The Electronic Common Technical Document (eCTD) is the standard format for submitting applications, amendments, supplements, and reports to the U.S. Food & Drug Administration (FDA). The eCTD harmonizes the regulatory review process for global drug development, as its structure is based on the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines.
In addition to streamlining the review process for the FDA, the eCTD format also simplifies the submission process for sponsors, as it is the same format used by regulatory agencies in other countries. However, failure to comply with the regulatory and technical requirements could jeopardize the success of your submission and your product development plan as a whole, especially for early-stage biotechs working with limited resources. Here are strategies for avoiding some of the most common electronic publishing pitfalls on the path to submission.
Have the right people, processes, and technology in place
The transition to a fully digital submission process requires coordination across many functional areas. While an eCTD can be built manually, this is a long and tedious process. There are many integrated document management and publishing software solutions that can be used to automate the process. However, technical expertise and extreme attention to detail are still essential. For instance, if you choose to use either eCTD publishing software or viewing software, you should include time in your submission timeline for selection, setup, validation, compatibility checks, training, and maintenance, or partner with a regulatory services provider who can help you make the best decision for your needs.
Perhaps most importantly, successful eCTD submissions require knowledge and understanding of the current eCTD Submission Standards, which is updated periodically, and other local and global regulations and requirements.
Familiarize yourself with the current technical requirements
eCTD submission requires strict compliance with the Comprehensive Table of Contents Headings and Hierarchy and eCTD Submission Standards Catalog, as well as very detailed technical requirements. These technical requirements range from formatting specifications and hyperlinking to metadata requirements and folder and file naming conventions. The FDA uses a commercial off-the-shelf product to validate eCTD submissions according to their published specifications for eCTD Validation Criteria.
According to the FDA, the top reasons that eCTD submissions get rejected include:1
- Duplicate sequence submission received
- Mismatch between the application number in the us-regional.xml and the application number on the FDA form
- Submission sent to the wrong Center
- Corrupted or broken media received
- Submission was not submitted in standard eCTD format
Develop templates or guidelines on how to format, write, and prepare documents for submission.
This helps ensure a more cohesive application, and may help limit the time required for publishing documents in eCTD format. An experienced regulatory services partner will already have templates and guidelines in place for your use, which saves the time and costs involved with developing these yourself.
Ensure that your timeline for submission allows for sufficient time, creating technically compliant eCTD documents.
Last-minute content changes in final documents can have a ripple effect on the entire submission, and lead to delays. Using an integrated document management and publishing software can be especially valuable here. Most eSubmission management software solutions also include validating systems that will identify validation errors, further minimizing the risk of submission rejections.
To learn more about eCTD submissions and the requirements for technical conformance, refer to Guidance for Industry: Providing Regulatory Submissions in Electronic Format –Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications, which was revised in February 2020, and the eCTD Technical Conformance Guide, which was last updated in December 2019.
Regulatory Professionals, A Division of Premier Research, has been a trusted eCTD vendor for small to mid-size pharmaceutical, biopharmaceutical, and medical device companies since 1995. Click here to learn more about our services and get in touch with our electronic publishing team.
[1] U.S. Food and Drug Administration. FDA eCTD Overview and Submission WBT Validating eCTD Submissions. Available at https://www.accessdata.fda.gov/cder/eCTD/validate/validate/fd_06_01_0040.htm.