Introduction
Orphan designation plays a critical role in supporting the development of medicines intended for the diagnosis, prevention, or treatment of rare diseases within the European Union (EU). Through a range of regulatory and commercial incentives, the EU orphan framework encourages pharmaceutical and biotechnology companies to invest in areas of high unmet medical need where patient populations are often small and treatment options limited.
However, the proposed revision to the EU pharmaceutical legislation is expected to introduce significant changes to the orphan medicinal product framework, including:
- updates to market exclusivity periods,
- eligibility criteria, and,
- incentives linked to unmet medical need and product accessibility across Member States.
These reforms could substantially influence regulatory strategy, development planning, and commercial considerations for orphan drug developers.
In this blog, we explore the current EU orphan designation framework, examine the proposed legislative changes, and discuss the potential impact on medicine developers pursuing orphan medicinal product designation and approval in Europe.
The revised pharmaceutical legislation
In April 2023, the European Union (EU) undertook a comprehensive evaluation of the pharmaceutical legislation. It adopted a proposal for a new pharmaceutical Directive (2023/0132)1 and a new Regulation (2023/0131)2, which revise and replace the existing general pharmaceutical legislation (Directive 2001/83/EC3 and Regulation (EC) No 726/20044). This evaluation also included a proposal to repeal the existing Orphan Medicinal Products Regulation (EC) No 141/20005, and the Paediatric Regulation (EC) No 1901/20066, and to identify strengths and areas for improvement in a new regulation.
On the 11th of December 2025, the EMA announced that the European Parliament and the Council of the European Union reached a political agreement on the reform of the EU pharmaceutical legislation. It is now undergoing a formal review by the European Parliament and the Council.
The proposed new pharmaceutical legislation has far-reaching effects on several regulatory deliverables across all stages of pre-approval medicine development, and for this article, we will discuss the effects on orphan-designated medicinal products.
We hosted a webinar outlining the key EU pre-approval regulatory deliverables required to support successful marketing authorisation and discussed how the upcoming EU pharmaceutical legislation will impact regulatory planning and medicine development.
Watch it here: ‘Future-proofing your EU regulatory deliverables and the impact of the revised pharmaceutical legislation on medicine development’.
Orphan-designated medicines
The revised pharmaceutical legislation has proposed that the Committee for Orphan Medicinal Products will cease to exist, and instead, the CHMP and the PRAC will act as the main committees.1,2
Currently, the designation criteria for a medicine to be orphan-designated are defined as a medicinal product that must address a life-threatening or chronically debilitating condition affecting ≤5 in 10,000 or one with insufficient return on investment, and it must offer a significant benefit over existing methods, if any exist.5 However, although the revised pharmaceutical legislation retains the prevalence threshold of ≤5 per 10,000, the EMA has proposed that, “via delegated acts”, it can adjust this criterion for certain diseases. For example, for rapidly fatal conditions, incidence-based criteria (the number of people affected by the condition at the time) could be used instead of prevalence.2
The revised pharmaceutical regulation also introduces the ‘breakthrough’* orphan medicinal products, which per Article 70 of the proposed regulation,2 are products that fulfil the following requirements:
- There is no medicinal product authorised in the Union for the orphan condition, and
- the use of the orphan medicinal product results in a clinically relevant reduction in disease morbidity or mortality for the relevant patient population.
* These products were previously defined as ‘high unmet medical need’ orphan medicinal products, but the definition and criteria were changed in 2026.
How will the new pharmaceutical legislation change market exclusivity for orphan-designated medicines?
Currently, when a medicinal product is granted orphan designation, the designation continues perpetually and remains in the orphan register.5 However, under the revised regulation, orphan designation is only valid for 7 years.2
Regarding market exclusivity, the EU currently grants 10 years, extendable to 12 with completion of the PIP and inclusion of the results in the product information. However, this protection may be reduced to 6 years if the criteria for orphan designation are no longer met.
The revised pharmaceutical legislation has updated the duration of market exclusivity for orphan-designated products per Article 71 of the proposed regulation2 to:
- 9 years for orphan medicinal products.2
- 11 years for breakthrough orphan medicinal products.2
- 4 years for orphan medicinal products that have been authorised in accordance with Article 13 of the revised Directive (applications based on bibliographic data).1
A ‘bonus’ 1-year market exclusivity extension can be granted, if one or more new therapeutic indications for a different orphan condition are granted, at least 2 years before the end of the exclusivity period, per Article 72 of the revised regulation.2 This prolongation may be granted twice, if the new therapeutic indications are each time for different orphan conditions.
Image source: Somerville Development Partners
Currently, if you are granted multiple different orphan marketing authorisations and for multiple indications, each indication benefits from a restart of the exclusivity clock.5 However, the revised regulation stipulates that separate orphan marketing authorisations will not benefit from additional market exclusivity. Exclusivity will start from the date of the first orphan marketing authorisation (MA), and filings for similar medicinal products, including generics and biosimilars, can be accepted 2 years prior to market exclusivity expiry (which is not the case under the current framework), per Article 71 of the proposed regulation.2
Finally, under the current system, completion of paediatric obligations can extend orphan exclusivity from 10 to 12 years if the PIP is completed prior to the expiry of the 10-year exclusivity period. Under the new framework, completion of the PIP results in a 6-month SPC extension for all products.
If you want more information on orphan drug development, we have written three blogs detailing orphan drug designations from different perspectives.
Summary
The proposed revision to the EU pharmaceutical legislation represents a major shift in the regulatory framework for orphan medicinal products and may significantly affect how companies approach orphan designation and development strategy in Europe. Changes to market exclusivity, unmet medical need criteria, and accessibility-linked incentives could create both new opportunities and additional regulatory considerations for sponsors developing treatments for rare diseases.
For pharmaceutical and biotechnology companies, understanding these evolving requirements will be essential for effective regulatory planning and long-term commercial success.
How Somerville Development Partners can help
We have supported the development and approval of numerous orphan drugs across different therapeutic areas and rare diseases. We have an expert understanding of orphan drug development and regulatory science.
We can help you:
- Compile your orphan drug designation application.
- Address challenges and respond to questions often faced by orphan drug developers.
- Demonstrate that your medicine maintains its status as an orphan medicine by submitting an orphan maintenance report.
- Compile your similarity report in preparation for submitting your marketing authorisation application.
