eCTD Archives | European Regulatory Affairs Specialists

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.

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.

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.