0. Webinar for the usage of an eAF at NCA level
eAF new MAA
Webinar for the usage of an eAF at NCA level
Presented by: Georg Neuwirther, Klaus Menges and Kristiina Puusaari

1. Agenda
Overview and Status of Implementation Speaker: Georg Neuwirther (AGES, chair eAF MG)
Processing the eAF for initial application Speaker: Kristiina Puusaari (EMA), Klaus Menges (BfArM)
Questions and Discussion

2. Overview and Status of Implementation

3. eAF Maintenance Group (eAF MG)
Group of business and IT-experts from NCAs, EMA and Industry
eAF MG is in charge of implementing the eAF according to the eSubmission Roadmap
Evolution: 1. word AF eAF –- 3. Single Submission Portal
Please contact us via for any questions!

4. Background eSubmission Roadmap
(reflecting final adopted version 1.0 dated 07/11/14)
Ongoing/optional
Mandatory
draft eSub Roadmap
NCA & industry survey
eSub Roadmap Adoption
Use of eCTD v.4
All submissions in CP (human) in eCTD
All submissions in CP, DCP and MRP (human) in eCTD
Use of NeeS and eCTD in DCP and MRP (human)
New MAA in DCP (human) in eCTD
New MAA in DCP and MRP (human) in eCTD
All submissions in MRP (human)
All other MRP submissions (human)
Use of VNeeS in CP, DCP and MRP (vet)
New MAA in CP and DCP (vet) in VNeeS
All submissions in CP, DCP and MRP (vet) in VNeeS
All other in CP and all MRP submissions (vet)
eGateway (CP)
(human and vet)
eGateway (CP, human)
Single submission portal - combined CESP/Gateway
in CP (human)
Single Submission Portal with integration of eAF
for all submissions (human and vet)
CESP (human and vet)
Single submission portal - combined CESP/Gateway
in all other procedures (human and vet)
Use of eAF in all procedures (human and vet)
in CP
eAF in all procedures (human and vet)
in all other procedures
NCA use of Common Repository for CP submissions (human)
NCA use of Common Repository for all CP submissions
(human)
Use of PSUR Repository for CAPs and NAPs (human)
Use of PSUR Repository for all CAPs and NAPs
(human)
eSubmission Roadmap Timelines

5. Status eAF usage in CP
Successful start of compulsory usage of the eAF for Centralised Procedures (all types, human&veterinary). Transitional period ended on the 1st of September; applicants are be requested to resubmit using eAF only if other formats are received (scanned eAF/ word)!
CESP (human & vet)
Single submission portal - combined CESP/Gateway
Fully functional
single submission portal for all submissions (human & vet)
eGateway (CP)
(human and vet)
eGateway (CP, human)
(Mandatory for CP-human, optional for other procedures)
Use of eAF
in CP
eAF in all procedures
in MRP/DCP

6. Option 1 - link to eAF webpage from Eudralex page
Where to find eAFs?
Option 1 - link to eAF webpage from Eudralex page
Notice to Applicants (European Commission)
6/index_en.htm
Option 2
eSubmission Homepage (EMA)

7. Release Plan of eAFs
Release Plan published here: Excerpt of Release Plan (status )
Milestone
Date
Publication of eAF V 01.19
09/11/15
Replacement eAF V by 01.19
30/11/15
Publication of eAF V 01.20
08/03/16
Replacement eAF V by 01.20
04/05/16 - TBC

8. Important Documents

9. National translations of the eAF
eAF-MG was asked by a member state to provide translations of the eAF
Conclusion after discussion in the eAF-MG and after consultation of the chair and co-chair of ITDEC 1) The eAF-MG has only the mandate to provide the existing application forms in the new PDF-technology, in English
2) The eAF-MG has to follow the endorsed eSubmission Roadmap

10. What to do at NCAs level (key steps)?
Check IT infrastructure (Adobe Version 10 or above)
Ensure compatibility of business systems with EUTCT terms
Check connectivity to EUTCT (search for substances)
Update internal guidelines and offer internal trainings
Same content new functionality
Implement automated data import
Pilots in AT, DE, IT, ..

11. Processing the eAF for Initial application
eAF support structure
Impact of mandatory use
Receipt and validation
What to do in case of issues
Locking the form and signatures
How to check whether eAF is locked
Navigation and blocks/context (grey border)
Check eAF compliance
Controlled terminology and Term Request Process
Workarounds
Form validation
Areas, which might cause difficulties when extracting data: Closure, container, material …
XML contains invisible data (CR for 1.20)

12. eAF- Support Structure
Effective support for applicants & NCAs/EMA will be a key success factor during the implementation phase of mandatory use of the eAF for all EU procedures!
Why will support be needed?
Technical change from Word to PDF format
eAF structure cannot be changed by the applicant like Word forms
Majority of free text fields have been replaced by controlled vocabularies – terms are selected from EUTCT-catalogues – if terms are no available they should be requested through MDMS new term request process
Paper form was an isolated document with no direct IT- integration into the business process (e.g. for automatic data import). Now eAF data will be used directly in IT- systems reducing manual workload and human error

13. eAF- Support Structure
Technical questions, comments, change requests – forward the applicants/MAHs to
Procedural questions
CP –
MRP/DCP/NP– if questions are received by EMA the applicant is advised to contact the RMS/relevant NCA
Mixed queries containing both technical and procedural queries received directly by RMS/NCA – RMS/NCA can forward the reply to and EMA will complete response with the technical details and will reply to the applicant with NCA in copy
Mixed queries containing both technical and procedural queries received by EMA – EMA will reply to the user providing response on the technical issue and will direct the applicant to RMS/NCA for the procedure aspects
In case the RMS/NCA is not sure of the reply they can always forward the queries to

14. eAF- Support Structure
(no big differences to the AS-IS-situation)

15. eAF – Impact of mandatory use
Impact on NCA staff
Preparation
Please remind applicants during pipeline/pre-submission meetings on the upcoming mandatory use for all MRP/DCP/NP applications
If you receive queries from applicants/MAHs regarding variations and renewals, please remind them of the mandatory use. You can provide them a link to eAF document introducing the mandatory use published on the eSubmission website
Remind applicants that the eAFs should be submitted as ‘real’ eAFs – meaning that they are kept in electronic format and are submitted with the xml. Forms that have been printed and scanned as PDF lose all their intelligent features and become flat PDFs. These do not allow import/export of xml data into receiving systems
Remind applicants/MAHs that there is no further transitional period regarding the usage – the forms are already available from the eAF website

16. eAF – Impact of mandatory use
Impact on NCA staff
Preparation
The mandatory use of the eAFs does not change any existing wet signature requirements by the NCAs – only the form changes – i.e. instead of the word or pdf version of the AF available in the NTA Eudralex website the only forms available are the PDF eAFs
These PDF eAFs can be read just like any other PDF document and receiving them doesn’t require special tools at the NCAs – Adobe v.10 is the only requirement

17. eAF – Receipt and validation
All applications received after 1 January 2016 should be received in eAF format
You can recognise the eAFs easily as they look different from the NTA paper forms, see example below of :
the Initial H-MAA:
eAF Paper form

18. eAF – Receipt and validation
the Initial V-MAA:
eAF Paper form
Note: The error in the European Commission header for the initial V-MAA eAF has been noticed and will be updated in the next release of the eAF.

19. eAF – What to do in case of issues/problems
If you cannot open the eAF – contact your IT service desk as soon as possible to confirm you have the correct version of Adobe installed in your PC.
If you cannot see all fields in the eAF – see example of the same form displayed differently depending on the PC settings below – please contact your IT service desk as soon as possible to have the correct version of Adobe installed on your PC.
Issue with Adobe/EURS or browser plug-in eAF with correct PC set up

20. eAF – locking of the form and signatures
If you have received an eAF that has been filled, printed, signed and scanned as PDF you should inform the applicant and inform them that it is very important to use the eAF correctly i.e. sign the form electronically and not as a ‘flat PDF’ – information from flat PDFs cannot be uploaded to your receiving systems.
How to recognise if the form has been saved as ‘real eAF’ or if it is a scanned copy of the eAF?
The text in the ‘real eAF’ is greyed out
The ‘Form validation’ page is present in the form (the last page) (see below)
At the bottom of the ‘Form validation’ page you are able to save form, print form, export XML and update lists but all other buttons have been disabled
If the form hasn’t been ‘locked’ by the applicant and you are able to make changes to the form, you should inform the applicant to ensure they lock the form in future to prevent regulators making unintentional changes

21. eAF – locking of the form and signatures
In process once the signature image has been added
Once the form has been saved and was locked
The image could be an image of a real signature as well

22. Navigation
unlocked
locked

23. Identification of entered data
Proposed to used bolded text or grey background for data fields

24. eAF – controlled terminology
The dropdown lists or selections from catalogues include terms according to standardised nomenclatures and quality standards for medicinal substances and products of EDQM or the EUTCT system
In case of a missing term – as a general rule – in order to complete an eAF, please use the eAF Term Request Form. Once completed, you will need to submit your form via to
A provisional term may be added to the list within 5 working days; however, please note that there is a possibility that the term might not be approved and ultimately added to the list for future use. For further guidance please refer to ppt
In case NCAs identify an inappropriate term used the applicant must correct it and should ask for a provisional term according to the defined process

25. eAF Term Request Process
In case MAH/NCA will ask for new terms
 EMA provides a standardised request procedure available on the eAF website
(day 0)
MAH fills in request form and s request to
Term request evaluation process
(+5 day)
MDMS Service desk informs MAH of term to be used
* In the term request form there are detailed instructions on what information is required to apply for changes in each list.

26. eAF Term Request Process – 5 days SLA

27. eAF – workaround solutions
The most commonly used workaround solution used by the applicants/MAHs would be an addition of an annex to the form as the relevant section cannot be filled as required in the eAF - these are not the annexes as referred to in section 5 of the initial forms
The annex must be included as a separate, clearly named document in the same folder (e.g. 1.2 in EU M1) where the application form is provided! We recommend that the annex is named as per the section of the form that is provided in the annex.
The standard PDF functionality of adding an annex using the paperclip function must not be used as the annexed documents will not be visible when viewed via eCTD review tool (e.g. EURS)

28. eAF – workaround solutions
Detailed instructions how to use workaround solutions is available in the eAF Q&A document and the eAF Technical Guidance documents – both are published on the eAF webpage – you can always refer the applicants to these documents and if they need more advice refer them to
If you (repeatedly) receive a question that is not responded to in the guidance documents, please provide the question and the relevant response to with title ‘New question to be addressed in the eAF guidance’ and we can add the question in the Q&A document and add additional guidance in the eAF Technical Guidance document during the next update of that document
The forms have been built so that they contain build in business rules, guiding the applicants to fill in the forms the correct way and this might in some sections compromise flexibility, however, the forms remain flexible and there are multiple different ways to fill in several sections depending on each specific application. EMA directs MAHs to NCAs/RMS when there are questions on how to fill in certain parts of the forms for MRP/DCP/NP applications to ensure there are no content validation issues

29. eAF – form validation
All eAFs contain built in business validation based on complex validation rules – occasionally NCAs identify that some business rules related to MRP/DCP are not correct and should be changed – in these cases please report to as soon as possible to raise a change request
Ideally, all validation errors are solved before finalising and locking the form – remind applicants it’s very important to save the unlocked forms before closing them in case there are any validation issues and updated form is requested – it is not possible to change already locked forms and in case no unlocked version has been saved the applicant might have to refill the whole form in order to make changes to meet the validation comments
Occasionally it is not possible to solve all validation comments and once the forms are locked the form will display the number of ‘form validation errors’ at the very end of the form – however it is not possible to see to which sections these validation errors refer to. Validation errors in the form can, in most cases, be ignored as often refer to sections for which the applicant has provided an annex for.

30. eAF – form validation
The form validation is not a technical eCTD or NeeS validation
Leaving validation errors in the form does not affect eCTD or NeeS validation - the purpose of this validation is simply to guide the applicants to fill in the form correctly and to fill in mandatory fields of the forms
In many cases, form validation errors do not lead business validation errors
Form that doesn’t have any form validation errors might still be invalidated during the business validation step – it’s important not to confuse form validation with business content validation!
If a new version of the forms has become available / entered into force between the receipt of the application and request for supplementary information (validation comments) the applicant doesn’t need to change the form version (unless this has been the case in the past with paper forms)

31. CTLs for containers, closures, devices
Short lists of controlled terms might raise problems to describe the item precisely
Missing term list requires additional quality checks and causes additional workload
145 national terms registered

32. CTLs for containers, closures, devices
17 terms in EUTCT versus 45 national terms
38 terms in EUTCT versus 220 national terms
32 terms in EUTCT versus 190 national terms

33. XML seem to contain invisible data
Especially in section “1. Type of Application” data entered in the form will remain visible when the corresponding fields are un-ticked, e.g. you added data for a centralised procedure, but un-tick the button to switch to data entry for mutual recognition procedure. To reduce the risk of accidental data loss it was decided to ensure sections completed then hidden would persist. Data may only be deleted on a field by field basis by users.
Concern was raised that these hidden data could be processed in case of automation or when extracted manually.
It seems that these “hidden data” will not be processed as the corresponding root xml value is set to 0, in that case for CP, and details in the data fields below will be ignored.
If the analysis is wrong, unwanted data usage need to be blocked definitely.

34. XML seem to contain invisible data
This „0“ will switch off use of data. In the unlocked form, the data can still be used in case of intentional re-thinking your decision.
It does not matter whether data entered in the below XML elements in case of processing.

35. What to do at NCAs level (key steps)?
Check IT infrastructure (Adobe Version 10 or above)
Ensure compatibility of business systems with EUTCT terms
Offer internal trainings
Same content – different functionality
Update internal guidelines!
Check connectivity to EUTCT (search for substances) Not needed if you only read eAFs
Implement automated data import
like AT, DE, IT, ..

36. Contact
Please send any questions to or the responsible NCA contact