ACUTA, ARIM, ARIM Publisher, eCTD, EMA, FDA

Lots of Regulatory Activity Going On

Welcome to another episode of Fun With RIM (kidding, this is the first one). Today’s topic: Just what is a Regulatory Activity? You’ll say to yourself, “I’m in Regulatory, and I do things, so those must be Regulatory Activities.” Not counting that 15 minutes to two hours that half the workforce spends every day on social media, ok, maybe.

What’s really meant by a Regulatory Activity is a group of communications (such as submissions) to accomplish something. Often that “something” is a set of submissions to a regulatory agency, but it could also involve working with a manufacturer on their compliance, with a partner on a marketing contract, or a potential acquisition. On the submission side, it could be an original application to one agency, it could be the need to update the name of a supplier for ten products for thirty agencies. Other activities would include registration of a clinical trial, annual reports, or just a response to questions.

The idea has been around for a while in electronic submissions. The European Medicines Agency (EMA) defines it in their Module 1 specifications for the electronic Common Technical Document (eCTD):

A single sequence or a collection of sequences covering the start to the end of a specific business process, e.g. an MA [Market Authorization] application or Type II variation.

In the submissions themselves, though, there is no “Regulatory Activity” as a thing, it’s merely the sequences connected by a Related Sequence number– using the first submission that was sent for that business process to tie the collection together.

The US Food and Drug Administration (FDA) Module 1 specifications also has had the concept of a “Related Submission” – the sequence number in a particular application that started the regulatory activity. FDA uses, but never actually defines Regulatory Activity in their documentation, though: it’s stored in a concept titled “Submission” – which is quite confusing since a single submission sequence is usually just called a submission. Note that eCTD 4 won’t really fix this either; it talks about a Regulatory Activity, but deep inside the XML, it’s still labeled a submission.

The good news is that with the concepts of bundled submissions (FDA), and grouping and worksharing (EMA), submissions across multiple applications – even multiple products – can be associated into a single regulatory activity. It’s still a little funky to look at in the current eCTD submission, but at least that’s one place where eCTD version 4 will really make things clearer.  I’ll cover this in depth in a future post.

The idea of the “related submission” has led to a lot of errors at the agencies, where responses to questions about an amendment gets ‘related’ to the amendment, instead of the original submission, or multiple sequences are listed. The agencies have, for the most part, been pretty lenient about these errors, although it frequently comes up as one of the top ten problems in FDA’s presentations at DIA meetings. It makes a mess out of importing submissions into publishing systems, too.

By calling something a Regulatory Activity, it helps organize your thoughts around all of the activities that pertain to that business process (partner communications, initial approval, supplement/variation, annual report, etc.).  Understanding it as a regulatory business process, should clear up how to use it properly. This regulatory process need not be limited to submissions and applications, as in previous versions – and in competitor products, where you might be limited to thinking in terms of application-defined events and may have had to create a fake application in order to group things together. The ARIM Regulatory Activity makes this all easier by giving them a connecting thread.

ACUTA’s ARIM has been enhanced to support this concept, starting with version 3.1. The Regulatory Activity lets you group sequences and correspondence, enter the information about the group just once, and keep track of the status for that process. The Regulatory Activity is created or linked to when you create a sequence or correspondence, and in Viewer, you can limit the view to just the sequences associated with that activity: all the metadata for that activity is in one place, simplifying the process.

ARIM Regulatory Activity

This also makes it simple to see the documents associated with a Regulatory Activity in the ARIM Viewer. In addition to viewing a single submission sequence or the overall cumulative view, a cumulative view of a Regulatory Activity may also be selected.

Regulatory Activity view in ARIM Viewer

When working with submission sequences in a Regulatory Activity, they will all be associated with the same application type and submission type.

Submission Type  Sub Type
Original Application Presubmission, Application, Amendment, Resubmission    
Efficacy Supplement Presubmission, Application, Amendment, Resubmission    
CMC Supplement Presubmission, Application, Amendment, Resubmission 
Labeling Supplement Presubmission, Application, Amendment, Resubmission 
Annual Report Report, Amendment
Product Correspondence Correspondence, Amendment
Postmarketing Requirements or Postmarketing Commitments Original, Amendment
Promotional Labeling Advertising Original, Resubmission, Amendment
PADER/PSUR Report, Amendment

Application and Submission Types for US NDA/BLA

Future versions of ACUTA plan to extend the concept of the Regulatory Activity beyond applications (eg. a facility inspection) and add a “Master Regulatory Activity” to include multiple products, or multiple agencies. This would permit organizing submissions and commitments related to a manufacturing change that affects multiple products, filed with multiple countries.

In the meantime, the ARIM Regulatory Activity simplifies the organization, creation, and viewing of related communications and submission sequences, and prepares you for the future of eCTD version 4.

Contact ACUTA for more information about ARIM, and how its cloud-based publishing and submission management tools can streamline your company’s regulatory activities. (And come back for the next episode of Fun with RIM!)

Author: Joel Finkle

Joel became embroiled in electronic submissions when regulatory came downstairs and asked "Can we convert all our clinical study reports to WordPerfect format for the FDA reviewer?" and he didn't say, "No." Since then, he's been involved with custom CANDAs, PDF publishing, eCTD, document template automation, Regulatory Information Management, HL7's RPS, and the ISO IDMP standard. He joined ACUTA in April of 2017. He'd share some of his famous tomatillo salsa with you, but he can't carry it on airplanes.

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