eCTD Archives | European Regulatory Affairs Specialists

You need to apply Type IA Annual Reporting in the EU in 2025

15th April 2025

The Type IA Annual Update, also known as the “Annual report”, is a single submission of all the Type IA variations (not requiring immediate notification) which have been implemented during the previous twelve months.

The Annual report should be submitted as close to 12-month deadline as possible, but ultimately no earlier than 9 months and no later than 12 months after the first implementation date of the Type IAs included in the report.

Meaning of implementation for type-IA variations:

For quality changes, ‘implementation’ is when the company makes the change in its own quality system.

This implementation date must be carefully planned and recorded to facilitate submission of your Annual Reports.

How to plan the submission of your Annual Report:

As submission of the Annual report is dependent on the implementation of the first type IA variation, its submission date can change every year.

It is very important to note that the Type IA Annual report must fulfil the variation conditions for grouping (or super-grouping if it concerns more than one marketing authorisation).

It is expected that Type IA variations included in an Annual report will not be rejected. However, if rejected, Type IA variations from the annual report can be resubmitted as individual Type IAs immediately (outside of an annual report).

CMDh confirmed that although not specified in their guidance, Type IA variations implemented before 1 January 2025 can still be submitted as single type IA variations according to the current rules. The EMA confirmed that Type IA variations implemented in 2024 and not submitted to the Agency by 31 December may also be submitted by MAH no later than 12 months after implementation.

Therefore, Type IA variations implemented from 1 January 2025 should be submitted as part of the Annual report.

Type IAs can still be submitted outside the Annual report in the following cases:

If they are part of a grouped Type IB or Type II variation
If they are part of a super-grouping variation
If it involves the resubmission of a Type IA variation previously refused in the Annual report (12-month reporting period is criteria in this situation)
In exceptionally cases which should discussed and agreed with the EMA/NCAs.

eAF:

There are no current plans to amend the eAF to reflect Annual Reporting, instead, Applicants are advised to include a note in the cover letter and an additional note in the eAF scope to clarify that the application relates to the Annual Update of Type IA variations e.g. as foreseen in the updated Cover letter template:

<Annual update of type IA variation(s)

[X] We confirm that the annual update is submitted within 12 months following the implementation of the first type IA variation applied for in this notification. Implementation date of the first type IA variation: >

If you need any assistance with planning and submission of your Annual Reports, contact us and we will be happy to help.

Written by

Fiona Downey

Fiona Downey 1

Back to Basics – The Risk Management Plan (RMP)

19th July 2024

The Risk Management Plan (RMP) documents the risk management system considered necessary to identify, characterise and minimise a medicinal product’s important risks.

The RMP should be updated throughout the life cycle of the product, for example;

if there is a change in the list of the safety concerns
when there is a significant change in the existing additional pharmacovigilance activities
if an emerging safety issue is confirmed.

The RMP should be assigned a new RMP version number and a date each time it is updated and submitted for assessment.

An updated RMP can be submitted as a standalone [currently C.I.11] variation, when necessary, but it is most often submitted as a consequence of or part of another variation.

The format and content of the RMP should follow the RMP template; Guidance on the format of the risk management plan (RMP) in the EU – in integrated format which consists of seven parts.

For a generic medicinal product, hybrid products and/or fixed combination products with no new active substance the safety concerns should be aligned to those of the originator product that are available;

either from the originator’s approved RMP
or from the list of safety concerns of the substance published on the CMDh website.

RMPs are approved per each medicinal product, not per MAH, therefore only one RMP should be submitted for an MRP or DCP with different MAHs. The RMP must remain identical in RMS/all CMS throughout the product life cycle.

The RMP should be provided in eCTD section 1.8.2. To facilitate the assessment a ‘tracked changes’ version of the RMP, in Microsoft word, should also be provided in the ‘working-documents’ folder outside eCTD.

The QPPV’s actual signature or the evidence that the RMP was reviewed and approved by the QPPV should be included in the finalised approved version of the document; for eCTD submissions this would be the RMP submitted with the last eCTD sequence of the procedure (usually the closing sequence).

UK RMP: The MHRA states you can either submit a GB/UK RMP or use the approved EU RMP with the GB/UK specific annex attached. Further information of UK RMP can be found on the MHRA website and their Guidance note on good pharmacovigilance practices.

Feel free to contact us here at ERA to assist you with all things regulatory in Ireland, UK and across the EU.

We take the pain out of regulatory so that you can take your medicine to the next level.

Written by

Fiona Downey

Fiona Downey 1

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

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.

Company Announcement – Majella Ryan FTOPRA

17th October 2018

Majella Ryan FTOPRA

Ivowen are pleased to announce that Fellowship of The Organisation for Professionals in Regulatory Affairs (FTOPRA) has been conferred on Majella Ryan. According to TOPRA:

“The award of a Fellowship is intended to recognise a contribution in which the individual has used his/her professional knowledge and experience to influence, guide or develop the profession in a proactive way.
While clearly the individual’s regulatory experience and current senior position achieved are important, what is also looked for is a consistent record of activities or influences extending beyond the confines of the individual’s day-to-day activities.”

Majella Ryan has been in the regulatory affairs business for over 20 years and in this time has worked in both small and large multi-national companies, setting up Ivowen in 2002. Since then, Majella was involved in the set-up of TOPRA in Ireland, acting as the inaugural Chair in 2001/2011, as well as speaking at various conferences and providing extensive regulatory training to companies around the world. In addition, Majella is actively engaged in the publication and explanation of regulatory and guidance updates via Ivowen’s website, and via Ivowen’s EU network, EuDRAcon. As part of Ivowen’s daily work, Majella is involved in the high level regulatory strategy and support of complex projects and products like biosimilars, paediatric investigation plans and clinical trials, eCTD implementation, regulatory pathways to approval, Brexit planning, and much more.

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

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.

New EU MA Applications will require eCTD Submissions by Q3 2015

21st April 2015

Marketing Authorisation Applications for human use submitted using the Decentralised Procedure (DCP) will need to be provided electronically as eCTD by Q3 2015. Submission in eCTD for Mutual Recognition Procedures (MRP) will also be required by the start of 2017, and finally National Procedures by the start of 2018. eCTD is already required for Centralised Procedures.

The EMA also announced at the end of 2014 that Veterinary Drugs must be filed electronically starting in 2016 for CP/DCP, and all submissions by 2017 by VNeeS (Veterinary Non-eCTD Electronic Submissions).

Plans are also underway to replace the Microsoft Word-formatted application form with the eAF (Electronic Application Form) and the deadline will be Q1 2016. Further detailed guidance can be found under the following links:

European Medicines Regulatory Network eSubmission Roadmap

eSubmission Roadmap flow chart

Ivowen are fully eCTD-ready and compliant. Please contact us for more information and for support of your electronic applications.

Written by Laura Oakey