Many international regulatory affairs professionals have come to dread the phrase “Module 1 Change” in the past decade. What looks like a simple reshuffling of leaf titles or the addition of a few new submission types grows into a much more complex problem to solve. Those of you in regulatory operations see on thing in large red letters – VALIDATION.
The European Union is taking its turn in 2016. The EU M1 v3.0 final specification was published in October 2015 and is set to take effect July 1, 2016. The specifications become mandatory on October 1, 2016.
As a practical matter, there are a few things you’ll want to discuss within your organization prior to those deadlines if you currently submit to the EU or are planning to in the future. You can also see the progression to eCTD v4.0 taking shape as elements like Submission Unit and Universal Unique Identifier (UUID) appear in the revised specification.
Addition of Submission Types, Regulatory Activities
The first thing your regulatory affairs group will want to account for is the addition of several new submission types and regulatory activities. A number of the EU M1 changes are based on new pharmacovigilance legislation. The policy of publishing clinical data (clinical data for publication), which entered into force on January 2015, and the need to support the application of Certificates of Suitability (CEP) were also contributing factors to the updated specification.
The impact of these changes will be felt as you classify, reference, submit and lifecycle regulatory activities.
Here are a few examples of the Submission types added in the latest EU M1 specification.
Another interesting development you’ll notice when close reading the specification is Europe’s inclusion of the US FDA’s ‘submission unit’ concept. The current attribute of submission type will be used exclusively to describe a regulatory activity. Submission unit type will describe content at a lower level; think of it as a sub-activity of the regulatory activity. Submission unit is designed to provide greater clarity in regard to relationships between sequences. For example, a submission type/regulatory activity of Variation Type IAIN (var-type1ain) would take initial as its submission unit type.
The valid values for a Submission unit type are as follows:
As was mentioned up front, some of the eCTD v4.0 terminology is trickling into the latest EU M1 specification. The EU M1 v3.0 specification describes Submission unit type as a sub-activity, but in eCTD v4.0, Submission Unit is the term for the envelope, meaning that it will contain files that apply to one or more submissions.
Universal Unique Identifier (UUID)
Also mandatory when submitting using the EU M1 v3.0 specification is a Universal Unique Identifier (UUID). The UUID is a 32-digit hexadecimal number that links a sequence to the eCTD application to which it belongs.
In the past, despite the presence of multiple pieces of information to match eCTD application and sequence, such as the procedure number, sequences have been loaded incorrectly by receiving agencies.
European agencies receiving submissions in the new M1 specification will validate for a UUID, however, older sequences and applications will not require retroactive assignment of a UUID.
Unique identifiers such as a UUID are required for many functions in the Regulatory Product Submissions (RPS) standard.
Overall Impact of Global eCTD Changes
You now have a matter of months to prepare for implementation of the new specification. Your regulatory operations group and IT support teams know a software update is on the horizon and should be planning accordingly. eCTD publishing, review and validation software, along with RIMS and product registration solutions will be affected.
Software vendors should, and the emphasis here is on should, be in the process of updating systems to comply in time for the mandate. Cloud-based users will encounter minimal costs.
Costs and effort will be greater for local installations. Plan for a standard validation process and resource impact of a major upgrade.
If I were preparing for multiple changes to global eCTD landscape (FDA M1 update, EU M1 update and adoption in Asia/Africa) as a Global Director of Regulatory Operations, my first directive would be to draft a 5- and 10-year roadmap to support the organization’s eCTD efforts. You will need a clear picture of the impact these initiatives will have on resources and budget.
Software will be in constant flux as each regions redraws its eCTD specifications. One topic I would put on my organization’s agenda, and I’m speaking here to non-adopters, is potentially shifting my eCTD software systems to the CLOUD. Your organization would have an honest accounting of the total cost of ownership for CLOUD versus local installations.