Lifecycle management is an important component of any regulatory submission strategy. Not only is this process used to keep electronic common technical document (eCTD) applications up to date, but it’s also the most efficient way to submit document changes and ensure the health authority has quick access to all the most current documents and related information for an application in one place.
Understanding lifecycle management best practices can help sponsors streamline the submission process, avoid future rework and reduce confusion caused by duplicate documents. I’ve supported thousands of eCTD sequences over the past decade and below is a high-level overview of basics and best practices that all sponsors need to know.
- Keep only the most current information in the current view of the eCTD: Every eCTD includes a current view—used by health authority reviewers to access the most current, up-to-date files related to an application—and a cumulative view—which includes a view of the entire application, including content that has already been appended, deleted or replaced. To make the document review process as convenient as possible for the health authority, it’s critical to utilize lifecycle management appropriately to keep only the most current, up-to-date information in the current view of the eCTD.
- Understand “operation attributes and when to use them: Every eCTD contains an “XML backbone,” which effectively serves as the Table of Contents for the submission. The XML backbone should include document-level metadata that identifies the operation attribute of each document. Understanding these attributes is absolutely critical to effective lifecycle management.
- New: A document is classified as “new” only when it has never been submitted in the current eCTD, or when converting from a paper-based submission to eCTD format.
- Replace: A document is classified as “replace” when it is completely replacing a previously submitted document in an eCTD. Prior versions of replaced documents are still available in the cumulative view of the submission, but are replaced in the current view.
- Delete: In contrast, a document is classified as “delete” if it is intended to be completely deleted from the eCTD current view. This classification is used to make corrections or to remove content from current view, without replacing it.
- Append: A document is classified as “append” when information is added to a previously submitted document. However, this is only to used for study tagging files, and is not recommended for authored documents.
- Certain sections of an eCTD also require specific metadata. For example, an eCTD’s Module 1 – Administrative section must include company and technical contacts, the DUNS number and other application information. Additional metadata is required for promotional materials in this module. For most metadata, if changes are needed after submission, these sections need to be deleted and submitted as “new,” with the updated metadata. It’s important for sponsors to be familiar with the specific metadata required in each module.
- When it comes to eCTD submissions, granularity is usually the best policy. Be as detailed as possible when preparing documents to save time when filing future maintenance submissions.
- When authoring documents, think strategically about lifecycle management. Determine specifics up front. For example, determine whether attachments or supporting documents (such as Certificates of Analysis (COAs), Method Validation reports, etc.) will be included in the XML backbone and hyperlinked. If so, they need to be prepared as separate documents so future submissions can replace or delete the files as needed. Specifics such as this need to be thoughtfully planned in advance when building the initial submission to ensure future submissions are as efficient as possible for sponsors to create and for regulators to review.
- A submission tracker is a priceless lifecycle management tool. A submission tracker can be as simple as an Excel file, as long as it outlines all content contained in a submission, the date it was received, the date it was processed, the date it was checked by quality control and other details. It serves as a guide to everything that’s included in an eCTD, and as a checklist to make sure all necessary steps have been completed and nothing is overlooked.
Even after your product earns regulatory approval, the compliance journey continues. Sponsors and regulatory submission authors should be familiar with the basics and best practices of lifecycle management up front so they can avoid costly delays and inefficiencies throughout the full lifecycle of their products.