Editor’s Note: Jason Rock served as Project Lead for the HL7 RCRIM Expert Working Group that developed the Regulated Product Submissions (RPS) standard. This post is the second in a series on the Next Major Version (NMV) of eCTD, eCTD v4.0, which is based on the RPS standard.
The focal points of eCTD v4.0 like document reuse, enhanced lifecycle control and more liberal use of metadata, and the ability to alter that metadata if errors are made, are countermeasures to the limitations of eCTD v3.2.2. Overall, these enhancements represent common sense solutions that give regulatory professionals a more efficient way of doing business.
Documents submitted as part of investigational applications (INDs and CTAs) very often carry over to the marketing application. As of now, there is no straightforward way to acknowledge that a document was previously submitted. It’s possible that the same document must be submitted over and over again. Document reuse in eCTD v4.0 gets rid of this repetitiveness.
A document is tagged with a unique identifier that can be referenced should a sponsor want to use that document again in the same sequence or in a different application. The referred document can also have different metadata or be located in a different table of contents section.
This unique identifier is call a Universal Unique Identifier (UUID). It’s a computer generated number, based on an algorithm, that all but guarantees two people will not generate the same number. If you generated 1 billion UUIDs every second for the next 100 years, there’s only a 50% chance that you’d create a duplicate identifier.
Once a document is submitted and retained by a regulatory authority, it can now be referenced by its unique identifier in future submissions. Other have suggested using the same UUID across multiple regulators. Although that is possible, it goes against the spirit of the UUID. The UUID should be system generated and used only once, otherwise you run the risk of using the identifier when you should not.
Enhanced Lifecycle Control
Presently, a replace lifecycle operation allows a user to substitute one document for another, that is one-to-one. eCTD v4.0 recognizes more flexibility is needed to manage submission content over time. The new standard allows many documents to replace one, or for one document to replace many. This functionality will most likely be used when changing granularity, for example, when you want to replace a legacy study report with it E3 granular parts. Another example is a scenario where you’ve provided too much granularity, such as a drug substance split into several one-paragraph documents that can be consolidated into one.
Metadata plays a more vital role in eCTD v4.0. Keywords are used to group similar information, such as a product, and context of use alludes to the CTD heading, such as 3.3 Literature References.
Another improvement is the ease with which incorrect metadata entries can be corrected. Again, the current version of eCTD is limited; a slight misspelling of a manufacturer, for example, creates separate eCTD sections. If submitted, the errant entry cannot be modified. It must be deleted and added again or you must continue to use the misspelled manufacturer.
eCTD v4.0 includes functionality to correct the display name of a keyword/attribute in a subsequent sequence. For example, changing Ace Manufacturer to read Acme Manufacturer.