Submissions in NeeS (Non-ectd electronic Submission) format will soon be history with the possibility of submitting in this format ending definitely for all procedures in the EU member states end of 2018.
Currently, electronic submissions of dossiers for human medicinal products in the EU are acceptable in two formats: NeeS (Non-ectd electronic Submissions) and eCTD (electronic Common Technical Document). eCTD differs from NeeS in that an eCTD dossier contains two XML files (index.xml and EU-regional.xml) providing a backbone to the dossier, and a util folder, together allowing easy navigation through the dossier and replacement of documents, while navigation through a NeeS is based on an electronic Tables of Content, bookmarks, and hypertext links.
eCTD was first established in 2002 and became mandatory for all centralized electronic submissions to EMA by 2010. The National Agencies, however, allowed a longer transition period to transfer national, decentralized procedure (DCP) and Mutual Recognition Procedure (MRP) dossiers from NeeS to eCTD. For new marketing authorization applications submitted via the DCP and MRP, eCTD format has become mandatory since 2015 and 2017 respectively, while variations for older approved dossiers can still be submitted in NeeS. The European Medicines Regulatory Network eSubmission Roadmap, adopted in 2014 and modified in February 2017, describes the transition from NeeS to eCTD (v.3.2).
Source: eSubmission Roadmap
From 1 January 2018 onwards, eCTD will be mandatory for all CP, DCP and MRP submissions. The eSubmission Roadmap has been extended for national procedures, but European national submissions for new applications will be required in eCTD format from 1 July 2018 as well and the NeeS roadmap will definitely end on 1 January 2019 with eCTD being required for all submissions, including those for nationally registered products. This implementation date set should be strived for by all National authorities (see Annex 2 to the HMA eSubmission Roadmap).
Although this is not a strict requirement, authorities will request transferring the existing dossier to eCTD format prior to submission of a new variation or update. The creation of an eCTD is done via a baseline submission, usually only covering the Quality part (Module 3) of the dossier. A baseline submission is a compiled submission of the current status of the dossier, i.e. resubmission of currently valid documents that have already been provided to an agency but in another format (TIGes Harmonised Guidance for eCTD Submissions in the EU Version 2.0 August 2011). The advantage to the company of creating a baseline eCTD first is that this will provide a well-structured overview of the information already contained in the dossier. As a result preparing the individual future submissions will require less work and allow a more efficient planning.
To prepare for the upcoming deadlines, companies are advised to assess their current situation by following these steps:
For products registered through MRP/DCP:
- Identify all your products with at least one registration by DCP or MRP.
- Identify for these products by when variations, safety updates or renewals are to be expected.
- Check the current format of Module 3 of the dossier i.e. already in eCTD, (partly) in NeeS, paper scans, and CTD format or previous NtA (Notice to Applicants) format.
- For dossiers already completely available in NeeS, the transfer to eCTD is relatively easy and can be done within short time.
- For dossiers available in the old NtA format, the dossier has to be converted to CTD using the NtA-CTD correlation table. The correlation table works well for simple situations e.g. one formulation, one strength. In more complex situations, a critical look needs to be taken at the way information is provided in the dossier and a decision to be made on how to arrange the CTD dossier; Restructuring information in an efficient way avoids unnecessary dossier changes and variations in the future.
- If applicable, harmonization of different dossiers in different countries for the same product can be taken into consideration as well.
- Performing a conversion creates the opportunity to simultaneously make an inventory of possible non-compliances with current standards or internal procedures in the Quality module of the dossier. Although within the baseline submission, no content change is allowed, having such an inventory supports decisions on future updates and applications in new countries.
- Make a priority list of products for which the dossier will need to be converted to eCTD.
- Create a work plan and assess whether you have the tools and resources to conduct the conversions.
For products registered through National Procedures:
- Follow-up on announcements from National Agencies on the implementation of the mandatory use of eCTD in National Procedures on a local level based on the eSubmission Roadmap.
- List all your products registered nationally and follow the steps above, taking into account that the period for transition is one year longer for these products. However, depending on the number of products and possible different dossiers in different EU member states, creating a work plan on time is still advisable.
- Having a work plan, the necessary internal/external resources ready and the required it-tools helps you to implement the eCTD conversion strategy, facilitating a timely implementation and compliance with the regulations. Performing proper planning and processing the eCTD conversion correctly from the start is certainly worth the investment.
Please see http://esubmission.ema.europa.eu/ectd and www.xendo-de.com/en-656/e-submissions.htm for more information.
Or if you have any questions don't hesitate to contact us.
Authors: Patricia Baede, Liesbeth Hoff & Almut Holz