Applying for orphan designation

The European Medicines Agency (EMA) provides information and guidance to sponsors on applying for an orphan designation for a medicine.

Click on the image below to view a guide (flowchart) for the orphan designation process for potential sponsors.

Click to download the full image as PDF

Sponsors need to use EMA's secure online IRIS platform to submit applications for orphan designation and to manage pre- and post-designation activities:

For information and guidance on using IRIS, see the IRIS homepage.

Sponsors should follow one of the two options below to submit an application for orphan designation:

• Submit directly an application to EMA, through the IRIS system:

Pre-submission meetings are not mandatory and sponsors are welcome to send an application for orphan drug designation without notice. However, EMA would appreciate it if sponsors could send the application a few days before any of the published submission deadlines available on the EMA website to allow more time for the validation process and the possibility to intervene in case of technical problems.

• Request a pre-submission meeting/teleconference:

EMA strongly encourages sponsors to request a pre-submission meeting with the Agency prior to filing an application. Pre-submission meetings usually take place via teleconference, unless the sponsor has a strong preference to come to EMA in person.

If a sponsor feels they could benefit from a preliminary discussion before the submission of an orphan drug application, they can request a pre-submission meeting/teleconference at least two months prior to their planned submission date via the IRIS portal. This should allow enough time for the organisation and any amendment of the application as recommended by EMA.

Sponsors should create an initial draft application for orphan designation before creating the application for the pre-submission discussion. These are two separate submissions to be made in the IRIS system. The draft submission for orphan designation should be populated with the relevant data and documents, but not submitted, at least one week before the pre-submission meeting date.

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.

Sponsors should use the forms below to apply for orphan designation:

• Template for sections A to E for the scientific part of the application for orphan designation
• Translations required with the submission of an application for orphan medicinal product designation

Information to refer to:

• Guideline on the format and content of applications for designation as orphan medicinal products and on the transfer of designations from one sponsor to another
• Procedural advice for orphan medicinal product designation : Guidance for sponsors submitting an application
• Points to consider on the calculation and reporting of the prevalence of a condition for orphan designation
• National registers of authorised medicines

In particular, when completing section A.3.2 'Plausibility of the orphan condition; rationale for use of the medicinal product', sponsors should clearly identify studies with the substance in a relevant model(s) of the condition and, if possible, preliminary clinical data in patients with the condition.

Each application is assigned two coordinators:

• one member of the Committee for Orphan Medicinal Products (COMP);
• one scientific administrator from the EMA secretariat.

Applications for orphan designation are free of charge.

EMA will validate the application and will send the sponsor a validation issues letter explaining if the application is found to be invalid or incomplete. Once the validation is complete, the Agency will send a timetable for the evaluation procedure to the sponsor.

EMA advises sponsors developing advanced therapies to apply separately to the Committee for Advanced Therapies (CAT) to have their medicine classified as an advanced-therapy medicine. For more information, see advanced-therapy medicinal product classification.

Parallel application with international regulators

EMA encourages parallel applications for orphan designation with regulatory authorities outside the EU.

EMA has special arrangements with regulators in the United States and Japan for this purpose. If an application has not been submitted to the:

• United States before, EMA advises sponsors to apply for an orphan designation from the United States Food and Drug Administration (FDA). EMA and the FDA interact and collaborate regularly in the 'clusters' for 'Orphan medicinal products' and 'Rare diseases'.
• Japanese authorities before, EMA encourages the sponsor to seek orphan designation from the Ministry for Health, Labour and Welfare (MHLW) in Japan. Under the Japanese orphan designation system, the MHLW provides consultation on orphan designations before submission, whereas marketing-authorisation applications submitted following an orphan designation are assessed by the and the Pharmaceuticals and Medical Devices Agency (PMDA). The MHLW generally seeks scientific counsel from the PMDA on the orphan designation.

After submission, the two coordinators prepare a summary report on the application, which is circulated to all COMP members and discussed at the COMP's next plenary meeting.

At this stage, the COMP will either adopt a positive opinion or raise a list of questions and invite the sponsor to an oral explanation at the next COMP plenary meeting.

The COMP should adopt an opinion by day 90 of the procedure. It forwards this to the European Commission for adoption of a decision.

If the COMP's opinion is negative, the sponsor can appeal.

The European Commission will issue a decision on a COMP opinion within 30 days of receipt. Following a decision:

• EMA publishes information on the orphan designation;
• the European Commission enters the orphan designation into the Community register of designated orphan medicinal products.