All life science companies require approval from Regulatory Health Authorities to place their human, medical device, or veterinary medicinal products on the market. For approval to be granted, the drug application data needs to be submitted in an electronic format, which uses specific software and is structured in the format of an "electronic common technical document" (eCTD). eCTD is a mandatory format set out by the "International Council for Harmonisation" (ICH) supported by regional Regulatory Health Authorities for specific regional requirements.

An ICH agreed data exchange standard for electronic submissions, based on CTD defined content.  eCTD allows for the transfer of files from the sponsor to the regulatory health authority. It contains a directory structure consisting of PDF documents, accessed through the XML backbone, which is an electronic Table of Contents. The PDF documents have bookmarks and hyperlinks to allow ease of navigation between documents, to enable the reviewer to navigate between various documents for the approval process.

Why was eCTD introduced?

eCTD was introduced to harmonize the process between sponsors and regulatory health authorities for the regulatory reviews for drug applications with a common structure.

eCTD enables a global submission strategy that facilitates the use of documents across global health authorities for reviewers to review more efficiently, shortening the time to approval and on to the market.

Historically Submissions were:

  1. Paper dossier submissions that were lengthy and costly
  2. Planning of paper dossiers took longer
  3. Preparing, printing, reviewing, storing and distributing a large volume of documents involved significant costs
  4. Searching paper submission documents was difficult

Principal Driver for Change

Regulatory requirements and mandatory eCTD submissions

Other Drivers

  1. An opportunity to evaluate internal process
  2. Document preparation is easier to prepare as all have been created electronically
  3. Accessing, easier reviewing of historical and global information
  4. Transfer (Agencies, Partners and Due Diligence)
  5. Space-saving is substantial, no archive of paper is required
  6. Submissions are uploaded via an electronic gateway, authorities receive submission instantly,
  7. Reuse of documents for global submissions

The five modules of the eCTD

The eCTD is made up of a total of five different modules,

  1. Information that is specific to each region
  2. Quality, clinical and non-clinical summary documents
  3. Information that relates to quality
  4. References Non-clinical information
  5. References Clinical information

Contents of an eCTD

  • eCTD folder structure/directory structure
  • XML backbone (replaces CTD table of contents)
  • XML backbone containing:
    • application and sequence metadata
    • CTD file titles
    • hyperlink to the files
    • document ID, version
    • document operation
  • Documents in PDF, Microsoft Word, xpt, excel files
  • Checksum values for documents and XML backbone

eCTD Definitions

Contains descriptive metadata and facilitates Lifecycle Management for each file

  • filename and location as well as the files’ relationship to previously submitted information

Document Type Definition (DTD)

  • The DTD defines the acceptable building blocks of an XML document. DTDs are designed and provided by the regulatory agencies to ensure that eCTD submissions are consistent and will be viewable/reviewable using the agency eCTD viewer applications

Leaf

  • A section of the XML backbone containing all of the metadata associated with an individual file that is being submitted, including a link to the physical file

Granularity

  • This term describes the level to which content is broken into multiple files within an eCTD submission. Higher granularity means more, smaller files

Metadata

  • Information that defines information, eg.,
    • Module 1, sequence metadata
    • Modules 2-5 Heading level metadata
    • Leaf elements in Module 1 to 5, document, and file-level metadata

Example of an eCTD folder:

example of eCTD folder

To find out more about eCTD submission and how the expert team at ONIX Life Sciences can help save you time and money then please get in touch with a member of our team by telephone on 01753 257 904 or by email at info@onixls.com