5 September 2014
EMA/COMP/189/2001 Rev. 3b
Committee for Orphan Medicinal Products (COMP)
Note for guidance on the format and content of the
annual report on the state of development of an orphan
medicinal product
Discussion in the COMP
September 2001
Release for consultation
September 2001
Deadline for comments
December 2001
Adoption by the COMP
April 2002
Revision 1
February 2009
Adoption by the COMP
March 2009
Revision 2
March 2010
Adoption by the COMP
April 2010
Revision 3
November 2011
Adoption by the COMP
December 2011
Revision 3a - web links update
July 2012
Revision 3b - administrative update
September 2014
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Annual report on the state of development of an orphan
medicinal product
Introduction
Article 5(10) of Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16
December 1999 on Orphan Medicinal Products requires sponsors to submit annual reports on the state
of development of designated medicinal products to the European Medicines Agency (EMA).
This guideline is intended to provide advice on the preparation of these reports.
Annual reports are specific to each designation. As a consequence, when one active substance is the
subject of several designations, a separate report should be prepared for each designation.
Information to be included in the report
Administrative update
It is recommended that the sponsor uses the new template of the annual report on designated orphan
medicinal product. The template replaces all previously required documents and it is available on
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_
000343.jsp&mid=WC0b01ac0580119252&jsenabled=true.
Alternatively, a signed and dated copy of an application form (annex to guideline ENTR/6283/00)
should be submitted (updated if necessary). Sponsors are reminded that in the application form the
orphan indication and the substance name cannot be changed. If a recommended INN has been
defined by the WHO for the medicinal product, this should be indicated in the specific field.
Summary of the development of the product
The sponsor shall submit a summary of the progress in the development since the initial application for
orphan designation (for the first annual report) or since the previous annual report, including a
tabulated overview of preclinical and clinical studies initiated, ongoing, or completed in the reporting
period and a short summary of their results. This information may be extracted from an “investigator
brochure” style summary. The full study reports of non-clinical and clinical studies undertaken need
not be provided unless requested.
The sponsor should also provide a short description of the investigational plan for the coming reporting
period.
The information provided in this section should be of relevance or related to the development of the
product in the specific orphan condition as designated.
Where applicable, the sponsor should provide information on follow-up to Protocol Assistance given by
the Agency, particularly where difficulties have been encountered in the implementation of such
advice.
Note for guidance on the format and content of the annual report on the state of
development of an orphan medicinal product
EMA/COMP/189/2001 Rev. 3
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Update on current regulatory status
An update of regulatory status of the medicinal product in EU and non-EU countries should be
provided, including:
•
compassionate-use programs in the designated condition which are active (if compassionate use is
through participation in dedicated clinical trials, adequate cross-references to the previous
paragraph should be provided);
•
orphan status in non-EU countries requested, rejected or granted (with dates, countries and final
designated conditions);
•
marketing authorisation(s) in non-EU countries requested, rejected or granted for the condition
which is the subject of the orphan designation or any other condition (with authorisation dates,
countries and final indications and dates of product launch).
Information provided should include intents to apply for orphan status and/or for marketing
authorisation with planned submission dates and countries where these applications will be filed.
Incentives received
Estimates of total financial incentives or other incentives provided by the EU in terms of grants, tax
incentives, fee waivers, etc. directly related to the EU orphan designation (i.e. financial incentives
received on the one-year period covered by the report). Origin of these incentives should be broken
down by source: Member States, European Commission Directorates (e.g. Enterprise DG, Research
DG, Health and Consumer Safety DG), EMA, etc.
Calendar for submission of annual reports
These reports must be prepared and submitted to the EMA annually until the first application for
marketing authorisation within the scope of the orphan condition is submitted in the EU or
subsequently upon a specific request from the EMA. In case of negative outcome of the MA evaluation
procedure (i.e. withdrawal or refusal), submission of annual reports should resume.
Should development of a medicinal product for a designated orphan condition be terminated for any
reason, the sponsor should inform the EMA and may request to the European Commission (DG Sanco
C8 - Pharmaceuticals) the removal of the designated orphan medicinal product from the EU Register of
Orphan Medicinal Products, in accordance with Article 5(12) (a) of Regulation (EC) No 141/2000. Once
a medicinal product is removed from the Register, annual reports will no longer be required.
Timelines for submission – designations for EU
Annual reports for orphan products designated for the EU only should be submitted within 2 months
following the anniversary of the grant of the designation.
Timelines for submission – designations for both EU and US
Annual reports for orphan products designated for both the US and EU can be provided in a single
submission to the FDA and the EMA on World Rare Disease Day (last day of February) or, in
alternative, on either the normal EU or US annual reporting date.
Note for guidance on the format and content of the annual report on the state of
development of an orphan medicinal product
EMA/COMP/189/2001 Rev. 3
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Documentation to be supplied (electronic format only)
The sponsor may choose one of the following options:
1.
Submission of a single annual report form (PDF format) available on
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_
000343.jsp&mid=WC0b01ac0580119252&jsenabled=true
2.
•
Submission of the following documents:
signed and dated cover letter (PDF format) highlighting main changes in the application form since
previous annual report or the initial application;
•
signed and dated application form (Word and PDF format);
•
annual report (Word format).
The annual report and any other detailed information on the development of the product should be
submitted preferably in word-processable format. The documents should be submitted in English.
All documents should be sent electronically via the Eudralink secure mail system (with the expiry
date minimum 90 days) to orphanannualreports@ema.europa.eu.
Annual reports to be submitted also to the FDA should be sent to both
orphanannualreports@ema.europa.eu and OPDAR@fda.hhs.gov.
For further information on the Eudralink secure mail system, please contact:
eudralink@ema.europa.eu.
Additional procedural advice
If the sponsor wishes to inform about their name / address change or transfer the designation, this
should not be done in the annual report. For this purpose it is necessary to undergo the procedure
outlined in section G of the Guideline on the format and content of applications for designation as
orphan medicinal products and on the transfer of designation form one sponsor to another
(ENTR/6283/00).
To apply for the change, the sponsor should send a signed letter (PDF format) to the Agency
(orphandrugs@ema.europa.eu), with a copy to the European Commission (sanco-pharmaceuticalsd5@ec.europa.eu), listing all designations held by the sponsor and clearly indicating the new name or
address and a statement that the identity of the company remains the same. If the company's name
has changed, the sponsor should attach a copy of the certificate of incorporation.
For more information and templates please see the webpage:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_
000340.jsp&mid=WC0b01ac0580119253&jsenabled=true.
Note for guidance on the format and content of the annual report on the state of
development of an orphan medicinal product
EMA/COMP/189/2001 Rev. 3
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