The US Food and Drug Administration (FDA) has set May 5, 2018 as the compliance date for submitting many types of files—Drug Master File (DMFs) and commercial investigational new drugs (INDs)—in the electronic Common Technical Document (eCTD) format. A DMF provides confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs. The agency has extended the compliance date for submitting Type III DMFs in the eCTD format by one year to May 5, 2019. Other eCTD deadlines, however, have not changed. And files not submitted in eCTD after this date will be rejected.
Are you ready to meet this deadline? Or do you have lingering concerns about how to implement this technological change in your organization? In this blog, I’ll discuss what eCTD is and the business process changes you’ll need to make to create submissions in this format.
eCTD: What it is and why you should use it
The eCTD format is the standard for submitting applications, amendments, supplements, and reports to the FDA’s Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER). An eCTD submission is comprised of five modules: region-specific information, summary documents, quality-related information, non-clinical study reports, and clinical study reports.
Using this format is beneficial to both sponsors and regulators. When materials are submitted electronically, it is easier for the FDA to review data, approve new drugs, and monitor drugs after they go on the market. Using eCTD also simplifies the process for sponsors because it’s the same format used by regulatory agencies in other countries.
What submission types does the FDA require in the eCTD format?
- Commercial IND applications (for products that are intended to be distributed commercially)
- New Drug Applications (NDAs)
- Abbreviated New Drug Applications (ANDAs)
- Biologics License Applications (BLAs)
- All subsequent submissions to these types of applications, including amendments, supplements, and reports, even if the original submission was filed before the requirements went into effect
- Master files (MFs), such as DMFs, which are considered to be submissions to an IND, NDA, ANDA, or BLA
You must implement three main business process changes to submit in eCTD format.
Submission tracking, planning, and delivery
To ensure meeting the company’s submission target date, you need to track all submission components, their due dates, and content owners. This planning document should be updated regularly to keep a clear vision of submission priorities.
Assembling eCTD submissions requires more time than assembling paper submissions. You can still meet aggressive submission dates if documents are provided for eCTD processing on a rolling basis. Plan to finalize and approve documents based on when the data is available as opposed to working backwards from the target submission date. Once documents are approved, they should be sent for eCTD processing. The fewer files left for processing nearing the target submission date, the faster eCTD compilation activities will be completed, and the probability of hitting the company’s target date (or beating it) will increase dramatically.
What does being “submission-ready” mean?
Generating submission-ready PDFs starts with documents based on standardized Microsoft Word content templates. Using templates helps writers generate documents that meet content and granularity requirements and are technically sound for publishing (generating bookmarks and hyperlinks). Consistent use of Word styles and accurate cross-referencing techniques are essential for generating submission-ready documents.
A “submission-ready” document is a complete, data quality controlled (QC’d), content-approved, properly formatted, text-based document that has been rendered to PDF. Submission-ready documents should also adhere to eCTD granularity requirements.
Legacy reports often require custom PDF-level processing. Non-standard clinical and non-clinical reports will require more intensive processing than files written using content templates. The key is consistency. All files, regardless of their origin, should meet the same publishing standards.
eCTD review, publishing QC, and validation prior to submission
After all submission-ready files have been transferred and fully processed, perform a quality review of the eCTD prior to submission. The quality review should ensure all documents are present, any content updates have been incorporated, and the publishing is adequate and correct. Leaf titles should also be reviewed to ensure they are descriptive and take into account the eCTD lifecycle implications over time. Lastly, the complete submission should be validated to ensure an error-free technical validation report and technical acceptance upon receipt at the FDA.
The days of paper applications are numbered. If you haven’t made the switch to eCTD, it’s time to take action. Whether your company prepares eCTD submissions in-house or plans to outsource them, your solutions must be in place.
Planning, drafting, reviewing, and editing regulatory documents needed for the submission dossier is a pre-requisite to submission publishing. But, drug development teams often find submission planning to be a real challenge. To learn more about best practices for a submission development, please watch this webinar.