The use of eCTD in new drug submissions

The Electronic Common Technical Document (eCTD) is an interface developed by the International Conference on Harmonization (ICH) to enable the exchange of regulatory data and information from pharmaceutical industries to regulatory agencies. The content is based on the Common Technical Document (CTD) format and follows an eCTD specification (found on the following site: http://estri.ich.org/eCTD/eCTD_Specification_v3_2_2.pdf — the latest updates/notices relating to the eCTD specifications are available on the FDA website).

The CTD holds information in the form of modules, sections, and documents regarding the quality, safety, and efficacy of new pharmaceuticals. This format is used in a marketing authorization application for human use in the European Union, Japan, and the United States (regions that are party to the ICH – International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use). The CTD defines the content of the common modules (modules 2-5), whereas the contents of regional module 1 are defined by each of the ICH regions.

Creating, reviewing, managing the lifecycle of the drug product, and archiving the electronic submission, is simplified by producing the dossier in the eCTD format, while also enabling better review practices by the harmonization of electronic submissions across the regions and modernizing how regulatory processes are carried out.

Evolution of electronic submission:

*eNDA: electronic New Drug Application – Electronic application submitted by drug sponsors to the FDA that proposes approval of a new pharmaceutical for sale and marketing in the US

Formats:

The electronic file should be readable for at least as long as the regulatory process requires, which could be as long as 50 years. The approved formats will continually be updated as technology advances.

Common formats that can be included in an eCTD submission:

• Narrative – pdf
• Structured – XML
• Graphic – where possible, pdf. When not possible, JPEG, PNG, SVG, and GIF.

eCTD is composed of 5 modules:

1. Administrative and prescribing information (regional)
2. Common technical document summaries
3. Quality
4. Non-clinical study reports
5. Clinical study reports

The CTD is organized into five modules. Module 1 is region specific and Modules 2, 3, 4 and 5 are intended to be common for all regions. In July 2003, the CTD became the mandatory format for new drug applications in the EU and Japan, and the strongly recommended format of choice for NDAs (New Drug Application) submitted to the FDA.

EMA are now only accepting submissions which are in the eCTD format. As of January 1, 2008, all electronic submissions must be in eCTD format in the United States, which is facilitated through the FDA Electronic Submissions Gateway (ESG). The Center for Drug Evaluation and Research (CDER — a division of the FDA) receives all NDA submissions and processes on average 20,000 submissions per month across several regulatory programs.

There are clear benefits to using eCTD for new drug submissions — the obvious argument being that less paper makes the whole process a lot faster. (It can take 1 day to obtain a single file from a document room). It also makes it easier to view the dossier as a whole: navigating through the different modules/sections with the use of bookmarks and hyperlinks can be done almost effortlessly in comparison to the paper format. Furthermore, it enables reviewers to instantly identify and review any changes or updates that are required.

As with every process, there are some drawbacks of using eCTD. The software requires trained technical personnel, and it takes time to become familiar with the tool. If a company does not have the right personnel in place, it may be costly to install or the work will need to be outsourced to a vendor which already possesses the infrastructure.

Author: Jill Stevenson - Lead Associate, Regulatory Affairs