Electronic submissions Archives | European Regulatory Affairs Specialists

When will DADI application forms replace the current eAFs?

15th March 2022

The electronic application forms (eAFs) we are familiar with are in the process of being replaced later this year by a web based digital application form in a new eAF portal. The new eAF portal will look somewhat similar to the current IRIS portal.

This project, known as DADI (Digital Application Dataset Integration), is intended to be used for both CAP (Centrally Authorised Products) & NAP (Nationally Authorised Products) applications to make the future of form-filling and submission-handling more efficient at an EU level.

The Human medicinal product Variation application form will be the first to go live in DADI format. Every person involved in drafting an eAF will need to have an EMA account and user access. Companies who use consultants to prepare eAFs will need to make sure that they assign an EMA role to the consultant.

The next stages of DADI will cover the

Veterinary variation application form
Initial MAA form for Human and Veterinary products
Renewal form for Human and Veterinary products

How will it work?

The eAF will be filled in using the new eAF portal (via user interface).
The user will then finalise the eAF by generating a PDF rendition
This PDF version must still be included in the eCTD submission, as before.
It will not be possible to submit the form directly from the eAF portal

When will it happen?

As outlined in the EMA roadmap (link provided below) the two immediate key deliverables are as follows:

Key deliverables	Go-Live Time Lines
Key deliverables	Year	Quarter
Launch of Human variations web-form (parallel use of old and new variation forms as part of a Transition period)	2022	Q4 (October)
Use of variation web form only	2023	Q2 (April)

It is important for all industry stake-holders to keep up to date with the development of these new web-based forms by consulting the EMA website for updates at the various launch stages.

Where can I find information?

DADI Network Project Webinar – 18/01/2022 – Live broadcast is available here.
The updated DADI roadmap, including key milestones, is available here.
The updated version of the DADI Questions and Answers documents is available here.
The “Common factors in the Fast Healthcare Interoperability Resources (FHIR) data standard for Art57(2) and eAF”documents are available in the following link.

The project will be implemented in phases, through a set of projects known as SPOR (Substances, Products, Organisations and Referentials) data management services for Human products. The Union Product Database will be the source of data for Veterinary products.

What is SPOR?

SPOR datasets	Description of data types	Status
Substance Management Services (SMS)	Harmonised data and definitions to uniquely identify the ingredients and materials that constitute a medicinal product.	Under Development
Product Management Services (PMS)	Harmonised data and definitions to uniquely identify a medicinal product based on regulated information (e.g. marketing authorisation, packaging and medicinal information).	Under Development
Organisations Management Services (OMS)	Data comprising organisation name and location address, for organisations such as marketing authorisation holders, sponsors, regulatory authorities and manufacturers.	Operational
Referentials Management Services (RMS)	List of terms (controlled vocabularies) to describe attributes of products, e.g. lists of dosage forms, units of measurement and routes of administration.	Operational

Once the above PMS and SMS are in place, pharmaceutical companies should start preparing to replace their current data submission format in Article 57 Database from the eXtended EudraVigilance Product Report Message (XEVPRM) format to the new ISO IDMP compatible format (HL7 FHIR). Webinars and training will be provided by EMA in due course.

What do Marketing Authorisation Holders have to do at this stage?

Marketing authorisation holders need to check their data in SPOR (OMS) to ensure it is accurate and up to date. For CAPs the use of OMS data in the current eAF is already mandatory.
Marketing authorisation holders with authorised MA(s) need to check their data in Article 57 database (xEVMPD) to ensure it is accurate and up to date.

Should you need any support at this stage in getting ready for the new Application Form format please feel free to contact us & the Ivowen team will be here to help.

Written by Marian Winder

BREXIT – EVERYTHING stays the same for 2020

10th February 2020

The United Kingdom has formally left the EU as of 31 January 2020 and has become what is referred to as a third country.

On 1 February 2020 a transition period started which is due to end on 31 December 2020.

During the transition period, EU pharmaceutical law will continue to be applicable to the UK, meaning that pharmaceutical companies can continue to carry out activities in the UK until the end of 2020.

Companies have until 31 December 2020 to make the necessary changes to ensure that their authorised medicines comply with EU law and can remain on the EU market.

The UK will remain on CESP for the duration of transition period (after that, if no further extension to the transition period is proposed, it will be necessary to use the MHRA portal for submissions https://pclportal.mhra.gov.uk/)
Marketing authorisation holders and applicants can still be established in the UK in 2020
Qualified Persons for Pharmacovigilance (QPPVs) and pharmacovigilance system master files (PSMFs) can still be based in the UK until the end of 2020.
Manufacturing sites, Quality control testing and Batch release sites can also still be based in the UK until the end of 2020
orphan designation holders can still be located in the UK until 31 December 2020
minor use/minor species (MUMS)/limited markets classification holders can still be located in the UK until 31 December 2020

The withdrawal agreement foresees that following its departure from the EU on 31 January 2020, the UK will no longer participate in EU institutions and their decision-making. For the CMDh this means that as of 1 February 2020, no one who represents the UK, or is appointed or nominated by the UK can systemically participate in the CMDh meetings.

During the transition period, the UK will not be able to act as RMS in MRP/DCP, but the UK can participate in MRP/DCP as CMS.

Ivowen are here to assist you with all your Brexit related needs and dossier amendments.

For more information on Ivowen’s services and how we can help you, contact us.

Written by Alice D’Alton

2019 – What a year

6th December 2019

Ivowen attended the Medicines for Europe conference in January (Regulatory and Pharmacovigilance), the annual EuDRAcon conference in May, exhibited at TOPRA in October and joined our clients from around the world at CPhI in November.

We all saw Brexit come and go, Twice !! We wait to see what lies in store for the next deadline in January 2020.

The FMD came into effect across Europe in February in most member states.

Bulgaria joined CESP, eCTD became mandatory for all human procedures, lots of new guidance was published (to keep us all on our toes) and Nitrosamines in medicinal products moved to the top of everyone’s agenda.

With the festive season now upon us and 2020 on the horizon, Ivowen are setting our sights on the year ahead.

We will be attending the Medicines for Europe conference in January 2020 (Regulatory and Pharmacovigilance) and we encourage you to contact us before mid-January with any specific questions you might like us to ‘ask the regulators’. This is a great opportunity to ask those difficult questions that you just could not get a straight answer to in 2019, on the ever present grey areas of Regulatory procedures.

To help you to plan ahead here are some helpful updates, in brief, as full articles will be posted in 2020:

Falsified Medicines Directive – Where we are now:

Implemented on 9^th Feb 2019 in all MS except Greece, Italy and Belgium
The European Commission has produced a video to explain more about the safety features.
The HPRA have extended the use and learn period, initially to Sep 2019 and extended it again to end on a phased basis starting from 31st January 2020.
The MHRA is also taking a pragmatic, flexible approach to how they enforce the new legal requirements.

Nitrosamines

Step 1: MAHs should conduct a risk evaluation to identify products at risk of N-nitrosamine formation or (cross-)contamination and report the outcome by 26 March 2020 at the latest.
EMA guidance can be found at https://www.ema.europa.eu/en/human-regulatory/post-authorisation/referral-procedures/nitrosamine-impurities-overview
CMDh guidance can be found at https://www.hma.eu/226.html#c6548

Ivowen are here to assist you in 2020 and will continue to provide the top quality service you have come to expect from us.

For more information on Ivowen’s services and how we can help you, contact us.

Written by Alice D’Alton.

Ivowen attended TOPRA Symposium 2019

30th October 2019

This year’s TOPRA Annual Symposium was held in Dublin in October. The Annual Symposium is an essential meeting for regulatory professionals to gain both an understanding of current and evolving regulatory requirements, as well as insights into future plans for regulations in the Human medicines, Veterinary medicines and Medical Device sectors.

Three members of our Team attended the Symposium this year, Majella Ryan, Alice D’Alton and Nanda Naik. This year was particularly satisfying for Ivowen as we had an exhibition stand at the three day event.

As well as exhibiting, Ivowen attended the sessions including ‘Life after Brexit’. This session was a live discussion of predictions and concerns about the possible outcome of ongoing negotiations with the EU.

Now that an extension has been granted, which will delay the UK exit until January 2020, we are left wondering if we will finally know the UK position when Ivowen attend the Medicines for Europe regulatory conference being held in Amsterdam on 29^th – 31^st January.

In the meantime, we await instruction from the regulators on whether UK will still be available on the CESP portal later this week. Ivowen is registered on the new MHRA submissions portal so either way we have you covered.

Ivowen will keep you up to date in the coming days and weeks

Please contact us, Ivowen are dedicated to keeping you up to date with the latest regulatory updates and innovations. We remain at your disposal to assist in all of your regulatory endeavours today and into the future.

Written by Alice D’Alton.

eSubmission Roadmap updated

26th August 2019

The European Union updated its eSubmission Roadmap in June 2019 to reflect changes in timelines.

What is it?

The eSubmission roadmap is a high level, strategic plan for business and technology changes within the EU. Its function is to align the plans and implementation timelines of target groups and stakeholders, including the EMA, National Competent Authorities (NCAs) and the pharmaceutical industry.

Full details on the eSubmission Roadmap are available on the EMA’s eSubmission website here.

What is happening?

Centralised Procedure(s) (CP)

It is mandatory since January 2010 that all submissions in the CP are made in the eCTD format

National Procedure(s) (MRP & DCP and national only procedures)

It is mandatory since July 2015 and January 2017 that all submissions for new MAAs using the DCP and MRP respectively are made in the eCTD format. For purely national procedures, eCTD has been mandatory for new MAA submissions since July 2018.

For all new submissions in MRP and DCP, the mandatory use of eCTD has been in force since January 2018, and for all new national submissions, since January 2019.

What does this mean?

This means that ALL submissions in the EU for human medicinal products now have to be made in eCTD format. Are you ready? If not, contact us to find out how we can help switch all your current MAs to eCTD and manage all your lifecycle needs. Ivowen has been eCTD compliant since 2009, and therefore has a wealth of experience to become your key partner in this vital step of your registration process.

If you need any clarification or support to manage the changeover to eCTD, Ivowen will gladly work with you to ensure a seamless and efficient transition to eCTD. Contact us for more information or to make an enquiry.

Written by Majella Ryan

2018 02 eSubmission Roadmap final slide v2.0 Feb 2017.

eCTD is coming…

7th February 2018

All good (and bad) things, must come to an end. The NeeS (Non-eCTD electronic submissions) submission format, will no longer be accepted for any Marketing Authorisation applications (MAAs) or submissions in MRP or DCP from 1^st January 2018. Centralised Procedure (CP) submissions have been mandatory in eCTD since 2010. All new MAAs submitted using either the Decentralised Procedure (DCP) or the Mutual Recognition Procedure (MRP), have had to be in eCTD format since the middle of 2015. As of 1^st January 2018, all MRP submissions must be submitted in eCTD. Therefore, if your application/product is not in eCTD format and you need to submit an MRP variation, you have to transition to eCTD for the next submission.

What is the timetable?

Starting from 1^st January 2018 it is mandatory for all CP, DCP and MRP submissions to be in eCTD format. For national procedures (NP) the deadline is currently set at 1^st July 2018 for new MAAs.

Following quickly behind these requirements, all submissions in CP, DCP, MRP and NP will have to be in eCTD from January 2019. At this stage, the exact date is not confirmed, but you need to be ready.

We can help…

Ivowen can create a baseline dossier for any submission based on currently approved information. Currently, baselines are not mandatory but some Member States are requesting them. In addition, it is best practise to get your dossier into a baseline for all future submissions.

Ivowen can transition your application to eCTD at the next regulatory activity (variation, renewal, Article 61.3, etc.).

Ivowen can manage the eCTD lifecycle for you in-house and provide you with fully valid, submission-ready sequences.

Contact us for more information or for help with building your eCTD now.

EMA eSubmission Gateway – tips & tricks

28th August 2017

Current State of Play

As many of you know, the EMA eSubmission Gateway/Web Client has been mandatory for all submissions for human medicinal products made through the Centralised Procedure since March 2014 and for veterinary products since January 2017. In addition, all PSUSA/PBRER submissions are also made through this EMA eSubmission Gateway, and have been mandatory since June 2016.

Unfortunately, as many of you also know, there are some glitches and issues with this portal. Below are the workarounds for some of these glitches.

Contact us

Please feel free to contact us if you need any help submitting through the EMA eSubmission Gateway/Web Client

“Click to send documents totalling more than 10 MB”

To send any submission through the portal and get an acknowledgement (“ACK”) for this submission, you have to use the “Click to send documents totalling more than 10 MB” option. When you first log in or register for the EMA eSubmission Gateway, and go to the “SEND DOCUMENT” page, this option is not available. This is down to Java settings and security. The way around this is to set your Java security settings and exceptions as follows:

At the moment, you may find that the “Click to send documents totalling more than 10 MB” option is still not available, even when your security settings and exception list are correct. The EMA Service Desk has assured me that they are working on this issue, but in the meantime you can follow the instructions below to work around this issue/

Open Internet Explorer and log into EMA portal. Go to “Send document”.
If you see the “Click to send documents totalling more than 10 MB” then continue to send your submission as normal.
If you don’t see the “Click to send documents…” link, like this example, then follow the instructions below:

3.1 In the top right hand corner is a Settings button that looks like a machine wheel

3.2 Click on this Settings button and then click “F12 Developer Tools”:

3.3 If you see that the Document Mode is “11 (default)” like the screenshot below:

3.4 Change this to “10” and the “Click to send documents…” will appear:

3.5 You need to leave the F12 Developer Tools window with these settings OPEN until you have completed your submission. The EMA Gateway Service desk is working on a fix for this problem, but this is the workaround for now.

Ivowen hosts 2017 conference

14th June 2017

Dublin, the venue

It was our pleasure to host the EuDRAcon conference for 2017 in Ireland on 1^st and 2^nd of June. We welcomed representatives from 21 Member States, including our new member from Cyprus, Nicolas Constantinou from Niconex Medical. EuDRAcon currently has participating members in 25 of the current 31 EEA member states, plus Switzerland, providing unrivalled EU/EEA coverage and support.

We were also grateful to Kevin Horan, Director of ICT and Business Services, HPRA who participated and provided us with valued insights into the future of ICT in the EU.

What was discussed

The discussions included

an overview of local requirements specific to Cyprus (MAAs, PV, fees, pricing and reimbursement),
a summary of a recently successful Article 29 referral to the CHMP
Electronic submission roadmap
ISO IDMP
Substance, Product, Organisation, Referential (SPOR)
Regulatory Optimisation Group of HMA – background and work plan
BREXIT – what it means to us

For more information on any of our services, please contact us.

CESP expands in Poland and Greece

5th April 2017

Latest news from Poland and Greece for CESP

From 3^rd April 2017 it will be possible to submit the following procedures via Common European Submission Portal (CESP) to Poland:

Initial Marketing Authorisation Applications (MAAs)
Variations
Renewals

The submissions may concern national and European procedures (MRP, DCP) both for human and veterinary medicinal products.

Also from 3^rd April 2017 the following submissions should be transmitted through CESP for Greece:

All submissions for Mutual Recognition/Decentralised Procedures (MRP/DCP)
national procedures relating to approvals, variations, renewals, PSURs, ASMFs etc., as well as any other documentation should be submitted using CESP.
Responses to deficiencies and any other additional information that can be requested from the EOF within the claims of assessment.

What does this mean for you?

To date in Poland, only submissions concerning initial MAAs were possible via CESP. There are still some national requirements in Poland, however. All documents that require an original signature can be either submitted

in electronic version with a valid electronic signature or
must be submitted in parallel to CESP in paper.
Documentation once submitted via CESP should be submitted via this channel throughout its whole lifecycle.

For submissions into Greece, additional CD/DVDs are no longer required. In addition, for each submission, a corresponding reference number will be automatically assigned and will be sent directly to the applicant.

Where can I find more information?

Full details are available on the Polish Ministry’s website (in Polish) here.

Full information is for Greece (in Greek) here.

We can help…

Ivowen are fully equipped to prepare and submit any applications on your behalf. Please contact us or our EuDRAcon partners for more information and for support of your dossier compilation or updates.

Written by Majella Ryan

Points to note on the eAF

3rd February 2016

General

The eAF is mandatory for all procedures from 01/01/2016 (CP, MR, DC, National in eCTD/NeeS/Paper). However, Presubmission Meeting Requests, Article 61(3) & MAT forms remain the outside scope and can be submitted as paper or PDFs.

Please contact us if you require any assistance with any of the forms or any advice on any of the above procedures. For your convenience, the following is a summary of the important aspects of using the eAF.

Always check the e-submission website for the latest version of the eAF (http://esubmission.ema.europa.eu/eaf/)
- Word versions will be removed from Notice to Applicants in January 2016
- After 11/01/2016 only version 1.19 will be acceptable for new procedures
- eAF should be printed for Paper submissions
- Version 1.20 is planned for April 2016 (unless hotfixes are required before then)
- It is important to note, and welcome news, that there is no need to update to a newer version of the eAF in the middle of a procedure
- See the guidelines (update planned in January 2016) and release notes (lists the changes made to newer versions) for further information
- In line with the proposed move towards a Single Submission Portal (SSP) in place of CESP and the EMA Gateway, there are plans to reformat the eAF into a data capture system that can be submitted directly through CESP. This is in a very preliminary stage.

Technical queries should be sent to EMA Service Desk via IT service portal (login)
- Q&A documents should be consulted first
- Fast web view warning in the dossier validation report for the eAF can be ignored

Procedural queries should be directed to the National Competent Authority (NCA) (and response sent to EMA Service Desk). Complicated queries should be sent to both parties.

Webinars are available for the NCAs (to try to reduce the requests for MS specific national requirements)

Using the eAF

Technical Validation of the form (internal):
- Once signature is added and form validated, it is now locked. Locked forms cannot be amended. Therefore, the signature should be the last thing added to the form.
- Always keep a copy of the unlocked form so that amendments can be made (e.g. during preparation or for requests from NCA for updated forms during a procedure)
- Do not use bookmarks as these may cause invalidation issues

Annexes to the form should be filed separately in module 1.2 (do not use the PDF function to insert them into the eAF)
- Form should be named; cc-form-eaf-var
- Annex should be named; cc-form-annex-var (e.g. cc-form-5-19 or cc-form-proofpayment)

Electronic signature can be an image of a real signature (e.g. jpeg file – a scanned copy of wet signature. This however is not an electronic signature and is only used to close/lock the form) or can also be a line of text which states that signature is on file internally (e.g. “This form was authorised following company policies by Majella Ryan, Regulatory Affairs Manager of Ivowen with authorisation to sign. The signature is on file”)
- The eAF does not accommodate multiple signatures at present. A separate annex should be provided if multiple signatures are mandatory for a particular NCA. Multiple name sections will be incorporated into version 2.0 but no mention of whether multiple signatures will also be accommodated.
- The signature should be provided by the responsible MAH or can be provided by any authorised deputy
- Please also check national requirements for signatures.
- See Q&A guidance for further information

Workaround solutions (e.g. Annex B for multiple MAH or Product names) should always be mentioned in your cover letter
- Some unforeseen variations (category z) are not adequately accounted for yet. Details of such changes should be outlined in the scope section of form and in the cover letter.
- Duplicate sections only if products differ with regard to API or Pharmaceutical Form
- Annex A or Annex B can be used for multiple MAH or Product names. Click on Annex A/B button in form and add the annex as a separate file in Module 1.2
- Detailed instructions on 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 – if you need more advice contact EMA Service Desk.

No translations of the eAF are available, nor should they be requested.

Drug substances can be entered from controlled vocabulary lists or free text, and these each have different EV codes.
- The focus should be on using substance, product, organisation and referential (SPOR)

Request for New Terms:
- EUDRACT terminology used
- Use eAF Term Request form to request new terms
- Send it to mdms@ema.europa.eu only
- Response should be received within 5 working days

Strikethrough text function is not available in eAF but text can be copied and pasted (with text struck through) from Word or Outlook

In MRP/DCP one common application form is highly recommended, one per pharmaceutical form or strength for all member states in case of new MAA and one eAF for all involved products for all member states in case of variations and renewals.

Written by Majella Ryan

When will DADI application forms replace the current eAFs?

BREXIT – EVERYTHING stays the same for 2020

2019 – What a year

Ivowen attended TOPRA Symposium 2019

eSubmission Roadmap updated

What is it?

What is happening?

Centralised Procedure(s) (CP)

National Procedure(s) (MRP & DCP and national only procedures)

What does this mean?

eCTD is coming…

What is the timetable?

We can help…

EMA eSubmission Gateway – tips & tricks

Current State of Play

Contact us

“Click to send documents totalling more than 10 MB”

Ivowen hosts 2017 conference

Dublin, the venue

What was discussed

CESP expands in Poland and Greece

Latest news from Poland and Greece for CESP

What does this mean for you?

Where can I find more information?

We can help…

Points to note on the eAF

General

Using the eAF

Need help with all the regulatory jargon?

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Our Policy

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