For more information regarding eCTD 4.0, join us for a live webinar on October 22: “Global outlook for eCTD 4.0 adoption: Successes and challenges.” Karl-Heinz-Loebel will present an in-depth update on the accelerating adoption of eCTD 4.0 and key challenges still facing industry.
The second phase of the eCTD 4.0 EU technical pilot is well underway, giving industry, software vendors, and the European Medicines Agency a chance to gain valuable learnings from mock submissions.
While there are some difficulties that still need to be resolved, the eCTD 4.0 technical pilot phase 2 has already provided industry and EMA with an opportunity for hands-on experience with the new format and to consider if there need to be any adaptations. It has allowed the agency to assess differences between the various software vendors and determine what can and can’t be accommodated.
The timeline for completing the second step of the pilot’s second phase is expected to be extended beyond mid-September to allow industry and the agency more time for the submission and evaluation. So far, the pilot covered several scenarios for testing, including1:
- Initial marketing authorization applications with priority given to re-submitting initial eCTD sequences of existing centrally authorized product applications but now converted to eCTD 4.0 format.
- Initial MAA for a duplicate product.
- Validation responses.
- Post-authorization activities.
Initial learnings on the applicants’ side depends on the tool the company is using to compile their eCTDs, but a general outcome seems to be that there are few differences in compiling eCTD 4.0 compared to eCTD 3.2. The challenges are mainly around the identification and assignment of proper keywords, handling of context groups, and priority numbers – all being features that are new in eCTD 4.0 or at least replacing similar functionalities that already existed in eCTD 3.2. Also, some participants assessed the interdependence between the eCTD compilation component and the content management system and saw a need for modifications. Another learning was that besides the actual eCTD compilation and submission process, applicants would need to look into their internal processes of exchanging complete eCTD sequences with external partners, as these processes may also be affected by the new format.
The next step of the pilot will consider more complex scenarios and put more focus on forward compatibility (continuing eCTD lifecycle for existing eCTD 3.2 dossiers in eCTD 4.0), grouped submissions, and probably the lifecycle of keywords.
EMA documentation updated
EMA has also updated the documentation for applicants, the validation criteria for eCTD 4.0 submissions, and EU eCTD 4.0 controlled vocabularies. The criteria are important to show industry what EMA will be checking when they receive a submission to determine whether or not it is technically valid. It should be noted that the current validation criteria are not yet final, and further updates will need to be released.
The controlled vocabularies (CVs) initially released by EMA were incomplete but updated shortly after the missing elements had been detected. This also provided applicants with some insight on EMA’s process of updating CVs and how long it takes vendors to implement them.
EMA has yet to update the draft implementation package from October 2024. However, with experience gained from the second phase of the pilot, the agency is likely to issue a further update, and perhaps even the final version, within the next few months.
For most tool vendors, it seems everything is in place to enable their clients to build eCTD 4.0 applications for Europe, though the pilot submissions have revealed some minor glitches in some tools that still need to be fixed.
Moving forward with eCTD 4.0
The progress of the pilot makes it more likely that we might see the first real eCTD 4.0 applications being submitted in Europe before the end of this year, and the planned mandatory use of eCTD 4.0 for Centralised Procedure Applications in 2027 is an achievable target.
With the US Food and Drug Administration (FDA), Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), EMA, and most likely some other agencies being able to receive and assess applications in the new format, the onus will be on global applicants to increase their efforts to implement eCTD 4.0 as their preferred submission format and exploit the synergies of using the same format in their major markets.
Note: All references in this article are from the EMA’s eSubmission eCTD4.0 webpage at https://esubmission.ema.europa.eu/eCTD%20NMV/eCTD.html.
About the author:
Karl-Heinz Loebel is Director and Principal Consultant, Regulatory Operations, at PharmaLex. With more than 20 years of experience in regulatory operations, Karl-Heinz has built his expertise in data management and the electronic exchange of information with regulators and has been a constant contributor to shared industry/agency forums on digital data exchange for the past decade.
