The eCTD (electronic Common Technical Document) is the standard format the pharmaceutical industry uses to submit regulatory information to agencies worldwide. For the last 20 years, the eCTD has provided the structure to facilitate the review of pharmaceutical products through all phases of drug development. The introduction of electronic submissions parted ways with the days of Regulatory Operations staff standing in front of a copier and hand paginating, in triplicate and the seemingly endless volumes of paper. The eCTD brought forth the concepts of lifecycle management, document reuse, study tagging files, and the importance of metadata. We look forward to the global implementation of eCTD 4.0, which will represent another step forward in regulatory submissions.
While articles are available on this topic, this post will introduce new concepts and benefits that will replace or enhance electronic submissions as we transition from eCTD version 3.2.2 to 4.0.
Submission Units
The implementation of eCTD 3.2.2 harmonized the granularity of documents organized in Module 2 through Module 5. In Module 1, the implementation of regional information was delegated to individual countries, allowing them to determine the hierarchy and required metadata. The current situation resulted in multiple XML files and style sheets contained within each eCTD sequence. Finally, eCTD 4.0 will introduce one XML file that covers regional and ICH modules. The Submission Unit will create more flexibility by increasing the granularity of regulatory submissions. Companies will have the capability to establish smaller, more logical groupings of documents that can be independently managed.
Context of Use
In eCTD 4.0, we will see the introduction of Context of Use and Keywords. These additions will help sort and organize how regulatory reviewers interpret information within a specific submission. The Context of Use in Module 4 and Module 5 will replace the STF (study tagging file) when organizing a collection of study-specific documents. Context of Use groupings go beyond simply organizing documents into study specific groupings. Individual documents will include metadata that will clarify to regulatory reviewers why a document should be reviewed and its role in the submission. The Context of Use groupings will affect the familiar lifecycle management we now utilize in eCTD v3.2.2. The lifecycle operators of “New,” “Replace,” “Delete,” and “Append” are currently in a 1:1 relationship. As we advance, our lifecycle operators will be “Active,” “Replace,” and “Suspend” and will allow many documents to replace a single document or one document to replace many. eCTD v4.0 will no longer include the “Append” lifecycle operator.
Document Reuse
The concept of document reuse is already familiar to regulatory teams, especially regarding how they currently submit data within their eCTD applications. Documents submitted in one dossier may be placed in another dossier (e.g., IND to NDA, MAA to BLA). Reusing documents through the various global waves of submissions is a great benefit. Still, a regulatory publisher must digitally duplicate the document to share across multiple stand-alone regulatory filings. In eCTD 4.0, each document will be assigned a unique identifier. Unique document identification will allow the reuse of documents across applications without physically submitting the document multiple times.
The transition from eCTD version 3.2.2 to 4.0 marks a significant advancement in regulatory submissions within the pharmaceutical industry. eCTD 4.0 introduces several innovative concepts and improvements, such as a unified XML file for regional and ICH modules, the Context of Use, enhanced lifecycle management, and document reuse with unique identifiers. These changes will streamline the submission process, improve review efficiency, and ultimately benefit sponsors, health authorities, and patients. As we move forward with global implementation, the enhanced eCTD 4.0 framework promises a more efficient and flexible approach to regulatory submissions, further supporting the development and approval of innovative therapies.
With our deep expertise and commitment to innovation, Syner-G’s Regulatory Operations team is ready to guide you through the transition to eCTD 4.0, ensuring seamless submissions and successful regulatory outcomes.
