March 19, 2024 • 22 mins
In this episode of Conversations in Drug Development, host Dr Harriet Edwards is joined by Katy Rudnick and Dr Julie Warner from Boyds to discuss US regulatory trends and initiatives at the FDA. This episode explores the FDA's recent organizational changes, pilot programs, and focus on innovative clinical trials, including the use of AI in drug discovery. Join us for another Conversation in Drug Development, exploring the dynamic landscape of regulatory trends expected in 2024 and beyond, with a key emphasis on the US scope.
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Episode Transcript
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(00:00):
Music.
(00:05):
Hello, and a warm welcome to the latest edition of Conversations in Drug Development,
brought to you by the team at Boyd's.
This podcast is for our fellow community of scientists and clinicians working
in the wonderful world of cell and gene therapy and drug development.
Thank you for tuning in, and we hope you enjoy the conversation.
Music.
(00:31):
Hello, and welcome back to another installment of Conversations in Drug Development,
My name's Harriet Edwards and I'm your podcast host for today's episode.
Today's episode is building on the theme of our first 2024 episode,
where we discussed hot topics and trends to look out for in 2024.
This time, we'll be taking a deeper dive into regulatory topics,
specifically in the US, to decide what trends to be on the lookout for.
(00:55):
I'm pleased to say that today I'm joined by not one, but two of our senior regulatory
team here at Boyd's for today's discussion. discussion.
Katy Rudnick, our Head of US and Dr.
Julie Warner, our VP of Regulatory Affairs.
Katy and Julie, welcome to the podcast. Thanks for being here today.
Hi, Harriet. Thank you. Hi, Harriet. So I guess we've kind of built this podcast
(01:15):
episode as trends and things to look out for in 2024 with a specific focus at
the FDA because there's loads of interesting developments and lots going on.
So I guess that's a good place to start.
So Katie, after the ups and downs of last year, what's going on at the FDA?
Sure. Right to kick off the year, there are a few major changes.
Firstly, Janet Woodcock will be departing at the end of the month.
(01:36):
In her stead will be Nemanja Bumpus, who has been chief scientist since June of 2023.
Some of her main focuses will be on foods. And in her history,
she's done a lot to expand the cosmetic regulations.
So we'll have to see how this plays out for drugs. Another big change is that
FDA will be going through yet another reorganization. the Office of Regulatory
(01:58):
Affairs will be transformed into a new Office of Inspections and Investigations.
So many of the current offices will be impacted. However, the changes are meant
mainly to be focused on inspections, investigations, and import operations.
So the change is meant to help ship these compliance-related functions under
a better structure and chain of command for those activities.
(02:19):
So another objective of the RE-ORG
is to stand up a brand new Office of Regulatory and Emerging Science.
This does seem to be duplicative to the existing Office of Regulatory Science
and Innovation. So time will tell what functions overlap there.
Okay, so definitely something to watch out for, particularly if people are planning
interactions with the FDA, they may be going to a new office for those.
(02:41):
Yes, we'll have to see how that plays out. There is a nice structuring on the
FDA website, if anybody would like to check that out, that shows which offices are impacted.
Great. And then other developments, I know there's quite a lot of initiatives
that we'll touch on today as well.
Yeah, a few of those I can discuss in a little bit more detail.
So last year, We saw the introduction of several measures and schemes all across
(03:03):
the board with the CMC development and readiness pilot.
Also, the START trials initiative, which we'll speak to in a little bit.
We've also seen FDA's first thought paper on the use of AI in drug discovery.
And additionally, CDER initiative on innovative clinical trial approaches.
Interesting, both of these latest two items reflected on instances where the
(03:26):
FDA has said, please come talk to us.
We're looking for your feedback and your comments and input on what's important
as experts and drug developers. And then there's Operation Warp Speed as well, right?
Yes. So Operation Warp Speed was pretty successful during COVID-19 pandemic response.
And so the agency really intends to continue to utilize this moving forward.
(03:47):
It's a partnership between the HHS, CDC, FDA, NIH, and several other government agencies.
And it basically lit a fire under some of the programs to give enhanced government support. support.
So with FDA's focus on rare diseases, it's thought that this will be an area
of concentrated development and to move those programs speedily through the process as well. Right.
(04:10):
And there's actually a lot to unpick there. You've just mentioned,
just rolled off the top of your tongue, lots of initiatives.
And I'm sure we're going to unpack those throughout the course of the podcast
in a little bit more detail. But before we do, all of them sound very promising.
So I'm looking forward to hearing a little bit more information about them
but I know I have to say a nod to one
of the most exciting things that happened for me personally as
(04:32):
somebody that's keenly interested in genome editing was obviously
the FDA's approval at the back end of last year of
the first CRISPR-based medicine so that was
of course hot off the heels of the MHRA here in
the UK who were of course the first people to approve the first ever CRISPR-based
medicines are very exciting and I guess that brings us nicely on to thinking
about different territories and duly specifically the the EU it's been clearly
(04:57):
very innovative 12 months for the FDA as Katie's just mentioned it's the same
thing happening over in Europe?
Well, Harriet, I really have to take my regulatory hat off to FDA.
They've really pulled a series of initiatives out of the bag that will help
developers have an expedited dialogue with the agency when it's warranted,
when it's truly warranted.
So we have had some measures introduced in Europe. So we have the MHRA's Innovative
(05:20):
Licensing and Access Pathway and IDAP, the equivalent for devices.
But we truly haven't seen anything along the lines of what FDA is doing at scale in Europe.
And let's not forget, it's only this year that we've seen EMA
join Project Orbis which has been running since 2019 as
an observer and not actually even as a participant and this is maybe because
(05:41):
anything at the centralised European level just is so much more difficult to
coordinate with 27 member states being involved and all of the political and
legal backdrop that you know is behind that so I think it will just be interesting
to see how this plays out over time.
Yeah absolutely and I think maybe that's a topic of Another podcast is talking
about how the EU come together with 27 different opinions to form a centralised
(06:06):
sort of harmonised approach to things.
So watch this space for a different podcast on a different day.
But let's go back into the FDA initiatives, Katie, because we've mentioned quite a few of them.
And I think lots of interesting developments to talk about.
But maybe we should begin in the clinical trials arena at the start of drug development.
And maybe that That is a good place to start the START initiative. Exactly.
(06:30):
START is an acronym for Support for Clinical Trials Advancing Rare Disease Therapeutics.
This was initiated in the last half of 2023 as a pilot program.
So this engages more frequent FDA communication in hopes of resolving clinical development issues.
And Dr. Marks, the director of CBER, has seemed to really champion rare disease
(06:51):
treatments. and we continue to hear promise of more FDA efforts to assist sponsors in this area.
But START also crosses over into CDER as well with a slightly different qualifying
requirement set, but applicants can go ahead and sign up until March.
However, this is a very small pilot with only three INDs to be accepted under each center.
Oh, wow. So if you do get involved, then you're very lucky if you're successful in this application.
(07:16):
There are some other efforts though. Continuing on is the ARC program for or
accelerating rare disease cures.
And this does have a brand new offshoot called Leader3D. It's currently soliciting
rare disease drug program development information to fill knowledge gaps in
development regulation.
And the docket for this is open through the end of April. It's open to industry,
(07:37):
but also patient groups, academia, basically anyone who would like to submit to the public docket.
And FDA's wish for this is to create a publicly available resource on submitted topics.
It's a bit unclear what direct benefits are to be had by the stakeholders.
Other than just some general information on stumbling blocks or,
you know, areas of interest. So we're yet to see what comes from that.
(08:00):
And a different kind of initiative. I mean, the START program,
the pilot that you mentioned, there are obviously clear benefits for successful applicants there.
But it will be interesting to see how well received the ARC program is,
particularly with regards to whether or not industry want to share their development
programs and divulge maybe confidential information. So, yeah,
(08:21):
definitely one to watch to see how successful that is.
Yeah. And I'm really excited to see how the start pilot pans out as well,
in particular, whether it will have a broader scope than perhaps just clinical
items and whether it will help to take some non-clinical and CMC issues off
the table or whether you would still have to pursue those via other means such as CDRP.
But I guess, yeah, again, early days, we'll just have to see how that pans out.
(08:44):
It's really good that you've mentioned CDRP there, Julie, and I think maybe
we can come on to that in a moment. But just to continue the theme on clinical
trials, there is also an initiative by CEDA around innovative clinical trial approaches.
So, Katie, can you tell us a little bit more about what that actually means?
Absolutely. So FDA is currently in a data gathering period.
(09:05):
Basically, they're looking for general pros and cons to collect these of different
feedback bits to understand the pain points.
Is there are some innovative trial designs with newer elements,
new technologies, and these types of things also include real-world data,
which we've experienced for a while now, but AI.
And, of course, that comes in many different formats. So right now they have
(09:26):
workshops and listening sessions that are currently underway.
Comments to the docket close in spring, in April.
So FDA has acknowledged many times that they're always in a game of catch-up
with emerging tools and technologies.
And so they're cognizant that this information gathering step is the first step of the puzzle.
And following on with feedback sessions is their typical way to kind of stew over things.
(09:50):
And eventually they'll reach into a guidance writing period.
They have been extremely vocal about AI and just acknowledging that if you aren't
investigating it and putting efforts into incorporating it into your programs,
you're a little bit behind the curve already.
Yeah, and that's really interesting. I don't think that's specific to FDA actually
commenting that they're a little bit behind the curve in terms of development
(10:12):
of AI and developing regulation and guidance to support.
I think that's across the board and regular listeners to the podcast will remember
that we actually recorded an episode specifically on AI last year.
And actually half of the information or maybe even more is probably outdated
already because there have been so many developments in this area.
So Julie, you were on that podcast with me as well.
(10:35):
Any updates to how the EU regulators are looking at AI since we last talked about it?
Yes, a couple of big developments in December, Harriet, and is it really six
months? It feels like five minutes. I know.
We had a provisional agreement between the European Parliament and the Council
on the AI Act, which is the first EU-wide regulation on AI.
(10:56):
And secondly, the EMA's Management Board agreed to a work plan to 2028 covering
several really important elements on on the use of AI in drug development.
And that work plan recognises the incredibly fast-paced nature of the field
and that we need to consider significant elements such as data protection and
ethics and the need for consultation.
(11:17):
So we have had some movement and it's been really great, but I totally agree
with Katie. It just always feels like we're behind the curve on this.
Yeah, it's nice to know that Europe are not necessarily falling behind the US
on this one. It's just generally everybody's falling behind the speed of development of these technologies.
So lots going on in that space and lots to look out for in terms of how the
(11:39):
use of AI and other emerging technologies can actually accelerate clinical trials.
But of course, all of these things are only good if everything else that supports
the use and the initiation of clinical trials can also keep pace.
So just thinking out loud, really, about manufacturing, that has to keep up
with all of the other innovative things that we're doing around clinical trials,
(12:00):
study design and things like that.
So going back to what you mentioned around the CDRP pilot at the FDA,
that's specifically focused around CMC and manufacturing.
Katie, can you give us a little bit more information about that and maybe any
experience that we've had with this pilot so far?
Sure. Just to touch further into that. We're into the second year for the CMC
(12:22):
Readiness and Development pilot.
This is really nice because it does offer two specific CMC Type B meetings,
inclusive of follow-ups and different communications.
So the sponsor does have a direct benefit immediately.
The goal is a quicker CMC agreement for programs and accelerated clinical development
or an overall quicker product approval.
(12:42):
And everybody wants that, of course. We know of two companies to date,
both Bicycle Therapeutics and Raise Bio, have been public about their involvement in the pilot.
So we know that it's going on and there are some activities in this space.
So we just kind of have to wait a little while and see how that goes and what
else they're able to publicly share.
I have to say, Katie, I think this feels like 1-0 to FDA again.
(13:03):
Again, as previously mentioned, it may well just be down to the fact that,
you know, we have 27 member states to accommodate in Europe,
but also we have a slightly different regulatory approach in that we don't have
the cradle to grave system, you know, that there is in FDA with an IND.
So everything's a bit more disjointed from a European perspective.
So I think one area that it would be good to see this impacting on is the potential
(13:24):
for more global harmonization, which feels like it's coming,
but it's just going to take some time to come in. and we just don't know to
what degree it will, but it's a really exciting space to watch.
Definitely something to watch. And as you said, Julie, I think it's something
that will become more and more prevalent over 2024.
We have to make sure that particularly CMC development can keep pace with all
(13:45):
of these other innovative initiatives that are ongoing. So definitely one to watch out for.
Another pilot that FDA, just flipping back to FDA with all of their many pilots,
another pilot that had been recently announced, Katie, was the first iStand.
Pilot program for AI-based and digital health technology for neuroscience,
(14:05):
which is quite exciting as well.
Yeah, the agency has a few different drug development tool qualification programs.
These help developers with measures that aid in drug development and regulatory review.
We're talking about biomarkers, novel clinical outcome assessments,
and other different tools and technologies.
However, these programs are often specific, and so the I-STAND,
(14:28):
so the The Innovative Science and Technology Approaches for New Drugs,
to spit that all out, pilot program, is designed for those who don't fit the current programs,
but which still have great value.
So the AI-based entry into iStand is really exciting, as it is one true tangible
example of how rapidly AI is moving into the drug development space.
(14:49):
Different project using machine learning models to derive the clinician-reported
outcomes for, say, depression and anxiety. And it encompasses two key technologies
at the cutting edge of medicine, giving FDA the opportunity to really drive
regulation in the field.
I think this one particularly is very exciting because it builds further on
(15:10):
the docket and the innovative trial approaches that we were mentioning earlier
in the podcast to actually give something tangible and supportive to AI developers.
So I think personally, that's a really encouraging sign and something building
further on just guidance.
But that's quite unique, I think. Julie, is there anything similar in terms
of offerings from the EU? you?
(15:30):
Well, we have longstanding programs to help with qualification of novel methodologies
in their use in clinical trials.
And obviously, we have the routine scientific advice procedures.
But again, nothing specific along these lines that FDA has introduced.
But that leads me to conclude that this is really another goal in the net for FDA.
So I think it's clear to say that FDA are leading at the moment in initiatives, which is great.
(15:56):
And And I guess we've mentioned so many already.
If there can be anything else, what else is there? And actually,
there is something else to mention.
FDA have just announced a quality management maturity program,
and that's to incentivize drug manufacturers to go even beyond GMP,
so good manufacturing practice.
Presumably, Katie, that's in an effort to help address future drug shortages,
(16:20):
for instance, or something else. Can you give us any more insight onto that?
Yeah. Yeah, FDA's focus here is really on encouraging manufacturers to take
a more holistic and ingrained approach to their quality management.
It's early days here. This was only announced at the end of January,
and very few sponsors will end up being selected to participate.
But interestingly, the FDA has stated they plan to acknowledge these establishments
(16:42):
and kind of call out the successes.
So I'm not sure how this will be done, whether it's on a private or public scale.
But in the end, participants will have the opportunity to see how they measure
up against the other pilot companies in an anonymized manner.
However, they will get to see the outcomes.
And it's just a very interesting and different perspective.
Yeah, absolutely. And not something we typically see. So as you said,
(17:04):
very interesting perspective.
I think it's looking like it's going to be a very busy year over at the FDA
and perhaps even at the EU if they maybe want to keep pace.
Certainly as busy as it was in 2023.
I don't know whether, Katie and Julie, if there's anything else,
I know we've mentioned a lot today, but is there there anything else that we
maybe should be keeping an eye out for in 2024 any other activities,
(17:28):
Well, of course, these pilot programs exist and are in place,
which is great, but it will take a while for those to roll into regulation.
There are some apparent FDA kind of hot topics that they're pushing,
and those are rare drugs and further collaboration.
So we can look forward to different advances in those areas.
And a review of the 2024 legislative goals shows a focus on foods, animal products,
(17:51):
a general tightening up of regulations already in place, and of course,
considerations for future pandemic scenarios.
But knock on wood, I really don't see anything I would consider to be disruptive
to our current processes for the remainder of the year.
FDA's voice lately has basically been a positive influence to quicker patient
access and more frequent communications, advanced knowledge sharing up above
(18:16):
and beyond anything we've seen thus far.
And I think we'll see the typical drag times for getting these guidances caught
up to all the pilots and the different initiatives that are in place.
Yeah, and I think from the European perspective, we obviously know that the
revisions to the pharmaceutical legislation will be coming.
Yeah we don't know what and we don't know when because i
think the original proposals were quite far reaching and
(18:37):
quite a lot of consultation on those and there will be some changes
coming i'm sure but we just don't know when yeah topic for
another podcast i was just going to say the exact same thing
i definitely don't think we could cover that in sufficient time today but certainly
something to watch and yeah do watch this space we will cover that in a future
podcast sure and harriet there's one other topic here too there's potential
(18:58):
for ramifications of moving through
through these clinical development programs at an accelerated rate.
Of course, we want to give those our best efforts, but we also have to remember
we're working with a limited data set at this point.
So we shouldn't forget that FDA is vigilant, clear through the development program
and beyond into the approvals phase.
So we've seen a few changes here in that there is a recent black box requirement
(19:21):
for CAR-T products. Yes. And-
This is where they've requested very specific labeling requirements and additional
lifetime patient monitoring to patients in the immunotherapy trials.
So it just shows that there is active monitoring of all these things.
And although we're trying our very best to get these developments processed
(19:42):
through and get the science, you know, on top of things, we do need to be vigilant
and continue to monitor.
I can happily report this is one area where Europe is keeping up,
importantly. Certainly.
So we know that the EMA's Pharmacovigilance Risk Assessment Committee started
looking at the safety of CAR T products as well in January.
And obviously we are now around February time.
(20:02):
That review is still ongoing and should be concluded soon.
We don't know whether the UK MHRA is also looking at this.
They haven't published anything in the public domain right now,
but it wouldn't surprise me if they are looking at it too.
So I think it will be interesting to see how those reviews line up with the
FDA's position and how these products will further align as time goes goes on. Yeah, definitely.
Yeah. One thing to note here too, is that although the FDA has a virtual airport
(20:28):
full of pilot programs, it's not always going to be the best fit for all development programs.
So sponsors really need to take a look at their program timelines,
budgets, and different things, because with advanced communication.
There also becomes more busy work to do and it doesn't always fit the scenario perfectly. So,
(20:48):
take a close consideration, see what programs exist and see if you can leverage
those to benefit your timelines.
That's really good advice. And I was just going to say, actually,
I can't believe we've whizzed through so many different initiatives,
so many different things to look out for.
I honestly think, as I said earlier, 2024 is going to be a very busy year for
(21:09):
anybody that's going to be working in the US space, whether it be early clinical
development or whether it be later into licensure. There's lots to look out for.
There's There's lots of things to be involved in. And as you said,
Katie, it's maybe something just to be mindful that you're selecting the right
pilots for the company, the program and the point in development that you are as well.
(21:30):
But I think today was a fantastic overview, really great insights from both
Katie and Julie in terms of what's going on in the regulatory space for 2024.
It would be great to be able to check in with you both at the end of the year
to see how successful some of these initiatives have been.
But for now I think it's probably a good point to say thank you very much for
(21:51):
for being guests on the show today I feel like I need to go back and listen
to some of those initiatives and take some notes for some advice but yeah it's
it's been wonderful having you both on the show today thank you very much for
your insights and we'll look forward to having you back soon.
Thanks Harriet. Thanks Harriet.
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(22:12):
Thank you for listening to Conversations in Drug Development,
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Music.
Music.
(00:05):
Hello, and a warm welcome to the latest edition of Conversations in Drug Development,
brought to you by the team at Boyd's.
This podcast is for our fellow community of scientists and clinicians working
in the wonderful world of cell and gene therapy and drug development.
Thank you for tuning in, and we hope you enjoy the conversation.
Music.
(00:31):
Hello, and welcome back to another installment of Conversations in Drug Development,
My name's Harriet Edwards and I'm your podcast host for today's episode.
Today's episode is building on the theme of our first 2024 episode,
where we discussed hot topics and trends to look out for in 2024.
This time, we'll be taking a deeper dive into regulatory topics,
specifically in the US, to decide what trends to be on the lookout for.
(00:55):
I'm pleased to say that today I'm joined by not one, but two of our senior regulatory
team here at Boyd's for today's discussion. discussion.
Katy Rudnick, our Head of US and Dr.
Julie Warner, our VP of Regulatory Affairs.
Katy and Julie, welcome to the podcast. Thanks for being here today.
Hi, Harriet. Thank you. Hi, Harriet. So I guess we've kind of built this podcast
(01:15):
episode as trends and things to look out for in 2024 with a specific focus at
the FDA because there's loads of interesting developments and lots going on.
So I guess that's a good place to start.
So Katie, after the ups and downs of last year, what's going on at the FDA?
Sure. Right to kick off the year, there are a few major changes.
Firstly, Janet Woodcock will be departing at the end of the month.
(01:36):
In her stead will be Nemanja Bumpus, who has been chief scientist since June of 2023.
Some of her main focuses will be on foods. And in her history,
she's done a lot to expand the cosmetic regulations.
So we'll have to see how this plays out for drugs. Another big change is that
FDA will be going through yet another reorganization. the Office of Regulatory
(01:58):
Affairs will be transformed into a new Office of Inspections and Investigations.
So many of the current offices will be impacted. However, the changes are meant
mainly to be focused on inspections, investigations, and import operations.
So the change is meant to help ship these compliance-related functions under
a better structure and chain of command for those activities.
(02:19):
So another objective of the RE-ORG
is to stand up a brand new Office of Regulatory and Emerging Science.
This does seem to be duplicative to the existing Office of Regulatory Science
and Innovation. So time will tell what functions overlap there.
Okay, so definitely something to watch out for, particularly if people are planning
interactions with the FDA, they may be going to a new office for those.
(02:41):
Yes, we'll have to see how that plays out. There is a nice structuring on the
FDA website, if anybody would like to check that out, that shows which offices are impacted.
Great. And then other developments, I know there's quite a lot of initiatives
that we'll touch on today as well.
Yeah, a few of those I can discuss in a little bit more detail.
So last year, We saw the introduction of several measures and schemes all across
(03:03):
the board with the CMC development and readiness pilot.
Also, the START trials initiative, which we'll speak to in a little bit.
We've also seen FDA's first thought paper on the use of AI in drug discovery.
And additionally, CDER initiative on innovative clinical trial approaches.
Interesting, both of these latest two items reflected on instances where the
(03:26):
FDA has said, please come talk to us.
We're looking for your feedback and your comments and input on what's important
as experts and drug developers. And then there's Operation Warp Speed as well, right?
Yes. So Operation Warp Speed was pretty successful during COVID-19 pandemic response.
And so the agency really intends to continue to utilize this moving forward.
(03:47):
It's a partnership between the HHS, CDC, FDA, NIH, and several other government agencies.
And it basically lit a fire under some of the programs to give enhanced government support. support.
So with FDA's focus on rare diseases, it's thought that this will be an area
of concentrated development and to move those programs speedily through the process as well. Right.
(04:10):
And there's actually a lot to unpick there. You've just mentioned,
just rolled off the top of your tongue, lots of initiatives.
And I'm sure we're going to unpack those throughout the course of the podcast
in a little bit more detail. But before we do, all of them sound very promising.
So I'm looking forward to hearing a little bit more information about them
but I know I have to say a nod to one
of the most exciting things that happened for me personally as
(04:32):
somebody that's keenly interested in genome editing was obviously
the FDA's approval at the back end of last year of
the first CRISPR-based medicine so that was
of course hot off the heels of the MHRA here in
the UK who were of course the first people to approve the first ever CRISPR-based
medicines are very exciting and I guess that brings us nicely on to thinking
about different territories and duly specifically the the EU it's been clearly
(04:57):
very innovative 12 months for the FDA as Katie's just mentioned it's the same
thing happening over in Europe?
Well, Harriet, I really have to take my regulatory hat off to FDA.
They've really pulled a series of initiatives out of the bag that will help
developers have an expedited dialogue with the agency when it's warranted,
when it's truly warranted.
So we have had some measures introduced in Europe. So we have the MHRA's Innovative
(05:20):
Licensing and Access Pathway and IDAP, the equivalent for devices.
But we truly haven't seen anything along the lines of what FDA is doing at scale in Europe.
And let's not forget, it's only this year that we've seen EMA
join Project Orbis which has been running since 2019 as
an observer and not actually even as a participant and this is maybe because
(05:41):
anything at the centralised European level just is so much more difficult to
coordinate with 27 member states being involved and all of the political and
legal backdrop that you know is behind that so I think it will just be interesting
to see how this plays out over time.
Yeah absolutely and I think maybe that's a topic of Another podcast is talking
about how the EU come together with 27 different opinions to form a centralised
(06:06):
sort of harmonised approach to things.
So watch this space for a different podcast on a different day.
But let's go back into the FDA initiatives, Katie, because we've mentioned quite a few of them.
And I think lots of interesting developments to talk about.
But maybe we should begin in the clinical trials arena at the start of drug development.
And maybe that That is a good place to start the START initiative. Exactly.
(06:30):
START is an acronym for Support for Clinical Trials Advancing Rare Disease Therapeutics.
This was initiated in the last half of 2023 as a pilot program.
So this engages more frequent FDA communication in hopes of resolving clinical development issues.
And Dr. Marks, the director of CBER, has seemed to really champion rare disease
(06:51):
treatments. and we continue to hear promise of more FDA efforts to assist sponsors in this area.
But START also crosses over into CDER as well with a slightly different qualifying
requirement set, but applicants can go ahead and sign up until March.
However, this is a very small pilot with only three INDs to be accepted under each center.
Oh, wow. So if you do get involved, then you're very lucky if you're successful in this application.
(07:16):
There are some other efforts though. Continuing on is the ARC program for or
accelerating rare disease cures.
And this does have a brand new offshoot called Leader3D. It's currently soliciting
rare disease drug program development information to fill knowledge gaps in
development regulation.
And the docket for this is open through the end of April. It's open to industry,
(07:37):
but also patient groups, academia, basically anyone who would like to submit to the public docket.
And FDA's wish for this is to create a publicly available resource on submitted topics.
It's a bit unclear what direct benefits are to be had by the stakeholders.
Other than just some general information on stumbling blocks or,
you know, areas of interest. So we're yet to see what comes from that.
(08:00):
And a different kind of initiative. I mean, the START program,
the pilot that you mentioned, there are obviously clear benefits for successful applicants there.
But it will be interesting to see how well received the ARC program is,
particularly with regards to whether or not industry want to share their development
programs and divulge maybe confidential information. So, yeah,
(08:21):
definitely one to watch to see how successful that is.
Yeah. And I'm really excited to see how the start pilot pans out as well,
in particular, whether it will have a broader scope than perhaps just clinical
items and whether it will help to take some non-clinical and CMC issues off
the table or whether you would still have to pursue those via other means such as CDRP.
But I guess, yeah, again, early days, we'll just have to see how that pans out.
(08:44):
It's really good that you've mentioned CDRP there, Julie, and I think maybe
we can come on to that in a moment. But just to continue the theme on clinical
trials, there is also an initiative by CEDA around innovative clinical trial approaches.
So, Katie, can you tell us a little bit more about what that actually means?
Absolutely. So FDA is currently in a data gathering period.
(09:05):
Basically, they're looking for general pros and cons to collect these of different
feedback bits to understand the pain points.
Is there are some innovative trial designs with newer elements,
new technologies, and these types of things also include real-world data,
which we've experienced for a while now, but AI.
And, of course, that comes in many different formats. So right now they have
(09:26):
workshops and listening sessions that are currently underway.
Comments to the docket close in spring, in April.
So FDA has acknowledged many times that they're always in a game of catch-up
with emerging tools and technologies.
And so they're cognizant that this information gathering step is the first step of the puzzle.
And following on with feedback sessions is their typical way to kind of stew over things.
(09:50):
And eventually they'll reach into a guidance writing period.
They have been extremely vocal about AI and just acknowledging that if you aren't
investigating it and putting efforts into incorporating it into your programs,
you're a little bit behind the curve already.
Yeah, and that's really interesting. I don't think that's specific to FDA actually
commenting that they're a little bit behind the curve in terms of development
(10:12):
of AI and developing regulation and guidance to support.
I think that's across the board and regular listeners to the podcast will remember
that we actually recorded an episode specifically on AI last year.
And actually half of the information or maybe even more is probably outdated
already because there have been so many developments in this area.
So Julie, you were on that podcast with me as well.
(10:35):
Any updates to how the EU regulators are looking at AI since we last talked about it?
Yes, a couple of big developments in December, Harriet, and is it really six
months? It feels like five minutes. I know.
We had a provisional agreement between the European Parliament and the Council
on the AI Act, which is the first EU-wide regulation on AI.
(10:56):
And secondly, the EMA's Management Board agreed to a work plan to 2028 covering
several really important elements on on the use of AI in drug development.
And that work plan recognises the incredibly fast-paced nature of the field
and that we need to consider significant elements such as data protection and
ethics and the need for consultation.
(11:17):
So we have had some movement and it's been really great, but I totally agree
with Katie. It just always feels like we're behind the curve on this.
Yeah, it's nice to know that Europe are not necessarily falling behind the US
on this one. It's just generally everybody's falling behind the speed of development of these technologies.
So lots going on in that space and lots to look out for in terms of how the
(11:39):
use of AI and other emerging technologies can actually accelerate clinical trials.
But of course, all of these things are only good if everything else that supports
the use and the initiation of clinical trials can also keep pace.
So just thinking out loud, really, about manufacturing, that has to keep up
with all of the other innovative things that we're doing around clinical trials,
(12:00):
study design and things like that.
So going back to what you mentioned around the CDRP pilot at the FDA,
that's specifically focused around CMC and manufacturing.
Katie, can you give us a little bit more information about that and maybe any
experience that we've had with this pilot so far?
Sure. Just to touch further into that. We're into the second year for the CMC
(12:22):
Readiness and Development pilot.
This is really nice because it does offer two specific CMC Type B meetings,
inclusive of follow-ups and different communications.
So the sponsor does have a direct benefit immediately.
The goal is a quicker CMC agreement for programs and accelerated clinical development
or an overall quicker product approval.
(12:42):
And everybody wants that, of course. We know of two companies to date,
both Bicycle Therapeutics and Raise Bio, have been public about their involvement in the pilot.
So we know that it's going on and there are some activities in this space.
So we just kind of have to wait a little while and see how that goes and what
else they're able to publicly share.
I have to say, Katie, I think this feels like 1-0 to FDA again.
(13:03):
Again, as previously mentioned, it may well just be down to the fact that,
you know, we have 27 member states to accommodate in Europe,
but also we have a slightly different regulatory approach in that we don't have
the cradle to grave system, you know, that there is in FDA with an IND.
So everything's a bit more disjointed from a European perspective.
So I think one area that it would be good to see this impacting on is the potential
(13:24):
for more global harmonization, which feels like it's coming,
but it's just going to take some time to come in. and we just don't know to
what degree it will, but it's a really exciting space to watch.
Definitely something to watch. And as you said, Julie, I think it's something
that will become more and more prevalent over 2024.
We have to make sure that particularly CMC development can keep pace with all
(13:45):
of these other innovative initiatives that are ongoing. So definitely one to watch out for.
Another pilot that FDA, just flipping back to FDA with all of their many pilots,
another pilot that had been recently announced, Katie, was the first iStand.
Pilot program for AI-based and digital health technology for neuroscience,
(14:05):
which is quite exciting as well.
Yeah, the agency has a few different drug development tool qualification programs.
These help developers with measures that aid in drug development and regulatory review.
We're talking about biomarkers, novel clinical outcome assessments,
and other different tools and technologies.
However, these programs are often specific, and so the I-STAND,
(14:28):
so the The Innovative Science and Technology Approaches for New Drugs,
to spit that all out, pilot program, is designed for those who don't fit the current programs,
but which still have great value.
So the AI-based entry into iStand is really exciting, as it is one true tangible
example of how rapidly AI is moving into the drug development space.
(14:49):
Different project using machine learning models to derive the clinician-reported
outcomes for, say, depression and anxiety. And it encompasses two key technologies
at the cutting edge of medicine, giving FDA the opportunity to really drive
regulation in the field.
I think this one particularly is very exciting because it builds further on
(15:10):
the docket and the innovative trial approaches that we were mentioning earlier
in the podcast to actually give something tangible and supportive to AI developers.
So I think personally, that's a really encouraging sign and something building
further on just guidance.
But that's quite unique, I think. Julie, is there anything similar in terms
of offerings from the EU? you?
(15:30):
Well, we have longstanding programs to help with qualification of novel methodologies
in their use in clinical trials.
And obviously, we have the routine scientific advice procedures.
But again, nothing specific along these lines that FDA has introduced.
But that leads me to conclude that this is really another goal in the net for FDA.
So I think it's clear to say that FDA are leading at the moment in initiatives, which is great.
(15:56):
And And I guess we've mentioned so many already.
If there can be anything else, what else is there? And actually,
there is something else to mention.
FDA have just announced a quality management maturity program,
and that's to incentivize drug manufacturers to go even beyond GMP,
so good manufacturing practice.
Presumably, Katie, that's in an effort to help address future drug shortages,
(16:20):
for instance, or something else. Can you give us any more insight onto that?
Yeah. Yeah, FDA's focus here is really on encouraging manufacturers to take
a more holistic and ingrained approach to their quality management.
It's early days here. This was only announced at the end of January,
and very few sponsors will end up being selected to participate.
But interestingly, the FDA has stated they plan to acknowledge these establishments
(16:42):
and kind of call out the successes.
So I'm not sure how this will be done, whether it's on a private or public scale.
But in the end, participants will have the opportunity to see how they measure
up against the other pilot companies in an anonymized manner.
However, they will get to see the outcomes.
And it's just a very interesting and different perspective.
Yeah, absolutely. And not something we typically see. So as you said,
(17:04):
very interesting perspective.
I think it's looking like it's going to be a very busy year over at the FDA
and perhaps even at the EU if they maybe want to keep pace.
Certainly as busy as it was in 2023.
I don't know whether, Katie and Julie, if there's anything else,
I know we've mentioned a lot today, but is there there anything else that we
maybe should be keeping an eye out for in 2024 any other activities,
(17:28):
Well, of course, these pilot programs exist and are in place,
which is great, but it will take a while for those to roll into regulation.
There are some apparent FDA kind of hot topics that they're pushing,
and those are rare drugs and further collaboration.
So we can look forward to different advances in those areas.
And a review of the 2024 legislative goals shows a focus on foods, animal products,
(17:51):
a general tightening up of regulations already in place, and of course,
considerations for future pandemic scenarios.
But knock on wood, I really don't see anything I would consider to be disruptive
to our current processes for the remainder of the year.
FDA's voice lately has basically been a positive influence to quicker patient
access and more frequent communications, advanced knowledge sharing up above
(18:16):
and beyond anything we've seen thus far.
And I think we'll see the typical drag times for getting these guidances caught
up to all the pilots and the different initiatives that are in place.
Yeah, and I think from the European perspective, we obviously know that the
revisions to the pharmaceutical legislation will be coming.
Yeah we don't know what and we don't know when because i
think the original proposals were quite far reaching and
(18:37):
quite a lot of consultation on those and there will be some changes
coming i'm sure but we just don't know when yeah topic for
another podcast i was just going to say the exact same thing
i definitely don't think we could cover that in sufficient time today but certainly
something to watch and yeah do watch this space we will cover that in a future
podcast sure and harriet there's one other topic here too there's potential
(18:58):
for ramifications of moving through
through these clinical development programs at an accelerated rate.
Of course, we want to give those our best efforts, but we also have to remember
we're working with a limited data set at this point.
So we shouldn't forget that FDA is vigilant, clear through the development program
and beyond into the approvals phase.
So we've seen a few changes here in that there is a recent black box requirement
(19:21):
for CAR-T products. Yes. And-
This is where they've requested very specific labeling requirements and additional
lifetime patient monitoring to patients in the immunotherapy trials.
So it just shows that there is active monitoring of all these things.
And although we're trying our very best to get these developments processed
(19:42):
through and get the science, you know, on top of things, we do need to be vigilant
and continue to monitor.
I can happily report this is one area where Europe is keeping up,
importantly. Certainly.
So we know that the EMA's Pharmacovigilance Risk Assessment Committee started
looking at the safety of CAR T products as well in January.
And obviously we are now around February time.
(20:02):
That review is still ongoing and should be concluded soon.
We don't know whether the UK MHRA is also looking at this.
They haven't published anything in the public domain right now,
but it wouldn't surprise me if they are looking at it too.
So I think it will be interesting to see how those reviews line up with the
FDA's position and how these products will further align as time goes goes on. Yeah, definitely.
Yeah. One thing to note here too, is that although the FDA has a virtual airport
(20:28):
full of pilot programs, it's not always going to be the best fit for all development programs.
So sponsors really need to take a look at their program timelines,
budgets, and different things, because with advanced communication.
There also becomes more busy work to do and it doesn't always fit the scenario perfectly. So,
(20:48):
take a close consideration, see what programs exist and see if you can leverage
those to benefit your timelines.
That's really good advice. And I was just going to say, actually,
I can't believe we've whizzed through so many different initiatives,
so many different things to look out for.
I honestly think, as I said earlier, 2024 is going to be a very busy year for
(21:09):
anybody that's going to be working in the US space, whether it be early clinical
development or whether it be later into licensure. There's lots to look out for.
There's There's lots of things to be involved in. And as you said,
Katie, it's maybe something just to be mindful that you're selecting the right
pilots for the company, the program and the point in development that you are as well.
(21:30):
But I think today was a fantastic overview, really great insights from both
Katie and Julie in terms of what's going on in the regulatory space for 2024.
It would be great to be able to check in with you both at the end of the year
to see how successful some of these initiatives have been.
But for now I think it's probably a good point to say thank you very much for
(21:51):
for being guests on the show today I feel like I need to go back and listen
to some of those initiatives and take some notes for some advice but yeah it's
it's been wonderful having you both on the show today thank you very much for
your insights and we'll look forward to having you back soon.
Thanks Harriet. Thanks Harriet.
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(22:12):
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