In helping clients with their regulatory operations and electronic publishing needs, I’m often asked about preparing regulatory submissions in the electronic common technical document (eCTD) format. While a lot of us have been working in the eCTD format for many years, new start-up companies focusing on rare diseases and new technologies to treat patients are often surprised by the regulatory hurdles that eCTD presents. In this blog post, I’ll share answers to some of the most common questions from these clients.
Q： What is the process for getting a submission into the eCTD format and when should we start?
A： The submission of a marketing application is seen as a key milestone in a long development process. People unfamiliar with the regulations, specifically eCTD requirements, can be caught off guard as their NDA submission date approaches. The NDA medical writers and Regulatory Affairs leads have not prepared their documents for the eCTD publishing stage and now they realize that documents need to be rewritten to match eCTD granularity and hyperlinking requirements. So, let’s first take a high level look at the eCTD which contains 5 modules:
- Administrative information and prescribing information
- Common technical document summaries
- Non-clinical study reports
- Clinical study reports
The first step is to get your submission documentation into the format specified by eCTD templates. Regulatory and Medical writing teams usually write all the clinical and non-clinical studies in content templates that format everything according to eCTD regulations. These eCTD authoring templates should be used for any report planned for a regulatory filing no matter how far off the submission may be.
Once the documentation is in the correct format, the content should be approved by subject matter experts as well as regulatory operations. Once approved, it’s transferred to the publishing team who starts the submission compilation. This involves creating PDF files, adding navigation aids (bookmarks and hypertext links), and uploading it to the online eCTD publishing software. Once the publishing team has performed their process, the eCTD files and sections should be reviewed again by the subject matter experts.
Modular Structure of Common Technical Document
Q： What’s the XML backbone and how do we create it?
A： The publishing software completes two major tasks automatically. First, it creates the proper folder and subfolder structure that organizes the eCTD documents by modules. It also auto-generates an XML backbone.
The XML allows the eCTD viewing software to load the application and structure the files in their proper order over the life-cycle. The XML backbone provides required metadata as well as document life-cycle operators which are loaded into the eCTD viewing tool.
Without an XML backbone, your submission will fail the regulatory agency’s validation software. Thus, the health agency reviewers will not review your submission because it won’t load into the review software.
Q：What do people mean when they refer to the “metadata” of a submission?
A： Metadata in the case of eCTD submissions refers to structured data.
Think about unstructured data as a PDF file or a Word document. Large submissions contain thousands of documents with unstructured data.
The eCTD message that is sent contains structured data as well. Some of the information that is entered as metadata with submissions includes the application types, sequence types, sequence numbers, Dun & Bradstreet Number, the regulatory contact name, and their phone number. The regulatory operations will add this information through the eCTD publishing software.
The role of metadata will likely be expanded with future versions of eCTD as eCTD V4 is implemented and potentially impacts identification of medicinal products (IDMP) on Structured Product Labeling (SPL).
I hope that you now know more about the structure of an eCTD submission. In an upcoming blog post, I’ll discuss common pitfalls sponsors encounter in the drug submission process and some best practices for addressing them.
To learn more about how the FDA uses eCTD as part of its review process, please read a white paper that we’ve written on this topic. Let me know what you think in the comments section!