e Submissions via EMA Gateway and Web Client

e. Submissions via EMA Gateway and Web Client An agency of the European Union

The Gateway • What is the Gateway? • Gateway Options • Key features of Web Client & Gateway (AS 2/AS 3) • Overview of Gateway Set-up • Registration • Using the Web Client • Filenaming Conventions required to submit via Gateway/Web Client

What is the Gateway? An Agency-wide solution and central transmission point for accepting secure electronic regulatory submissions over the Internet. The EMA e. Submission Gateway is a conduit, or "a route", along which submissions travel to reach their final destination. It does not open or review submissions; it automatically routes them to the relevant EMA Office. e. CTD Compliance check EMA Gateway (receives submission & sends MDN to sponsor)

e. Submissions Gateway Options • EMA Gateway Web Client – Free option – Uses applet – EMA is using European Review System (EURS) to validate the e. CTD Submissions • Gateway to Gateway (AS 2) – Applicability Statement 2 (AS 2) and AS 3 Gateway-to- Gateway – Requires an AS 2 & AS 3 compliant gateway software – EMA is using a product called Axway Synchrony Gateway Interchange (version 5. x) & EURS to validate the e. CTD submissions.

EMA Gateway Web Client Facts • EMA does not charge for the use of this solution. • ONE Web Client account is allowed per applicant. A second account may be requested though please do provide a justification to ectd@ema. europa. eu • Web Client uses Hypertext Transfer Protocol Secure (HTTPS) to ensure secure delivery of submissions over internet. • Consultancy companies can register and send on behalf of Various Applicants. • From 1 st March 2014 use of Gateway/Web Client is mandatory for all e. CTD submissions to EMA in context of Centralised Procedure.

Feature comparison of Web Client and Gateway 25 GB

Electronic Submissions Gateway Process – What to do in order to use the gateway • Determine the preferred route, i. e. AS 2/GW or GW/Web Client • To use the Gateway Web Client you need to ensure that online registration has been completed and account(s) have been activated. • Understand consult guidance documents on the e. Submission website http: //esubmission. ema. europa. eu/ • File naming convention described in the guidance document is followed correctly when uploading zip files.

Overview of Gateway Set-up Apply for Online Registration (Test & PROD simultaneously) Testing is strongly recommended for Web Client users even though it is stated Optional when registering online.

Web Client Registration - 1

Web Client Registration - 2

Web Client Registration - 3

Web Client Registration - 4

Using The Web Client 1. Logon with the credentials supplied in communication from the registration team 2. Start Submitting! Always select the ‘send documents more than 10 MB’ option to use “Large file applet”, Note that receipts (MDN) are sent only when you use this option, and this link will appear only with correct Java Version JRE 1. 5. 0_05

Technical Validation Issues • e. CTD Technical Validation identifies and rates the severity of the errors (P/F checks from the e. CTD criteria) encountered in a typical e. CTD submission, results are indicated in Final Acknowledgement message as “SUCCESS or FAILURE”. • e. CTD validation criteria valid at present is available here: http: //esubmission. ema. europa. eu/eumodule 1/index. htm • Duplicate Submission • Typo in the product number(HC 000 xxx), or a procedure number for PSURs in Single assessment(8 digit EURDID). • If an already existing sequence (in EMA database) has been modified and sent to the agency as replacement ! • Incorrect Submission structure (4 digit folder not at the root of submission package) • Incorrect submission Type

Acknowledgement Example

Key Points during the Web Client Transmission 1 There are two automated messages sent during the transmission: 1. Always use the “Large File Applet” for All transmissions via the Web Client. 2. You need to run version Java version JRE 1. 5. 0_05 http: //www. oracle. com/technetwork/javasebusiness/downloads/java-archivedownloads-javase 5 -419410. html#jdk-1. 5. 0_05 -oth-JPR 3. The Receipt is sent once the submission has been successfully received by the EMA Gateway Web Client. It is a simple text file with reception timestamp and is merely a receipt - this does not indicate a successful technical validation. To note Receipt is sent only when using the “Large File applet”. 4. The final “Acknowledgement” is an xml file sent after the system has completed the technical validation of the submission. It contains the result of the validation (SUCCESS or FAILURE). In case of a failure, a detailed description of the error is included in it.

Key Points during the Web Client Transmission - 2 5. Dependent on the submission size and web client gateway queue, both automated messages can take up to 24 hours for the Acknowledgment delivery back to the sender. 6. Where applicable, for multiple submissions, please trigger Web Client transmission belonging to same product/dossier in sequential order. • e. g. If you need to send 0033, 0035, 0036 for same product please send them in that order and allow some gap between those transmissions. Failure in following this may result in Negative technical validation. 7. All submissions should be archived as a zip file. The compressed application file must comply with the ZIP open format.

Key Points during Web Client Transmission - 3 Sender’s Inbox view showing Acknowledgement and Receipt:

Filenaming Conventions for Gateway - 1 Effective from 1 st March 2014; please use following File Name Convention for submissions Example: ESUBPXYZ_ESUBPROD_HC 000999_Wonderpill_var-type. II_0020. zip 15/03/2018

Filename to be used for ASMF • ESUBPXYZ_ESUBPROD_EMEA-ASMFxx 123_Activesubstance_asmf_00 xx. zip • ASMF holders who have on-going ASMF e. CTD life-cycle (one or multiple) related to Centrally Authorised Product(s) are strongly advised to apply for the EMEA/ASMF/xxxxx number to ensure smooth integration with the e. Submission Gateway. • You can request to apply new ASMF procedure number at the following link: http: //esubmission. ema. europa. eu/e. ASMF/index. htm

I am a supplier of ‘active substance’ for 4 Centrally Authorised Products, how should I proceed ? 1. Apply for EMEA/ASMF number -request form 2. Once you received a number, submit one new e. CTD sequence explaining in the cover letter which current CAP_ASMF you choose to carry on the life-cycle of, i. e. CAP A is at sq 0003, CAP B is at seq 0006, CAP C is at seq 0004, you would inform us that you want to follow the life-cycle of CAP B and therefore you are sending seq 0007. 3. After this submission you only have to maintain this life-cycle and it will cover all products (the others will be archived)

General ASMF submission rules • Consult ASMF guidance documentation available at: http: //esubmission. ema. europa. eu/e. ASMF/index. htm • Always submit Annexes 2 and 3 in Module 1 of the e. CTD sequence, but ensure that when submitting to EMA the relevant EMEA/ASMF/xxxxx numbers are quoted.

Filenaming Convention for Plasma Master Files (PMF)

How to Avoid Problems - 1 1. Correct Routing ID’s should be used for respective environments and reflected correctly in the Submission’s filename – e. g. ESUBPXYZ_ESUBPROD_HC 000999_Wonderpill_initial-maa_0020. zip 2. Incorrect folder structure used in Zipped file sent to EMA. Always ensure that Sequence Number(0 xxx) folder is at the root, as reflected below:

How to Avoid Problems - 2 5. Submissions should be compressed before transmission as a zip file. The compressed application file must comply with the ZIP open format. 6. Duplicate submissions: • Gateway/Web Client only processes the first submission not the duplicate. • If the first submission was in error, contact e. CTD support team at ectd@ema. europa. eu 7. Bad characters in the file names (NO Spaces!) – only underscore is allowed to separate the filenames. No other special characters are allowed. 8. Do not send duplicate submissions using both CD or DVD and Web Client. 9. Use correct Java version (JRE 1. 5. 0_05) when using Web Client.

Why should you bother? • These errors require us to manually process your gateway submission • Manually processed submissions delay access to your material • Sometimes these issues result in us rejecting your submission

Contact Information & Useful links Registration Link https: //esubregistration. ema. europa. eu/registration Registration Documentation (contact info, forms, guidance documents): http: //esubmission. emea. europa. eu/esubmission. html Technical issues during the Gateway / Web Client set-up: gatewaysupport@ema. europa. eu for Technical validation issues (e. g. ‘Failure’ Acknowledgements): ectd@ema. europa. eu TIGes Guidance on e. CTD & Nee. S: http: //esubmission. ema. europa. eu/tigesdocuments. html

Thank You for your interest! Questions?