ICH’s eCTD Version 4.0
The Electronic Common Technical Document (eCTD) has become the global standard for electronic submissions in the Life Sciences industry. An eCTD submission has five modules:
- Region-specific information
- Summary documents
- Quality-related information
- Nonclinical study reports, and
- Clinical study reports.
Most global regulatory agencies such as US FDA (USA), EMA (EU), Health Canada (Canada), TGA (Australia), Japan’s MHLW, and few other health authorities have mandated eCTD for regulatory submissions making it a globally accepted submission format.
Developed based on Regulatory Product Submissions (RPG) standard (a Health Level Seven standard – HL7), eCTD was harmonized for regulatory purposes with regular guidance from International Council for Harmonization through various versions. eCTD’s fourth and current version has been formally published with various updates that are aimed to simplify the process for both regulatory agencies and sponsors. Eventually version 4.0 will become the mandatory format replacing version 3.2.2 which is currently in active implementation thus making it relevant for sponsors to remain in the know about the changes.
Let us delve deep to understand what changes should the sponsors look out for in the latest version and whether these changes will prove advantageous or pose challenges!
Objectives of eCTD V 4.0, and Relevant Updates/ Additions/ Eliminations
- Bidirectional Communication – Of all the changes of eCTD Version 4.0, this could be the one with the highest impact. This was reflected in the initial form of this version. But in its most recent revision, the ICH has refrained from commenting on this. Nevertheless, regulatory agencies are making simpler changes that are headed in this direction.
- Document Re-usability with Universal Unique Identifier (UUDID) – Sponsors end up submitting multiple times as regulatory agencies request more information upon review. While compiling a new marketing authorization application (MAA), the UUID (assigned to all submitted documents) lets applicants refer to investigational application instead of creating them from ground up in the MAA.
- Controlled Vocabulary – Communications often contain words that could mean different due to perspective and usage. To check that the message is clear and unambiguous, controlled vocabulary has been implemented in eCTD version 4.0. Along with ICH, various regulatory bodies and some designated third-party organizations will have governing control over this vocabulary.
- Simplifying XML Backbone Structure – Intended to reduce the complexity of the XML schema that forms the basis for eCTD, the new version is intended to gradually introduce updates that will make it robust and flexible. One such change can be noticed in the US FDA’s latest revision of version 4.0 where they have made changes that could replace the XML backbone with a more dynamic message structure. This permits the submission of only the headings relevant to the sequence instead of the entire sequence.
- Working with Various Standards Development Organizations (SDOs) – The ICH has often relied on internal expertise to devise the standards for developing/ editing eCTD structure. Foreseeing global need for dynamism, the Council has worked closely with HL7 RPS while working on the latest version. In its final release, the version will be published as an ISO standard paving way for cooperation between industries and regulators.
- Other Additions and Eliminations: ‘Context of Use’ and ‘Document Groups’ functions have been included in the new version. ‘Append lifecycle operator’ function used for editing submitted documents will be eliminated in eCTD V 4.0. Additionally, this version allows changes to keyword definition display name values without resubmitting the corresponding physical files. The Study Tagging Files (STF) used to identify files in Module 4 and 5 have been removed. Similarly keywords can now be used to group similar information.
Advantages Resulting from the Version Change
- Bidirectional communication will significantly lower the review timelines as regulators will be able to closely coordinate with the sponsors to request information from time to time and reduce the deficiencies for the sponsors. If the communication channel is streamlined as published in original objectives, it has the potential to decrease the number of formal communication exchanges between sponsor and reviewer.
- Often the same support documents used in investigational application are repeatedly submitted to the health authorities in marketing authorization application for review. Using UUID to refer to those documents from investigational application might reduce the cycles of work for the applicants. Documents can be easily procured simply by referring to the tagged ID once they have been allocated an UUID by the regulatory agency. This also simplifies the dossier structure by limiting the number of documents to be attached within.
- Removal of Append lifecycle operations along with introduction of functions for replacing multiple documents with one documents and vice versa are aimed at bringing enhanced lifecycle control by offering more flexibility to manage submission content in the years after submission.
- Removal of STFs has brought about global harmonization as many of the regulatory agencies have not been accepting it or made it optional. Changes pertaining to Use of Context and Document Groups have been brought in to enhance document management. Similarly Keyword grouping will prove useful for metadata corrections.
Challenges to Look Out
While changes will be published as revisions to document, once the implementation begins, regulatory bodies might take either a phased approach or one-time implementation. Either way, sponsors would have to track the revisions and the impact these changes could have on their submissions. Furthermore, many of the changes to the document might prove technically elusive for sponsors which can have impact on business timelines as well. Applications that are being compiled for future submission must be reviewed internally as the time to edit could be limited when the new version changes are mandated.
When including UUID for referencing documents, sponsors might also want to liaison with the agency to understand the technicalities associated with the process. Similarly, they would need professional assistance to use new functions. With more changes being planned for impending release in future versions, an end-to-end overhaul of regulatory affairs, regulatory operations and CMC might also be necessary.
Overcome Challenges with Techsol Expertise
With both product and service expertise pertaining to eCTD, Techsol is well-positioned to serve the evolving needs of sponsors aiming for marketing authorization approvals in global markets. Our regulatory operations and regulatory affairs experts have proven expertise of compliant submissions and years of domain experience. They can assist you during compiling and thus ensure regulatory compliance throughout the lifecycle of the products being marketed.
Should you have any doubts about the latest versions and want to understand the resulting impact, you can contact us by mailing at firstname.lastname@example.org.
• International Council for Harmonization, Oct 2018 ‘Support Documentation for M8: eCTD EWG eCTD v4.0 Implementation Package v1.3’
• United States Food and Drug Administration, Jan 2021 ‘eCTD Technical Conformance Guide’
• European Medicines Agency, April 2016 ‘Harmonised Technical Guidance for eCTD Submissions in the EU’x