Publication date: January 09, 2026
Much of the EU’s pharmaceutical legislation was adopted over 20 years ago. It is clear that much progress has been made in this area since then. Furthermore, due to the nature of European Union legislation, these regulations are fragmented into numerous smaller regulations and directives. To address both of the aforementioned issues, in 2023, the European Commission presented a draft of new legislation in this area. This draft was called the Pharmaceutical Package. After publishing the draft regulation and directive, the European Parliament adopted the draft with amendments at first reading in 2024. Since then, negotiations have been ongoing with the Council of the EU on the final shape of the regulations. However, on December 16, 2025, the Council published the outcome of the negotiations, announcing that both legislative bodies had reached a preliminary agreement on the final shape of the regulations.[1] Now, the draft will be put to a vote by the EU Council, where, probably after introducing the agreed amendments, it will be sent back to the Parliament, which will have to accept the amendments.
The new Regulation will repeal most of the existing pharmaceutical law regulations, including Regulations No. 141/2000 and No. 2004/726. The draft also assumes a complete consolidation of the previous regulations, including the Commission implementing regulations, which clarified some provisions. For the purposes of this article, the current orphan drug system is based on Regulation No. 141/2000, so the proposed changes will alter the current system. An undeniable limitation of this article is that the comments will only concern the draft regulations and the materials accompanying the draft, which do not formally constitute binding legal provisions.
Chapter VI of the draft Regulation [2] establishes new provisions for orphan medicinal products. Although the new Regulation repeals previous legislation, there are significant similarities in the format of the regulations.
Definition of an orphan medicinal product
The original definition of an orphan medicinal product consisted of three separate criteria, the first two of which were alternative and the third were cumulative. Article 63 of the draft Regulation significantly simplifies the definition of an orphan medicinal product by establishing two cumulative criteria: the medicinal product is intended for the diagnosis, prevention, or treatment of a life-threatening or chronically debilitating condition affecting no more than five in 10,000 persons in the Union at the time the application is submitted; and there is no satisfactory method of diagnosis, prevention, or treatment of the condition officially authorized in the Union, or, if such a method exists, the medicinal product will bring significant benefit to patients suffering from the condition. Unlike the original Regulation, there is no reference here to the criterion of lack of prospects of return on the necessary investment.
Furthermore, as part of the regulatory consolidation, the criterion of “significant benefit” has been defined at the level of the Regulation, not the Commission Regulation. A significant benefit means a clinically significant benefit or a significant contribution to patient care when a product is used, if such benefit or contribution benefits a substantial and relevant proportion of the target population.[3]
The label award procedure and incentive system
The new regulations completely remove any reference to the Committee for Orphan Medicinal Products, where, according to the draft, the European Medicines Agency will be responsible for the entire procedure. [4] The procedure itself and the formal application requirements have not undergone significant changes. The new orphan medicinal product designation will be valid for seven years,[5] during which the sponsor will be entitled to benefit from the incentive scheme. According to the new draft, the designation ceases to be valid upon obtaining a marketing authorization. It can also be withdrawn at the sponsor’s request. [6] The Register of Orphan Medicinal Products will be maintained by the Agency.
Under the new regulations, the sponsor of an orphan medicinal product has the obligation, not just the right, to request advice from the Agency regarding tests, trials, product quality, how to demonstrate the product’s significant benefit, and how to demonstrate clinical superiority compared to products with market exclusivity. [7] Paragraph 2 of this article also establishes that the sponsor of an orphan medicinal product also has access to the EU incentive system, as was the case previously.
Access to the centralized procedure
The process for obtaining marketing authorization for orphan medicinal products has not undergone significant changes. Orphan products can still be authorized through the so-called centralized procedure, which allows for a single authorization valid throughout the EU.[8]
Breakthrough orphan drug product
A significant departure from the current regulations is the introduction of a completely new concept: the “breakthrough” orphan medicinal product. In the original draft, such a product was to be called an orphan medicinal product meeting a high unmet medical need. However, following agreements between the Parliament and the Council, the name will be changed to a “breakthrough orphan medicinal product.”[9]
A breakthrough orphan medicinal product is a product intended to treat diseases for which there is currently no available drug treatment, provided that the following requirements are met: there is no approved medicinal product for the orphan disease in the EU; and the introduction and use of the orphan medicinal product leads to an exceptional therapeutic advance, a clinically significant reduction in morbidity or mortality in a given patient population.[10] The Agency is tasked with developing scientific guidelines for the implementation of this provision.[11] Designation as a breakthrough product is particularly important with respect to the period of market exclusivity.
Period of market exclusivity and extension of the period
The base period of market exclusivity for orphan medicinal products is currently 10 years.[12] Under the new regulations, the default period will be 9 years.[13] However, breakthrough orphan medicinal products will be entitled to 11 years of market exclusivity. However, for orphan products authorized under Article 13 of the amended Directive 2001/83/EC, this period will be only 4 years.[14]
As is the case under the current system, market exclusivity is not an absolute prohibition. Exceptions to the general prohibition remain unchanged and include: consent from the marketing authorization holder; the marketing authorization holder for the original orphan medicinal product is unable to supply sufficient quantities of the medicinal product; or, the second applicant can establish in the application that the second medicinal product, although similar to the orphan medicinal product already authorized, is safer, more effective, or otherwise clinically superior to the first. Definitions of similar medicinal product and clinical superiority are also included in the Regulation. A similar medicinal product means a medicinal product containing a similar active substance or substances as those contained in the currently authorized orphan medicinal product and intended for the same therapeutic indication. Clinical superiority, on the other hand, means greater efficacy, greater safety, or other significant contribution to diagnosis or patient care.[15]
The period of market exclusivity may be extended by a further 12 months if, at least two years before the end of the exclusivity period, the entity responsible for marketing the orphan medicinal product obtains a marketing authorisation for one or more new therapeutic indications for another orphan disease. Such extension may occur a maximum of two times if the new therapeutic indications concern other orphan diseases.[16]
[1]European Parliament, Deal on comprehensive reform of EU pharmaceutical legislation < https://www.europarl.europa.eu/news/nl/press-room/20251209IPR32110/deal-on-comprehensive-reform-of-eu-pharmaceutical-legislation > accessed 16.12.2025.
[2] Position of the European Parliament adopted at first reading on 10 April 2024 with a view to the adoption of Regulation (EU) 2024/… of the European Parliament and of the Council laying down Union procedures for the authorization and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency , amending Regulation (EC) No 1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC) No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No 1901/2006.
[3]Article 2, paragraph 7 of the Draft Regulation.
[4]Article 64 of the Draft Regulation.
[5]Article 66 of the Draft Regulation.
[6]ibid.
[7]Article 78 paragraph 1 of the Draft Regulation.
[8]Article 16 paragraph 1 of the Draft Regulation.
[9]European Parliament, Background note: pharmaceutical package provisional agreement elements < https://www.europarl.europa.eu/news/en/press-room/20251209IPR32111/background-note-pharmaceutical-package-provisional-agreement-elements > accessed 22/12/2025.
[10]Article 70 paragraph 1 of the Draft Regulation.
[11]Article 70 paragraph 3 of the Draft Regulation.
[12] Article 8 paragraph 1 of Regulation No 141/2000.
[13]Article 71 paragraph 2 (a) of the Draft Regulation.
[14]Article 71 paragraph 2 (c) of the Draft Regulation.
[15]Article 2, paragraph 8 of the Draft Regulations .
[16] Article 72 paragraph 2 of the Draft Regulation.