London, 15 March 2007 Doc. Ref.: EMEA/409282/2006 Direct Line (44-20) 207 418 8467



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European Medicines Agency Post-authorisation Evaluation of Medicines for Human Use London, 15 March 2007 Doc. Ref.: EMEA/409282/2006 Direct Line (44-20) 207 418 8467 To all - Heads of the Pharmacovigilance/Clinical Trial Departments of the National Competent Authorities - Qualified Persons Responsible for Pharmacovigilance of Marketing Authorisation Holders - Responsible Persons for EudraVigilance of Sponsors of Clinical Trials Re: Change of EudraVigilance domain name and impact on electronic reporting of Individual Case Safety Reports (ICSRs) in the European Economic Area (EEA) Dear Madame/Sir, Please allow me to inform you that a new.eu internet domain for Europe (a new Top Level Domain or TLD) was launched under the responsibility of the Information Society and Media Commissioner Viviane Reding, on 7 April 2006 1,2. At the request of the European Commission, all EU institutions and bodies are in the process of changing their website and e-mail addresses to be located within the new europa.eu domain. The EMEA has performed the changeover to the new domain 'emea.europa.eu'on 4 September 2006. As a consequence, the following aspects need to be urgently taken into account for your electronic reporting of Individual Case Safety Reports (ICSRs): - The official location of the Document Type Definition (DTD) and XML Schema Definition (XSD) as referred to in the XML files (i.e. ICH E2B(M)/M2 safety and acknowledgement messages 3 ; EVMPD medicinal product messages 4 ) needs to be modified by your organisation to allow for the successful continuation of the electronic transmission of ICSRs. - The new DTD reference based on the changed domain name is now available in the test and the production environment. As of 27 April 2007 at 15:00 GMT any electronic transmissions of XML files referring to the old DTD domain name will no longer be valid. - The steps required by your organisation with regard to the changes of the domain name depend on your transmission mode (Gateway or EVWEB-Trader user). The specific technical instructions 1 See Press Release IP/06/476, Brussels, 07 April 2006 (europa.eu/press_room/index_en.htm) 2 The legal basis for the.eu TLD can be found in a Q&A doc (MEMO/06/159, Date: 07/04/2006) available in the Press Room of the European Commission webpage (europa.eu/press_room/index_en.htm) 3 ICH E2BM Maintenance of the ICH Guideline on Clinical Safety Data Management: Data Elements for Transmission of Individual Case Safety Reports and ICH M2 Electronic Transmission of ICSRs Message Specification and Electronic Standards for the Transfer of Regulatory information and data (http://eudravigilance.emea.europa.eu/human/ichandetransmission03.asp) 4 EVMPD Message and Acknowledgement Specifications Doc. Ref. EMEA/178966/2004 (eudravigilance.emea.europa.eu/human/evmpd07.asp) 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel. (44-20) 74 18 84 00 Fax (44-20) 74 18 86 68 E-mail: mail@emea.europa.eu http://www.emea.europa.eu

that need to be followed are enclosed as Annex to this letter, and are also published on the EudraVigilance website (http://eudravigilance.emea.eu.int/human/index.asp, News Section). Please liaise with your internal IT department to take the necessary preparatory steps. - With regard to the electronic transmission of the ICSRs to EudraVigilance, the changes as outlined above will have no further impact on your reporting. - With regard to the impact of the electronic transmission of ICSRs to the National Competent Authorities in Member States, we advise you to await further instructions in relation to the readiness of the authorities to process the files referring to the new domain as described in the Annex of this letter. These instructions will be published on the EudraVigilance website in due course. Please also note that the EudraVigilance website, as a result of the above changes, can now be accessed at: http://eudravigilance.emea.europa.eu If you require further information or technical assistance, please contact the EudraVigilance Helpdesk at eudravigilance@emea.europa.eu or by phone at + 44 (0) 207 523 7523. Yours sincerely, Noël Wathion Head of Unit Post-Authorisation Evaluation of Medicines for Human Use Page 2/6

Annex 1: Technical Instructions I. Instructions for all users: - The domain name "europa.eu" will replace by 1 May 2007 the "eu.int" domain name as currently used by the EMEA in all email addresses, internet addresses and URLs. From now on and until April 2007, both domain names can be used. However, from 27 April 2007 15:00 GMT onwards you can only use the "europa.eu" domain name in all your communications with the EMEA. - The email address for the EudraVigilance Helpdesk has changed to: EudraVigilance@emea.europa.eu. - The email address for EudraVigilance Registration has changed to: EudraVigilanceRegistration@emea.europa.eu. II. Instructions concerning the XML files generated by your systems: - DTDs for ICHICSR files: Your software must be modified to generate ICHICSRs that refer to the DTDs on the new domains. In particular: <!DOCTYPE ichicsr SYSTEM "http://ers.emea.eu.int/dtd/icsr21xml.dtd"> Must be changed to: <!DOCTYPE ichicsr SYSTEM ""http://eudravigilance.emea.europa.eu/dtd/icsr21xml.dtd"> - DTDs for ICHACK files: Your software must be modified to generate ICHACKs that refer to the DTDs on the new domains. In particular: <!DOCTYPE ichicsrack SYSTEM "http://ers.emea.eu.int/dtd/ichicsrack11xml.dtd"> Must be changed to: <!DOCTYPE ichicsrack SYSTEM "http://eudravigilance.emea.europa.eu/dtd/ichicsrack11xml.dtd"> - XSD for EVPRMs: Your software must be modified to generate EVPRMs that refer to the XSDs in the new domains. In particular: <evprm xmlns="http://eudravigilance.emea.eu.int/schema/evmpd" xmlns:xsi="http://www.w3.org/2001/xmlschema-instance" xsi:schemalocation="http://eudravigilance.emea.eu.int/schema/evmpd http://eudravigilance.emea.eu.int/schema/xevmpd.xsd"> Must be changed to: <evprm xmlns="http://eudravigilance.emea./schema/euevmpd" xmlns:xsi="http://www.w3.org/2001/xmlschema-instance" xsi:schemalocation="http://eudravigilance./schema/euevmpd http://eudravigilance./schema/euxevmpd "> We strongly recommend that you test out the above modifications to your system by sending some messages to the EudraVigilance pre-production environment (a.k.a "EudraVigilance Test") and perform tests with all recipients of your messages in the EudraVigilance community before putting this change live in your production systems. Page 3/6

III. Instructions on how to deal with XML files referring to the eu.int domain: - XML files (ICSRs, Acks, EVPRMs) that refer to the eu.int domain will no longer be usable after 27 April 2007, unless if the reference to eu.int is replaced to europa.eu as described above. - The EMEA will process all legacy files that are stored in the EudraVigilance database to replace the reference to eu.int to europa.eu. The original files, as submitted by you, will be stored offline for legal purposes. - If you are locally storing files that refer to the eu.int domain and will need to use those after 27 April 2007, you are advised to convert your files to refer to the europa.eu domain. A tool that can assist you in this is available on the EudraVigilance website. IV. Instructions for gateway organisations concerning the gateway configuration: Some changes which will need to be made to your gateway installation to ensure that your transmissions to the EMEA and the other National Competent Authorities in the European Economic Area and/or pharmaceutical companies are not delayed. These changes will require that you modify the domain name and/or IP address that you are currently using. The new domains will be as follows: Production: AS2 (http connections) Instead of pgateway.emea.eu.int it will now be pgateway.emea.europa.eu Instead of IP address 213.52.200.54 it will now be 195.144.18.217 AS1 (email connections) Please modify the email address for the Human EudraVigilance system to be evhuman@pgateway.emea.europa.eu Please modify the email address for the Veterinary EudraVigilance system to be evvetprod@pgateway.emea.europa.eu If you have any firewall restrictions for either AS1 or AS2 connections please update them accordingly. Pre-production(a.k.a "EudraVigilance Test"): AS2 (http connections) Instead of central.emea.eu.int it will now be pregateway.emea.europa.eu Instead of IP address 213.52.200.59 it will now be 195.144.18.219 AS1 (email connections) Please modify the email address for the Human EudraVigilance system to be evtest@pregateway.emea.europa.eu Please modify the email address for the Veterinary EudraVigilance system to be evvettest@pgateway.emea.europa.eu In both cases should you have firewall restrictions for either AS1 or AS2 connections, make sure that you update those as well. However do not remove the current allowances until after the domain transisiton period as our gateway will continue to transmit from the old domain until all partners have modified their systems. It would be advised that you contact the EudraVigilance Helpdesk to confirm that the changes have been made. Page 4/6

V. Instructions for EVWEB users only: The URL to access EVWEB pre-production (a.k.a "EudraVigilance Test") and production has changed to: http://eudravigilance.emea.europa.eu. EVWEB in pre-production (a.k.a "EudraVigilance Test") will generate XML files referring to the new domain name from 21 March 2007 onwards. EVWEB in production will generate XML files referring to the new domain name as soon as the systems of all Member States are confirmed to be able to load files referring to the new domain name, but not later than 27April 2007 at 15:00 GMT. You will be kept informed of the date of the latter via the EudraVigilance Website. Any files in your WebTrader Inbox, Outbox, Archives will be automatically converted. However, if you have downloaded any of your XML submissions to your local IT network/local PC you will need to convert these files to be able to view and use these saved files. A conversion tool will be made available at the EudraVigilance website (see section EudraVigilance Technical Documents) to assist you in doing this. See also section Instructions on how to deal with XML files referring to the eu.int domain above. V.1. E2B(M) DTD conversion tool V.1.1. Introduction The conversion tool is a simple visual basic program that will make a copy of any XML E2B(M) ICSR files in a selected directory and convert the DTD reference from the old DTD reference to the new DTD reference. Minimum system Requirements 1. Microsoft windows XP or 2000 V.1.2. Recommendations It is recommended that you only use this program on copies of any XML E2B(M) ICSR files that you wish to convert. V.1.3. Instructions 1. Unzip the file to a suitable location on your computer 2. Double click on the program file to run 3. In the application Select the directory where copies of your XML E2B(M) ICSR files are kept 4. Make sure the option New DTD is selected in the application to convert old files to the new DTD reference 5. Press the Convert files button 6. All XML files will be copied and will have the suffix "_New Domain" added to their file names, these converted files will then have the new DTD reference. V.1.4. Limitations This program will not convert neither the DTD of acknowledgment messages nor the XML schema reference of product messages V.1.5. Disclaimer This conversion tool is provided for free to use, however the EMEA will take no responsibility for any loss of data that may occur during it's use By using this conversion tool, you assume all risks associated with the use of this conversion tool, including any risk to your computer, software or data being damaged by any virus, software, or any other file, which might be transmitted or activated by it. The EMEA shall not in any event be Page 5/6

liable for any direct, indirect, punitive, special, incidental, or consequential damages, including, without limitation, lost revenues, or lost profits, arising out of or in any way connected with the use or misuse of the tool. VI. Instructions for EudraVigilance trainees only: The URL to access the EVWEB training environment has changed to: http://evtraining.emea.europa.eu. Timeline: The new domain names are currently available and can be used immediately. The old domain names can be used until Fri 27 April 2007 at 15:00 GMT. Page 6/6