1. EU SUBMISSION BY
Haripriya
&
Revathy

2. EU Specification Application no: Alpha numeric values
Application Types:
New Active Substance
Abriged Applications
Biological and Biotechnological Products
Active Substance Master File

3. EU Specification Types of Application procedure
1 Centralized Procedure
2 National Procedure
3 Mutual Recognition procedure
4 Decentralized Procedure

4. File formats
PDF v 1.4 except where specific Agency requirement for later version (e.g. application form)
Product Information texts
PDF, RTF.
Some NCAs request MS Word documents but when provided these should not be referenced in the xml backbone. Usually provided in a separate folder on the same CD/DVD.

5. EU Module 1
Specifies region-specific administrative and product information.
Electronic signatures is not fully supported by EU.
Directory and file structure is common for 4 procedures.
“eu-backbone” contains 2 elements “eu-envelope” and “m1-eu

6. EU Module 1
Sections in Module 1 which have to be placed in Country sub directories
1.0 Cover Letter
1.2 Application Form
1.3.2 Mock Up
1.3.3 Specimen
1.3.4 Consultation with Target Patient Groups
1.3.5 Product Information already Approved in Member States
Additional Data
Responses
1.3.1 Product Information has both Country/Destination (cc) and Language sub directories

7. EU Module 1
For MRP, DCP and NP,documents for each country are placed in an appropriately named subdirectory.
The folder name "common" should only be used for documents
applicable to all EU countries.
In module the document should be placed in appropriate language subdirectory.
The 'Additional Data’ section should only be used for for NP, MRP and DCP; it is not generally applicable for the CP.

8. EU Envelope Envelope is designed for all type of submissions.
“eu-envelope” provides the metadata at the submission level.
It may contain several envelope entries, each related to a specific country.

9. Envelope Example

10. Node Extensions
Node extensions are a way of providing extra organisational information to the eCTD.
visualised as an extra heading in the CTD structure and should be displayed as such when the XML backbone is viewed.
Node extensions must not be used where ICH specified subheadings already exist
Node extensions must only be used at the lowest level of the eCTD structure.

11. Node Extensions
The content associated with a node extension can be placed in a separate sub folder in the submission.
Node extensions must be maintained over the entire life of the eCTD lifecycle
Node extensions may be nested as this is allowed by the eCTD DTD e.g. in Module 5.3.7

12. Node Extensions

13. File Naming Convention
File names in Module 1 have the general structure CC-FIXED-VAR.EXT.
Example:fr-outer-tablet10mg.pdf
File name path length should not exceed maximum 180 characters.

14. Submission types Initial marketing authorisation
Supplemental information
Follow-up measure
Specific obligation
Variation type 1a
Variation type 1b
Variation type 2
Periodic Safety Update Report
Renewal
Active Substance Master File

15. Centralized Procedure
CP is administered by the European Medicines Agency (EMEA) in London.
EMEA has established two scientific committees for human and veterinary products.
Committee for Human Medicinal Products for Human Use(CHMP)
Committee for Veterinary Medicinal Products(CVMP)
The member states have one representative in each committee
Single application which, when approved, grants
marketing authorisation for all markets within the European Union.

16. Centralized Procedure
Mandatory for biologics, gene therapy products, monoclonal antibodies, products in certain therapeutic areas and orphan drugs
Optional for innovative products
For cp the single envelope for EMEA.
For the Centralized Procedure, the country subdirectory is always named "emea" and language subdirectories in Module have the appropriate language identifier.

17. National Procedure
The pharmaceutical industry could apply for a national approval
The product can then only be sold in that particular EU country
Parallel national submissions is not allowed.
A marketing authorisation (MA) is valid for five years and after the first renewal, the MA is valid for an unlimited period.
To get approval for the product , SPC is the basis for marketing of the product.

18. Mutual Recognition Procedure
Mutual recognition means that EU countries may approve the decision made about a medicinal product by another EU
country.
The two working groups for the MRP are CMD(h) and CMD(v).
If a member state cannot approve the assessment report , pre-referral procedure should be issued by the relevant Co-ordination Group
The Member State(s) fail to reach an agreement during the 60-day procedure of the pre-referral, a referral to the CHMP/CVMP for arbitration may be made through its secretariat at the EMEA.

19. MRP
National approval of RMS

20. MRP
Managing a combined sequence for all NCAs

21. MRP
Managing individual sequences for each NCA

22. Decentralized Procedure
The decentralised procedure should be used for products that have not yet received authorisation in an EU country.
The applicant may request one or more concerned Member State(s) to approve a draft assessment report, SPC, labeling and package leaflet as proposed by the chosen reference Member State in 210 days.
The two working groups for the MRP are CMD(h) and CMD(v).
If a member state cannot approve the assessment report , pre-referral procedure should be issued by the relevant Co-ordination Group
The Member State(s) fail to reach an agreement during the 60-day procedure of the pre-referral, a referral to the CHMP/CVMP for arbitration may be made through its secretariat at the EMEA.

23. DCP
If there is a request for an update concerning Modules 2-5 or a common part of Module 1, the applicant should provide the updating sequence to the RMS and all CMSs.

24. DCP
If the validation update concerns information regarding country-specific information (e.g. an application form) then this should be provided to the specific CMS only.

25. DCP
If there are validation updates for both common and country-specific information then these can be combined in a single sequence and provided to the RMS and all CMSs.

26. COMPARISION

27. Differences

28. PIM PIM (Product Information Management)
Currently pilot scheme running
Increasing efficiency of exchange of PI
Improving quality
Centralised Procedure only initially

29. eCTD Tracking Table Principles of Layout for the Tracking Table
The Member State acting as the RMS should be identified and be the first Member States listed.
The ‘first wave’ CMSs should be listed alphabetically and grouped under a heading ‘CMSs - First Wave
Subsequent waves should be grouped under a similar heading e.g. ‘CMSs - Second Wave’, ‘CMSs - Second Wave’ etc. and listed alphabetically

30. eCTD Tracking Table
The RMS and CMSs should be identified by the two character country code
provides information about the content of an eCTD sequence including the date when it was submitted to the Reference Member State and affected Concerned Member States.
Tracking tables can be submitted in XML or PDF format in the cover letter section of Module 1.

31. eCTD Tracking Table

32. LIFE CYCLE MANAGEMENT
For initial submission new documents only included.
For later submissions the documents are updated by using operational attributes.
The operational attributes are
New
Append
Replace
Delete

33. LCM ADVANTAGES
Ability to show relationships between dossiers and manage complex lifecycle
Ability to see at any time the current documentation for a product
Standardisation and harmonisation of information provided
Electronic workflow
Ease of access to correct information for evaluation
Harmonisation of the regulatory process
Consistency of format.

34. THANK YOU