eCTD Publishing: 10 Tips for a Smooth Submission Process

Over the past few decades, the pharmaceutical industry has seen a dramatic shift in how regulatory submissions are handled. Gone are the days of bulky paper dossiers and late-night CD-burning sessions — electronic submissions are now the global standard. As the pace of digital transformation continues, keeping up with technical requirements and best practices for eCTD (electronic Common Technical Document) publishing has become increasingly important. 

This blog offers a quick overview of how eCTD works, followed by 10 practical tips we’ve learned from hands-on experience. Whether you’re preparing your first sequence or looking to streamline your process, these insights can help you avoid common pitfalls and meet your submission deadlines with confidence. 

History of eCTD Development  

The Common Technical Document (CTD) format was developed by the International Council for Harmonisation (ICH) Multidisciplinary Group 4 Expert Working Group (ICH M4 EWG). The initial release for public consultation at step 2 of the ICH adoption process occurred in November 2000, prior to implementation at step 5 in 2002.  

It has since been defined as an ICH standard, similar to MedDRA and ESTRI. This new dossier structure, comprising five modules, replaced the previous Part I and Part II formats and by 2003 had been adopted as mandatory or ‘strongly recommended’ for new applications in the EU, US and Japan.  

The CTD format was further developed by ICH into an electronic format, or eCTD. The ICH M2 EWG was responsible for developing the initial specifications to further streamline and standardise the submission of regulatory information across different regions.  

By the end of 2002, version 3 of the specifications had been finalised with broad uptake by regulatory agencies. Version 3.2.2 became the most current version, reaching step 4 of the ICH adoption process in 2008, and it is now the widely accepted global submission format.  

How do eCTD submissions work?  

Essentially, eCTD facilitates the submission of PDF documents organised in the CTD format and structure. Each submission or sequence uses the markup language XML, similar in nature to HTML, to provide a navigable file system that can be viewed in a web browser.   

A mathematical algorithm – the MD5 checksum – is generated for each submission and is unique to the eCTD contents. Generation of the MD5 checksum is a standard operation that can be calculated with software used by both the sender and recipient of the eCTD sequence to confirm data integrity.   

eCTD global adoption & version 4  

Since 2002, eCTD has gradually been adopted as the primary means of submission and is now mandatory in all major regions. Although there has been little change in the technical specification at an ICH level since 2008, regional requirements for Module 1 have undergone regular minor updates.  

The development of version 4.0 began with the formation of the ICH M8 EWG/IWG in November 2010. This version aimed to address the evolving needs of the industry and regulatory authorities.  

The ICH Assembly endorsed the Step 4 ICH eCTD v4.0 Implementation Package in December 2015, and there have been further refinements to supporting information, with eCTD v4.0 Implementation Guide (v1.6) and Controlled Vocabulary Package (v1.0) endorsed by ICH in May 2024.  

It is expected that eCTD 4.0 will be adopted globally over the next few years, and a future blog post will cover the key changes and improvements expected with the implementation of the new standard.  

The eCTD has become the de facto standard for regulatory submissions in the pharmaceutical industry, facilitating a more efficient and harmonized process for submitting and reviewing regulatory information globally.  

10 Tips for effective eCTD publishing