Author: Sam Bryant, Regulatory Affairs Manager
In 2024, the European Medicine Agency (EMA) granted orphan designation for 141 products in more than 100 different rare disease indications and orphan product developers collectively saved over €10 million through reduced regulatory agency fees.
Read on below for an in-depth look at why developers should apply for European Orphan designation, what products are eligible, when and how to submit the application.
What are the benefits of orphan designation?
The European Union (EU) offers sponsors a range of incentives for medicines that have been granted an orphan designation:
- Protocol Assistance: A type of scientific advice specific to orphan medicines that allows sponsors to get answers to their questions to allow efficient development towards a successful marketing authorisation application (MAA). Sponsors receive a 75% reduction in EMA fees for protocol assistance compared to scientific advice for non-orphan products, and for registered small or medium enterprises (SMEs), no fees are charged.
- Market exclusivity: Authorised orphan medicines benefit from ten years of protection from market competition with similar medicines with similar indications once they are approved. This period of protection is extended by two years for medicines that also have complied with an agreed paediatric investigation plan.
- Fee Reductions: In addition to the reductions in protocol assistance fees, orphan designated medicines are eligible for reductions in EMA fees for MAA, inspections, and post-authorisation activities such as variations, annual fee etc. Under 2025’s fee structure a SME developer of an orphan designated product would save over €1M in EMA fees through to granting marketing authorization, compared to a non-designated product.
- Validation of the Technology: Though not a formal benefit, a number of studies both from Europe and the US have demonstrated a positive impact of an orphan designation on both increasing company value and strengthening the ability to secure venture capital funding. Notably, the timing of an orphan application is seen as a crucial part of a company’s development strategy and serves as a signal to potential investors that the product under development holds promise and is worth consideration for investment. This signal has also been shown to result in earlier investments and overall, the orphan designation has succeeded in attracting investments to OMPs.
Orphan Designation Eligibility Requirements
A medicinal product shall be designated as an orphan medicinal product if its sponsor can establish:
- That it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than 5/10 000 persons in the Community when the application is made; Current total EU population is 448million so prevalence must be shown to be <224 000. Depending on the nature of the target indication (chronic/acute) different estimates for the prevalence may be justified.
- That there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorised in the Community. If there is an approved method, the medicinal product will be of significant benefit to those affected by that condition over the current best practice.
- The sponsor of the product must be established in the EU, MAP Group is able to take on this responsibility for your organisation if you do not yet have an entity in the EU and can transfer the designation later in development.
When to Apply?
An application for orphan medicinal product designation can be submitted to the EMA Agency at any stage of development prior to the MAA. However, since the sponsor must demonstrate the rationale for developing the product in the condition, some preliminary data from a validated non-clinical model and/or clinical data is required.
Planned submission dates: To ensure that the COMP is able to issue a decision within 90 days, as required by Regulation (EC) No 141/2000, the sponsor must submit a valid application by the submission deadlines published by the EMA.
How to Apply:
EMA strongly encourages sponsors to request a pre-submission (teleconference) meeting with the Agency prior to submitting their application. Pre-submission meetings are useful since the evaluation process has a fixed duration of 90 days and cannot be lengthened to accommodate for the lack of data or other omissions in the application. Experience has shown that they have a positive impact on the success rate of the applications.
- Costs: The fees for review of an application for orphan designation are waived by the EMA, however an administrative charge could be applied if the application is withdrawn by sponsor or not valid.
- Systems: All submissions to the EMA in relation to the orphan designation should be made by the sponsor (or their representative) through the Agency’s IRIS platform, and the product must have been assigned a Research Product Identifier (RPI). The MAP Group’s regulatory team have worked in IRIS since the portal’s launch and can act as the applicant and sponsor on your behalf.
Obligations After Designation:
- Annual Report: Sponsors must submit an annual report on development of the orphan medicine within 2 months following the anniversary of the grant of the designation or at World Rare Disease Day (last day of February). The annual report is a simplified process submitted through IRIS.
- Administrative Changes: Changes such as to the name or address of the sponsor, or the transfer of the orphan designation to another sponsor should be notified separately to the EMA, again via IRIS.
- Maintenance of Orphan Status in MAA: During the review of a MAA for an orphan designated medicine the sponsor should submit a report on maintenance of the orphan designation. This report includes data on the current prevalence of the condition to be diagnosed, prevented or treated, (which may have changed since the original designation) and enables the EMA to determine whether the medicine can maintain its status as an orphan medicine and benefit from market exclusivity.
At Kintiga, we simplify the complex journey to achieve successful patient access across Europe. By uniting deep local market access expertise, a global perspective, and innovative strategies, we partner with health technology developers to deliver impactful, tailored solutions, maximising both market potential and patient outcomes for orphan drug therapies and beyond.
For further support with understanding how these regulations and framework could impact your market access strategy, please reach out to Kintiga via enquiries@kintiga.com.
References:
https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32000R0141
