Publishing

In order to ensure efficient preparation and review of the many regulatory documents that are transmitted within applications to health authorities, standardisation is required for writing and publishing.

The Common Technical Document (CTD) describes the required format and organisation of a Marketing Authorisation Application (MAA) dossier for a medicinal product for human use in the EU. CTD in electronic format, known as eCTD, became mandatory in the EU for Centralised Procedures in 2010 and all other procedures (MRP, DCP and national) as of 2018/2019. It is now the required submission format for all types of regulatory activities in the EU, covering initial MAAs, variations, renewals, PSURs and ASMFs.
Prior to the mandatory use of eCTD, the Non-eCTD electronic Submissions (NeeS) format was accepted as a transitional format (and is still accepted in specific cases). While it is possible to generate NeeS sequences without a specific software, a specific publishing software is required to generate eCTD sequences.
In eCTD format, all documents are accessible via an electronic Table of Contents (the so-called xml backbone) and integrity of the files is ensured by an MD-5 checksum that is generated upon export.

An advantage of the eCTD format is that it enables the viewing of sequences together to gain a consolidated view of the current dossier status, considering that during the eCTD lifecycle, documents may be added, replaced or deleted, e.g. with variations or response submissions. When switching from NeeS or paper format to eCTD, the submission of an eCTD baseline sequence (at least for the Module 3, the quality-part of the dossier, which is frequently subject to variations) is therefore highly recommended.
For the preparation of eCTD sequences, the required documents for the submission should be correctly formatted considering current eCTD Specifications and guidances.

Headings should follow a hierarchical structure and internal links to sections, tables and figures need to be set up and checked that they function correctly. Documents of multiple pages should have an electronic table of contents and bookmarks to aid navigation. PDF files need to be formatted to open with the bookmark panel view, bookmarks and links should be set to inherit zoom. Text (especially of scanned reports) should be processed to be electronically searchable and PDF files should be reduced in size and have fast web view activated. Within the eCTD sequence, relevant external hyperlinks should be created between the documents to facilitate review and navigation by the assessor.

Details on the individual submission are provided as metadata within an eCTD envelope in the regional Module 1, which facilitates processing of eCTD sequences by regulatory authorities.

Within an eCTD sequence, only PDF files are allowed in a defined structure and meaningful filenames should be given, considering file naming conventions where necessary. If word documents are to be submitted as part of the application, these should be placed in a working-documents folder outside of the eCTD sequence.

Prior to submission, eCTD sequences need to be technically validated against the latest validation criteria.
Technical validation checks the submission for technical errors such as broken links and ensures compliance with eCTD Specifications, such as file naming conventions. Only technically valid eCTD sequences can be successfully imported and processed by regulatory authorities.