivity are left. This is to allow for generics and biosimilars to be available as soon as the market exclusivity period expires. Furthermore, the filing and review of a generic or biosimilar MAA, as well as the granting of said marketing authorisation, shall not be blocked, if applicable, by the market exclusivity of a similar product to the chosen orphan reference medicinal product.

Introduction of a limited validity period for orphan disease designations

Under the current orphan regulation, an orphan designation was granted for an indefinite length of time, with update reports to be submitted yearly, and an orphan maintenance application to be submitted during the MAA review process.

The new EU pharma regulation introduces a 7-year validity period, during which a marketing authorisation application (MAA) must be submitted; the orphan designation validity is then automatically prolonged to cover until the adoption of the European Commission Decision on the submitted marketing authorisation. Annual reports will not need to be submitted anymore.

This will affect both newly designated products under the new regulation as well as products already designated orphan products:

• Orphan medicinal products designated under the new EU pharma regulation: the validity period will start from the date of designation;
• Already designated orphan medicinal products: the 7-year validity period will start running from the date of application of the new pharma regulation.

An extension of the 7-year validity period can be requested and granted if duly justified, i.e., if there is evidence that relevant studies are ongoing and promising regarding a future MAA filing. If granted, the length of the extension will be determined on a case-by-case basis and tailored to bridge the gap until MAA submission.

As for the assessment of whether the designated orphan product still fulfils the orphan criteria and can therefore obtain an orphan market authorisation, this will now be subject to the same timelines as the MAA, and the assessment and its conclusions will be part of the CHMP opinion.