electronic Common Technical Document (eCTD) v4.0 Overview

For almost 20 years, eCTD has been around, and we have seen how it has changed the world of regulatory submission. A change from version 3.2.2 of eCTD to version 4.0 of eCTD will be the next big evolution of electronic submissions. At its core, eCTD v4.0 is a shift in format that provides users with access to new capabilities. The upgrade to eCTD v4.0 would carry several major changes. Changes such as providing a single XML message instead of a regional one and an ICH one, a hierarchy more representative of the business process of submission, and a much more sophisticated life-cycle management than what can be done today. The eCTD v4.0 ability to be a bi-directional communications network between submitters and health authorities is the most drastic shift.

The story of the electronic Common Technical Document, also known as eCTD, began in 2003 with the clear objective of establishing a worldwide standard for electronic submissions. Fifteen years later, eCTD has been turned into the standard norm for industry-wide submissions around the world. A lot has changed over the past decade and a half, in the way that electronic submissions are assembled and filed, and many of these changes and recommendations are formalised by eCTD v4.0.

In particular, eCTD v4.0 is a format change aimed at substantially streamlining the analysis of electronic regulatory dossiers, allowing content to be reused, and enhancing cooperation between sponsors and regulatory authorities.

The upcoming next major version (NMV) of the electronic submission format is version 4.0 of the electronic Common Technical Document (eCTD). More than 15 years ago, the initial version of eCTD was created by ICH. A single standard was provided for electronic data transmission and allowed industry in order to interact and share information consistently with regulators.

The eCTD v4.0 is based on HL7 – Health Level Seven standard called RPS. Compared to eCTD, the RPS standard was intended for broader use across industries and goes beyond the original scope of the life sciences sector. Looking forward it is envisaged that it will also support submissions for things such as medical devices, veterinary and other regulated products.

The main purpose of the new eCTD standard is to make it easier for sponsors and regulators to process and review electronic submissions, as well as to encourage better re-use of content. It does this by the implementation of:

• Bi-directional interaction: Sponsors can only submit an eCTD series to an entity at present. As an eCTD series, eCTD v4.0 implements two-way communication that allows agencies to send correspondence to a sponsor, such as a request for information. The US FDA has already announced in its regional implementation guide that it plans to include two-way communication.
• Re-use of Document: When compiling a marketing application, the work of regulatory operations practitioners would be greatly simplified by the opportunity to refer to files in an investigative application. Now, eCTD v4.0 facilitates the re-use of document files. A unique ID that can be referenced as long as it is in an Agency’s system is now allocated to each text.
• Controlled vocabularies: One of the critical components of eCTD v4.0 is managed vocabulary, which essentially allows simple, unambiguous communication between systems that send and receive XML messages. Multiple bodies will regulate regulated vocabulary: ICH, regional authorities such as the FDA and other third-party designated bodies.
• A new XML schema designed to enhance robustness, flexibility, and the reliability of the messaging system over the long term.
• Collaboration with different Standards Development Organizations (SDOs): Another aim was to establish the new norm and not inside the ICH alone, but in partnership with numerous SDOs). Therefore, eCTD v4.0 was developed. Together with a project for the HL7 Regulated Product Submission (RPS). As an ISO standard, the final release will be published. The goal for industry and regulators is to establish a much closer relationship between eCTD dossiers and structured data directories (set out in the ISO IDMP). This opens up an opportunity for multiple synergies, including successful regulatory review, a finer granularity for faster decision-making, and a pragmatic commitment to the safety of patients.

Document Re-use with Universal Unique Identifier (UUID): There is currently no easy way of recognising a document submitted previously. It is not usual for the same document to be submitted over and over again. This has been a long challenge and by adding a document tagging capability, eCTD v4.0 gets rid of this repetitiveness. This assigns a document a unique identifier that can be used as a reference in cases where a document must be reused for different sequences in the same application. Referenced documentation may have various metadata or may be found in the section of the different table of contents. A Universal is called a unique identifier UUID. This is a number generated by a machine, based on an algorithm. When a document is submitted and maintained by a regulatory authority, it can in any subsequent submission, be referenced by its unique identifier.

Enhanced Life Cycle Control: The need for more versatility in handling submissions is recognised by eCTD v4.0 over a period of time.  The new standard enables more papers to be registered, substitute one, or substitute many for one text. With the introduction of eCTD 4.0.0, the append lifecycle operator, built as a way for applicants to upgrade the content already submitted, is scheduled for official elimination.

Metadata Corrections: In eCTD v4.0.0, metadata will play an important role. It will use keywords to similar details in the group, such as a product, and the context of use allude to heading for the CTD, such as references. The ease would also boost the with which to correct inaccurate metadata entries. Current edition of the eCTD is very small-a single typo might end up creating separate eCTD sections, and the entry cannot be updated if submitted.

Table of Contents, Tagging Files for Analysis & Use Context: As compared to eCTD v3.2.2, the Table of Contents (TOC) or hierarchy in eCTD 4.0 is not defined. To identify all files associated with a document, Study Tagging Files (STFs) have been created to study for Modules 4 and 5. STFs are required in the United States and are not required in Europe and are not approved in Japan. The role of STFs in eCTD v4.0 falls to Document Groups. A victory for global harmonisation is the removal of the STF. Context of Usage is similar to a leaf and defines the document type. The code for each Context of Use defines where, when providing a reviewable structure, documents should be inserted into the CTD / eCTD TOC.

Eventually, eCTD v4.0 will become the compulsory standard for electronic submissions. The analysis of electronic regulatory applications and coordination between sponsors and regulators will not only be simplified, but also with other third parties, such as CROs or licencing partners.

• Streamline the review of electronic regulatory dossiers
• Reusable content
• Better document management
• Metadata corrections
• Better life-cycle capabilities
• Increased Harmonization

cCTD v4.0 is going to revolutionise electronic submissions, but its broad advantages are undoubtedly, for manufacturers, vendors, and companies alike, it would outweigh the obstacles. There will be a time when all versions of the norm are in service, but there is an imminent transition. The team at Celegence is committed to ensuring that our services are compatible with the potential needs of life science organisations in order to overcome these challenges.

Automation of eCTD

Automation can help in auto-publishing, auto-QC checks, Compliance reviews, and more. The Publishing will become more automated, starting with robotic process automation (RPA) and leading to cognitive automation and artificial intelligence.

Automation can save more time to clients. The process of publishing will be faster and more accurate with help of the RPA. With the new requirements and new technology, we can help our clients better.