Canada, eCTD, eCTD 4, EMA, FDA, Health Canada

eCTD 4: Everybody in the pool! But no running!

This year’s Regulatory Information, Submissions, and Document Management forum presented by the DIA took place February 4-7 in Bethesda Maryland. I saw a lot of old colleagues from my employers over the decades, now dispersed throughout the industry, and heard a lot about where Regulatory Information Management is heading.

For me, the most fascinating part of this conference each year is the presentations from the agencies: what’s been happening lately, and what can we expect for the future. Both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) report that the electronic Common Technical Document (eCTD) is pretty much universal, there are only a few stragglers out there.

— but there shouldn’t be any submissions that aren’t in eCTD format for the US and Europe. As of the first of this 2018, eCTD is mandatory for most European submissions, and as of May 5 of this year (less than three months away at the time of this writing), eCTD will be mandatory for US Investigational New Drug and Master File submissions, making it universal except for things such as institutional INDs. If you will be struggling to get to compliance with this requirement, please let us know: ARIM can be made available in the cloudquickly, and our ARCS team is available to process submissions on your behalf.

And that brings us to eCTD version 4. For a project which was approved as an ANSI standard three years ago, and has been worked on for over 10, it’s been a long, slow implementation. I was pleased to see that the US, Europe, Japan and Canada all committed to implementing eCTD 4.

The US FDA has unfortunately let their schedule slip – last year, FDA projected that their pilot would begin in the second half of 2018. Now it appears that the second half of 2019 is the likely start for the pilot. Mark Gray of FDA said that we are “still a couple years away until we open the doors.” The good news, though, is that they are emphasizing their long-term dedication, and that future changes to of the eCTD will only take place on eCTD version 4.

Health Canada’s presentation by Vikesh Srivastava was a little more optimistic: they should be issuing draft guidance during the first quarter of 2018, for a pilot in 2019 and acceptance in 2020. This stands a chance of beating FDA or Europe to acceptance of eCTD 4.

Mikel Hedemand of the Danish Medicines Agency also talked about their plans, which aims for optional use in 2020 if they have the internal tools ready. It’s likely that their initial implementation may not include two-way communications, since for Europe it’s really 33-way communications which makes things much more complicated. I spoke with one of the European regulators after the session (I don’t think it was Mikel, but I’m bad with names), and he said that the issues I’d previously identified are being worked on, but they haven’t published anything yet. There is a concern that to identify the reference member state in the eCTD 4 backbone might require a change to the Regulated Product Submissions (RPS) standard that eCTD 4 is built on. That would be unfortunate: I’m hoping that they can find a workaround, or leave it out of the backbone entirely, as it’s also in the electronic application form.

Harv Martens, who has worked closely with Japan’s JPMA and the International Council for Harmonisation , also said that 2020 is the target for pilot use with acceptance and mandatory use in subsequent years. Japan may also adopt the more flexible lifecycle approach used by other regions, meaning that it would not be a new application to do what is a supplement in the US or a variation in Europe.

I’m still very optimistic about eCTD 4: Not only will it allow more flexible document lifecycle, and correction of errors in metadata that currently linger for years, it should lower costs as the general RPS framework is adopted by other regulated industries such as medical devices, veterinary drugs, food additives, etc. Please contact ACUTA to learn more about how our ARIM software will incorporate this new standard.

eCTD 4 reference information:

EMA eCTD 4 Page

ICH eCTD 4 Page

FDA eCTD 4 Page

HL7 RPS Standard Page

Photo Credit Adam Russell

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.

3 Comments on “eCTD 4: Everybody in the pool! But no running!

  1. Hi Joel,
    Yes, it was actually me you talked to briefly during the RSIDM 🙂 Our major concern is not so much how to identify the reference member state, but rather how to define for which countries a section is relevant. If a product has forms/strengths 001-004, and 001-003 is approved in countries A, B and C, and 004 is approved in countries A, D and E, then we may have submissions/sequences/documents that are relevant for just form/strength 004 and for this reason only relevant for countries A, D and E. There should be a structured way of informing countries B and C that these sequences and documents are not relevant for them — meaning it does not have to be registered at these countries, the assessors do not have to look at these documents, and it is not a mistake that the documents/sequences are not present.
    The information needs to be n:n, and it must be aditable during the lifecycle since forms/strengths may get approved in ot withdrawn from countries thus changing for which countries a section/document is relevant.

    1. Mickel, That’s an interesting problem, and not one that has been designed into RPS. We can identify one particular recipient for each TOC item, we can exclude an item from a regulatory activity in a bundled/grouped/workshare submission. A tweak to the primaryInformationRecipient to allow multiple, and perhaps an attribute indicating its usage, would probably give you the functionality you need, but that means a revised standard.

  2. … and I forgot to emphasise:
    This challenge is no different in our current eCTD 3.2.2. So eCTD 4.0 does not introduce a noew problem in this area, and it will not be a stop us from moving forward with eCTD 4.0. It just does not fix a current problem.

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