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.
Apply using the 'IRIS' system
EMA has published two guidance documents on how to use the new system:
- IRIS quick guide to registration
- IRIS quick guide to the portal for orphan industry users
- Procedure for orphan medicinal product designation: Guidance for sponsors submitting an application via IRIS secure online portal
EMA first launched IRIS in June 2018 and optimised the system based on feedback from users during a three-month pilot phase.
IRIS reduces the time needed to prepare and submit applications. Users can check the status of applications from any device and receive automatic notifications when the status changes.
It is part of a longer-term EMA programme that aims to make the handling of product-related applications easier and utilises the domains of master data in pharmaceutical regulatory processes (SPOR).
EMA plans to extend the IRIS system to cover other procedures, including Parallel distribution, and will publish further information as soon as available.
Step 1. Ensure your active substance is recognised
It can take just a few minutes to check the EUTCT, but if you need to request the inclusion of a new active substance, EMA can usually approve this request within four working days.
For more information see:
Step 2. Ensure you have an active EMA account
To check if you have an EMA account or obtain a new one, visit EMA's Account Management portal.
If you already use an EMA-hosted application, your EMA account is active and you can use the same credentials to log into IRIS.
It can take just a few minutes to check, but please allow up to two working days if you need to reset the password for an account for which you have not set up your secuity questions.
For more information see:
Step 3. Ensure your organisation is registered with EMA
To use IRIS, your EMA account needs to be associated with an industry organisation registered in EMA's Organisations Management Service (OMS).
To check if your organisation is registered, access the OMS via EMA's substance, product, organisation and referential (SPOR) portal.
It can take just a few minutes to check, but if your organisation needs registering in the OMS, EMA can usually approve this within five working days.
For more information see:
Step 4. Ensure your account gives you access to IRIS
Your organisation must have at least one person assigned an Orphan Industry 'User Admin' role to access IRIS. This may be you or someone else.
If this role is not yet assigned, the appropriate person must request it using EMA's Account Management portal. Please factor in time to submit the request and allow up to two working days for EMA to approve it.
To access IRIS, you need to request an Orphan Industry 'Manager' or 'Contributor' role, depending on the permission level you require, using EMA's Account Management portal. You must provide your Organisation ID number, and your 'User Admin' needs to approve the request.
It can take just a few minutes to request the user role, but please factor in the time for approval within your organisation.
your organisation is registered with EMA
For more information see:
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 provide the draft application for the pre-submission discussions via the IRIS system one week in advance.
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
Documents 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, 27 March 2014 (currently under review to reflect changes introduced with the IRIS system)
- Points to consider on the calculation and reporting of the prevalence of a condition for orphan designation
- Recommendation on elements required to support the medical plausibility and the assumption of significant benefit for an orphan designation
- Data providers and sources to identify existing authorised medicinal products in the European Union and European Economic Area
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.
Evaluation of applications
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.
European Commission decision
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 under rare disease (orphan) designations;
- the European Commission enters the orphan designation into the Community register of designated orphan medicinal products.