11. eCTD 4.0 and standardized data, with Ben Wimmer

Changes are coming to regulatory submissions publishing and we talk about two of them, eCTD 4.0 and standardized data, with Ben Wimmer.

Episode Transcript

James C Taylor (00:02):
My job at Biologics Consulting other than hosting this podcast
is regulatory submissions publishing wherewe make sure documents being submitted
to the F D A meet their technicalrequirements for receipt and review.
And someone who knows more about thatthan I do is Ben Wimmer, our Director
of Regulatory Operations Publishing andElectronic Submissions, and my boss,
we'll talk to him about it right now.

(00:23):
I'm James C.
Taylor, and this is Insight at Biologics.
Thank you for joining me, Ben,and why don't you tell everybody
a little bit about yourself?

Ben Wimmer (00:42):
Thank you for having me.
So yeah, my name is Ben Wimmer.
I'm the director of regulatoryoperations here at Biologics Consulting.
Hi.
I've been in biologicsfor going on 14 years now.
I've been doing this whole regulatorypublishing thing for about 16 years.
I kind of started out James, as youknow, with you at another place.

James C Taylor (01:06):
True.

Ben Wimmer (01:07):
And eventually moved on to Biologics Consulting., which
obviously was, was a good thing,um, as I've been here so long.
And started Biologics Consulting as apublisher and just kind of learned one
thing after another and eventually wasfortunate enough to be able to, to lead
this group and, and put together a groupof my own here at Biologics Consulting.

(01:31):
You know, we've had a great amount ofgrowth going from two people to 10.

James C Taylor (01:37):
Yes.

Ben Wimmer (01:38):
And so here we are and we're still experiencing this growth
and it's been very organic and.
Just a positive experience all around.

James C Taylor (01:46):
And not to brag on ourselves, but I'm going to, one of the
reasons why our group has experiencedgrowth is the quality of what we do.
And that is due in no smallpart to your leadership.
So now that I've kissed up successfullyto my boss, we'll go ahead and we'll
go ahead and we'll actually talk aboutwhat we're here to talk about, which
is the, uh, environment right now forregulatory submissions and publishing,

(02:11):
especially where eCTD is concerned.
There's a lot of interesting stuffgoing on, and so what are some of
the latest developments in our area?

Ben Wimmer (02:23):
Yeah.
So when people are either in theindustry or, or even out of the
industry, a lot of times will askme, what is regulatory operations?
What is regulatory publishing?
And I always tell 'em it's amix of, it's a mix of regulatory
and information technology.
Because I guess like in a nutshell,what regulatory operations is, is
assembling data, drug data, study data,and assembling it in a way that's easy.

(02:51):
For people at FDA to review and, andbasically just handing it to them in
this nice package with a bow on it,so it's as reviewable as possible.
So basically this technology aspect issomething that's ingrained into our job.
Regulatory submissionshas obviously moved.
You know, it started out with, youknow, printing out, you know, all

(03:12):
this information on paper and puttingbinders together and putting tabs
on the binders so they can, thereviewers at the FDA can find their
way around the information easier.

James C Taylor (03:23):
Right.

Ben Wimmer (03:23):
And then sending a whole boatload of paper to the
FDA's doorstep and letting themlook at this information that way.
So, you know, it's moved on quitea bit, you know, over the years
using this technology aspect.
And that's really always whatthe, the biggest things that are
happening in regulatory publishingthese days are, are always going to

(03:44):
be kind of technologically driven.
And so right now the things that are thehottest topics in the industry in in our
corner of the industry are I would sayeCTD 4.0, which is this next version of
eCTD that is coming up in the next fewyears and is actually available right now.

(04:08):
And the other thing, which is also verytechnology driven is standardized data.
And that's moving a little bitaway from this narrative text--

James C Taylor (04:20):
Right.

Ben Wimmer (04:21):
--that we've been providing to FDA for so long and more into
like a structured data format withmore tabular and data that's simply
structured and easy to navigateand compare and things like that.
But yeah, obviously that narrativeside of publishing is never going to

(04:43):
go away because, but you're alwaysgoing to have to explain your product--

James C Taylor (04:46):
Right.

Ben Wimmer (04:46):
--to a certain degree, explain the data to a certain degree.
But right now, yeah, those two things aredriving the industry more than anything.

James C Taylor (04:53):
And I want to get to actually both of those things.
But one of the other things I want tobring up, because I was given a little
insight on this, no pun intended, inone of my other interviews, is that
the FDA reviewers don't have as muchtime as we might think to get through
a submission, and so that's why it'svery important that what we send to them

(05:19):
is structured in such a way that theycan find what they're looking for and
what they need to review very quickly.
I was talking with one of ourconsultants who prior to joining
us, was an FDA reviewer about theprocess, and I was fascinated by how
little time they seemed to get versushow long a time I thought they got.

Ben Wimmer (05:42):
Mm-hmm.

James C Taylor (05:44):
So...

Ben Wimmer (05:46):
Absolutely.
And if you look at things like we'veseen in recent years, like, you
know, the Covid 19 pandemic and drugsgetting emergency use authorization,
then you see they get even lesstime than they normally would have.

James C Taylor (06:01):
Exactly.
When you're, you know, in hurryup mode trying to save the world.
Yeah.
You don't have time to haveto hunt and peck for things.
Now first, because sometimes I knowpeople get lost with alphabet soup.
We've said eCTD several times.
That is the electronic common technicaldocument, and it's a format that's
been agreed upon by regulatory agenciesaround the world on how to structure

(06:27):
a submission to a regulatory agency.
So that's what that means.
And we're just going to sayeCTD from this point forward.
There've been numberof iterations of that.
And the newest comingonline right now is 4.0.
Correct?

Ben Wimmer (06:41):
Yep.
4.0 is the newest iteration.
You know, the goal of eCTD is alwaysto make things more universal across
the multiple regulatory agencies.
And so eCTD started as somethingthat was, you know, at least most
of the eCTD package was going tobe universal across, you know, you

(07:01):
could submit a product to an agencyin one region like the United States.
And an agency in a far away region like,you know, Japan or Australia, and, and
still have the same basic structure witha little bit of tweaks here and there
for what that local agency likes torequire for their specific requirements.

(07:22):
And so eCTD 4.0 is kind of taking thata step further and shooting for this
universal approach, which is, again,it's always been the goal, but they're
taking that a little bit further,you know, in a few different ways.
Not just across different agencies,but also across, you know, things like
different product types, especially tothe FDA, meaning that eCTD 4.0 is going

(07:49):
to support not only drugs, but also thingslike, you know, medical devices, tobacco
products, cosmetics, things like that.
So that's something that's alwaysin the mind of the people that
write this stuff and promote, youknow, these new iterations of eCTD.
That whole universal approachis heavily in the background.

James C Taylor (08:09):
Now, right now, 4.0 is not mandatory, but it is available.
How would you advise a client to proceedwith preparing their submissions, both
current and going into the future?
For instance, is there an optionto convert an existing application

(08:35):
to 4.0 or do they have to startin 4.0 from the beginning?

Ben Wimmer (08:39):
So yeah, they would have to start in 4.0 from the beginning.
Because it's in its infancy.
The 4.0 is currently, currentlyoptional and will be mandatory
in about five years, so 2028.
But to answer your question, I wouldadvise sponsors with original applications

(08:59):
to go ahead and get on 4.0 as soonas possible and be one of the first
passengers on the train, so to speak.
To get to that destination a little bitsooner is going to save you some trouble.
In the long run, it's going to saveyou a lot of trouble, especially if
we're talking about waiting untilit is mandatory and you have to
scramble and put resources togetherto meet the mandate and potentially

(09:22):
experience delays and things like that.
But personally, I'm always in favorof getting on these requirements
as early as possible as soonas FDA starts to accept them.

James C Taylor (09:34):
You know, I've done a few of these shows now, and that seems
to be a common theme with all of our,all of our guests, that it is always more
advisable to get in on these areas early.
Now, if someone is unsure of how toset things up, Even though we tend

(09:59):
to be in our position, one of thevery last things that happens, we
can help them at the very beginning.
Correct?

Ben Wimmer (10:07):
Correct.
Yes.
I mean, I would just recommend, youknow, checking with your regulatory
publisher and first of all, seeif they offer it at this point.
It's not going to be a thingthat every publisher offers, so
make sure they can handle it.
You know, most eCTD software systemshave now been updated and converted to be
able to handle 4.0, but not all of them.

(10:28):
So you just want to make sure you'redealing with a group that's able to
support it, that has a tool that's ableto support it and talk to 'em about it and
and to see if they can support it or not.
And as you know, it's something we've beenimplementing here at Biologics Consulting.
You know, we've been working behindthe scenes and testing out 4.0 and
putting together Alpha test submissions.

(10:50):
So we can support this need, andit's something that we're able to
do, and we're fortunate enough tohave one of those products that's
able to handle it this early on.

James C Taylor (10:59):
Right.
And that's a key thing.
You do need to check with your publisherto see whether or not their present
system can even run a test on it,because as you said, not everybody can.
Now, one of the things thatwe want to talk about as well

(11:21):
was the standardized data.
Can you just give a broadexplanation as to what that is?

Ben Wimmer (11:32):
Yeah, so in terms of publishing standardized data, we
internally and publishers refer to 'emas datasets, but it's, it's basically
just files of data that's standardizedand tabular formats and formats that
are easy to compare on FDA side.

(11:53):
So it's easy to compare data fromall kinds of different angles.
You know, typical, you seedifferent file types put together
for standardized data, the mostcommon would be XML or dot XPT, SAS.
Those are all file typesthat are common that kind of
encompass the standardized data.

(12:16):
So essentially what it means in terms ofFDA reviewers reviewing the data is it's
a step away from PDF based technology tostep away from narrative based technology.
It's in a step towards a more scientificformulamatic approach, and that's

(12:39):
kind of what it is in a nutshell,
but from our perspective--

James C Taylor (12:43):
Now you go-- I'm sorry.
Go ahead.

Ben Wimmer (12:44):
Oh, sorry.
I was just going to say, from ourperspective right now, we only
see non-clinical and clinicaldata available in this format.
But in the future, there's a highlikelihood that we're also going to see
CMC data provided in the same format.
Because again, it's all about FDAexpediting the review times, and from

(13:10):
their perspective, it's a lot easierto run these data sets through the
programs that view and assess them,and it's easier for them to compare and
contrast the data using that method thanit is to flip back and forth between
tables and PDFs or paragraphs and PDFsbecause they have actual numbers at

(13:31):
their fingertips, and it's becomingvery, very popular on the FDA side.

James C Taylor (13:38):
Now, some people in our industry are a little wiggly about this
because one of our skillsets is verymuch based off of the generation and
manipulation of PDF documents and whatI think they're not taking into account,

(13:59):
and one of the things I believe we hereat Biologics are very well positioned
for, is that this is still going torequire a lot of knowledge of formatics.
It's just that instead of manipulatingpages of PDFs, we're going to need
to make sure that all of the datathat is required is available and

(14:23):
it is in the correct data type.
And so we will be able to help youeven if you move to this direction
because we understand this sortof XML based structure, correct?

Ben Wimmer (14:43):
Correct.
Yeah, absolutely.
It's something we've been dealingwith for, for quite a few years now.
You know, FDA's had a sendrequirement in place for, I
don't know, 5, 6, 7 years now.
And SEND is the standardexchange of nonclinical data.
So that's basically FDA's requirementthat, you know, certain types of

(15:05):
nonclinical studies are required toinclude this standardized data in addition
to the good old fashioned study reports.
You know, you mentioned that makesgetting away from the PDF based kind
of background makes some people in theindustry a little squeamish because
they've been doing that for so long.

(15:26):
But as you mentioned, you'rekind of doing the same thing.
You're taking the data, you're assemblingit, and a format specified by the
agency and providing it to the agencyexactly how they want to see it, which
is, you know, what we were doing withPDFs before, we're just doing it in
a different format that's, you know,easier for them to access and review.

(15:48):
We're just doing different things.
We're, we're able to take that dataand place it in, in the eCTD structure
exactly like FDA wants to do it and theway they want it is they're more and more
requirements to how they want it done.
So I feel like people that are alittle worried about moving on from
the PDF based process don't haveto worry so much because you know,

(16:13):
there's still going to be work thathas to be done by the publishing teams.
They still have to put this data together,format it, and lay it out exactly like
FDA wants to see it in the right placesunder studies and, and things like that.
And so that part's not going to go away.
And the PDF side of thingisn't going to go away.

(16:33):
That's, you know, like wetalked about eCTD 4.0 earlier.
They've been working on that for along time and they retained module two.
I can't really think of any way you canget away from a narrative based approach
with module two because module two isessentially summarizing your CMC, your

(16:54):
nonclinical, and your clinical data.
And I think e- even though earlier I said,you know, we're likely going to see more
of this database approach to module three.

James C Taylor (17:03):
Mm-hmm.

Ben Wimmer (17:04):
I think you're still going to see for a long time, this PDF narrative
based approach, and, and even after theystart making requirements for a more
standardized data, I think you'll stillsee the narrative based text to go along
with it, kind of like we see in modulefour with those nonclinical sections.

James C Taylor (17:22):
All right, so if anyone has any questions on 4.0 and
readiness, they should feel free tocontact you and check it out, correct?

Ben Wimmer (17:35):
Absolutely.
Feel free to contact me if you have anupcoming application and you're thinking
about getting ahead of the game and beingable to provide your IND, your BLA, NDA,
drug master file, anything to the FDA inthis format, and you just want to be ahead
of the game a little bit and want to giveFDA a chance to ex- expedite your review.

(18:03):
Feel free to reach out to me or, orany members of, of our team here,
and we would be glad to take thatproject on and help you with it.

James C Taylor (18:09):
Indeed.
And if you'd like to contact Benor me or anybody else here at
Biologics Consulting, just email usat [e-mail].
That's Insight at BiologicsConsulting, all one word, dot com.
Thank you Ben for joining us today.
Also, we'd love it if you, ourlistener, would like, subscribe,

(18:32):
rate, and review our show.
The executive producer of Insightat Biologics is Kris Kraihanzel.
This episode was producedand edited by James C.
Taylor.
Technical supervisor is Jeff Wease.
The Insight at Biologicstheme is by Tom Rory Parsons.
I am James C.
Taylor.
Thank you for joining us and pleasecome back for more Insight at Biologics.