AbbVie Inc. ($ABBV)

Good day to everyone joining us, and welcome to today's Xtalks webinar. Today's talk is entitled EU clinical trial regulation, latest developments and upcoming opportunities. My name is Sonia Hunte, and it's my pleasure to be your ex-tax moderator for today. Today's webinar will run for approximately 60 minutes. This presentation includes a Q&A session with our speakers. This webinar is designed to be interactive, and webinars work best when you're involved. So please feel free to submit your questions and comments for our speakers throughout this presentation by using the question chat box, and we'll try to attend to your questions during the Q&A session. Now this chat box is located in the control panel, which is found on the right-hand side of your screen. If you require any assistance, please contact me at any time by sending a message using this chat panel. I'd also like to welcome our attendees viewing this presentation from our LinkedIn Live event, and I encourage you to submit questions as well via the comments tab. [Operator Instructions] Please note that this event will be recorded and made available for streaming to those who register on xtalkscom. At this point, I'd like to thank TransPerfect Life Sciences who developed the content for this presentation. TransPerfect Life Sciences specializes in supporting global development and commercialization of drugs treatments and devices designed to improve and save lives. Their comprehensive solutions include eTMF and eClinical technologies, paper, TMF migration, pharmacovigilance and safety solutions, translation and language services and cost center support. With offices in over 100 cities worldwide, TransPerfect is the ideal partner to ensure that your global line makes a global impact. Now it's my pleasure to introduce and welcome our speakers for today's event. And Pierre Omnes is also going to be my co-moderator, so welcome Pierre.

Hi.

He is the Executive Director at TransPerfect Life Sciences, and he has over 23 years of experience in global CROs and pharmaceutical companies. He is a subject matter expert in clinical trial regulatory operations and has been representing industry as an SME in the [indiscernible] initiative to develop the EU portal CTIS. Next, I'd like to welcome Gaby Di Matteo. Hello there, Gaby.

Hello.

So she is leading the EU level, the advocacy and strategic engagement on EU, CTR and CTS at Pfizer and works closely with regulators. -- industry associations and global teams. She is a part of the CTS subject matter expert and of the combined groups bringing an operational sponsor perspective to regulatory and policy discussions. And next, I'd like to welcome Scott Feiner. Hello there, Scott.

Hi.

19 years of experience in clinical trial disclosure. Since 2021, Scott has focused on CTS and the ETR and since 2024 has served as 1 of 6 EMA designated industry subject matter experts for CTS. And next, Andrea Seidel-Glätzer. Hello there, Andrea.

Hello.

She is the Managing Director of the noncommercial German network of coordination centers for clinical trials and KKS network office. She represents academia as a subject matter expert in the ongoing CTIS activities. Now with the introductions out of the way, it is now my pleasure to pass the mic over to my co-moderator Pierre. So Pierre, when you're ready, you may begin.

And welcome everyone to this [ webinar ]. The topic is your clinical trial regulation. This regulation in Europe followed by a roundtable discussions with my co-panelists who are all members of these CTIS initiative, where industry and academia representative collaborate with EMA in order to support the evolutions of CTIS, the EU portal in the future. So without further ado, let me start with the introduction section with a little bit of background on what happened in the last few years. So next slide. First, remember that the go-live of the clinical trial regulation took place at the beginning of 2022. And at that time, we had transition period, two transition period, one for submission and one for conductor trial, meaning we could submit under the old or the new system for 1 year, and we could remain under the old system for 3 years from go-live. And from there, several things happen, meaning that learning from experience, the system was upgraded, more guidance was published and pilots and initiatives were set up making this whole environment quite a dynamic environment, and we'll come back to that during the [ wrong ] table. So among the key milestones or event that took place, one could say that clarifications on what a patient document is and where it should sit in a submission came up in an update of the commission Q&A and impacted the content of Part 1 [ protocol ] section. We had, at the end of 2022, a revision of [ Anex ]6, which is the wealth labeling requirements are detailed. And this was a simplification to avoid concerns with the mandatory result of expiry date on primary packaging, which was quite rate limiting and in certain instances, at the beginning of 2023, we reached the end of the transition period 1, meaning that all submissions at that date had to go via cities, and there was no option to use the old system, you [ track ] anymore. During 2023, there was also the introduction of a workaround to allow for the submission of the quality documentation only when it's owned by a product owner that is different from the sponsor and there are confidentiality concerns. So that work around continues to this day. And it was also introduced by an update to the commission Q&A. The -- probably one of the main changes that occurred is the publication of the [ transparency ] rules because the [ CTR ] included significant enhancements around transparency. But at the beginning, it meant that all documents except site contract and IMPD were made public upon approval of the trial. But after the [ relaxation ] of the [ transparency ] this became only a set of documents such as protocol, protocol synopsis, recruitment materials, patient documents being made public instead of everything. So this relaxation of the rule had a very significant impact on all the proceedings and all the bureaucracy administrative work that was required in the background when preparing and submitting clinical high applications. This implementation of the transparency rules only took place in June 2024 affecting transition trials and things like that. But again, it took place. And now we are under those new rules and it made a significant difference, but we cover that also in the [ round ] table. If we go to the next slide, the updates continued. At the beginning of 2025, we reached the end of the transition period [ to ], meaning that all ongoing trials in EU are now exclusively sitting in cities and any trial that was still ongoing and not in CTIS had to be ended. So that took place. And this whole transition really kept us busy for most of 2024 and 2025 for those of us that had impacted trials. Then there were also, of course, during all that time, some upgrades to CTIS, some more minor fixing of bugs, et cetera, but more significant. And one [ such ] was the fact that when you were creating a trial at the beginning in CTIS, the creation of the trial includes the designation of a clinical trial sponsor, the main sponsor, and that sponsor could not be changed in CTIS once set up. In Q1 2025, the functionality to allow for the change of main sponsor was introduced in CTIS, which was quite significant. Again, the change of main sponsor is not a regular issue, but it can happen right often the acquisition or change of legal entities and different things. So that was a really welcome addition. It's a specific type of submission, but still now it's there and it helps. In terms of initiatives that were set up also to test the waters and to explore new avenues, the combined pilot is a good example where it was a test to see whether trials that included both a medicine component [ endoscope ] of CTR, but also some IVD in vitro diagnostic medical devices within the trial. That documentation could be submitted by CTIS and assess so that the decision could be given via one system instead of multiple ones. So that's somehow a test of something that we'll see is also a plan for the proposed biotech Act. The supportive documents on expanded. The commission Q&A we mentioned earlier was also updated several times. The clinical trial coordination group also issued its all frequently asked questions. So all of those different elements drive information for the sponsors and applicants to help them navigate the environment. And we see now a consolidation of the Q&A resources through three main ones. One with EMA that is more focused on CTIS, one that is more legal and legal interpretation or at least, yes, legal understanding that is the EU commission one and one that is more operational in a way and practical that is the CTIS [ CET1 ]. And again, come from many different Q&A to three main ones in the last few months, which is also a welcome addition. The implementation of an upgrade to the nonsubstantial modification functionality in cities, allowing for most document types, most documents and more structured data field to be updated via [ nonsubcentral ] modification instead of only a few in the past. Was also much welcome because it gives us more flexibility to amend over [ CA ] over time. And of course, at the end of last year, there was a long-awaited propose changed to the EU clinical trial ecosystem in Europe via the EU biotech proposal, which is a new regulation. And it came with other things pertaining to medical devices, in vitro diagnostic medical devices as well as [ genetic ] -- On the manufacturing sectors. Of course, among that, there are some specific elements that pertain to the proceedings of clinical trial management, clinical trial conduct and therefore, there are some impacts on the clinical trial regulation and on CTIS that can be expected. The goal being to make all this process faster, simpler and more predictable. And the predictability is quite an important one. If I was to summarize the Biotech Act, EU CTR impact in a few bullets, they are listed on the slide here. One of the most expected one is the reduced assessment time lines. The submission of [ all ] but there is a reference to mutually exclusive [ SM ], which will probably put some restrictions to the parallel submission nature that we would all hope for, but there are practical considerations technically that also with some limits to that. So the [ mutual ] it is still better than no parallel submission at all. There is the introduction of a minimal intervention clinical trial in addition to the low intervention clinical-trial status that existed in the original. Well, we'll see what we can do with that one. More importantly, there is a new concept that has been introduced in this biotech act proposal. It's the IMP [ or dossier ] and the concept of a deposit remember state, meaning that almost like when we commented and discussed with EMA, all industry and stakeholders, we were looking into something that looks like a little what the -- and then you have [ doses ] for each three, and that allows to manage the information and manage the modifications in a more efficient manner. So it's not an IND lag, but still, there are some elements of the IND that could lead to operational benefits on that side. But again, we'll cover that through the discussions. Expedite processes for public health and agencies. The combined study, INP/IVD is also introduced removal of the optional 5[ 0-dassessment ] extensions for [ ATMs ] reinforcement of the RMS whole possibility to change the RMS, the reporting member states. That coordinates the Part 1 assessment and also enforce collaboration and communication. So it's quite broad, but that is just all of those changes are only one article of the [ Biotech ] Act, Article 58. And so it means that the biotech app is much broader than that. It includes financial measures, incentives, all the clinical trial infrastructure is affected by that and aims to streamline the process. But today, we'll really focus on the [ C1 ]. And for the last slide, I will just conclude this to say that even since the beginning of the year, there have been further updates, meaning that the commission Q&A has been updated. On the EMS side, they have finally published this consolidated questions pertaining to CTIS into one source instead of multiple ones that we had before. And on the [ CCG ] website, they launched the [ Fast ] procedure, which is a test for the accelerated assessment timeline that are, in fact, also planned by the Biotech Act. And they also launched a new workaround procedure for [ Asia ] submission under Article 11 that looks promising. So a lot of things happen in that space. And as you can see, the last 4 years have been quite active and active. And so let's now go to the [ home ] table discussions with our panelists to discuss a little bit about the different aspects that of those 4 years and what's coming up.

So thank you all for joining. I would be interested first to get your impressions on those last 4 years. And what did that mean for you on the trial execution standpoint, particularly when the initial launch of CTIS was really a minimal viable product, and it was clearly labeled by EMA. And I don't know, Gaby, do you want to start maybe with how you look back at that last 4 years?

Yes, I can certainly try to bring my point of view. And yes, it was nice for back years, and it was nice to be part of the [ game ] in the beginning, but it came with some challenges. And it was very well welcomed as a new system, but it came with some hurdles as well. The first point we had to put in place was training and change management for the teams. It's not always easy because while we had you [ drag ] and the content of the [ dossier ] can be very much compared to [ our ] drug, but the system, of course, is totally different. So we had to put in place trainings. We have the trainings that we created by EMA, which were very nice trainings. But as I said, we welcome very much the sponsor handbook, which is grouping everything in one place, which was not the case at that time. And so in Pfizer, for example, we made a choice of creating our own training environment with supporting documents, screen shots, et cetera, to make sure that we didn't have to go in different places for each step of the submissions. And ensuring also that all people are trained in the same way and understand it correctly. And I won't say, see the limitations because the limitations were changing every day or every other day when submitting. So yes, it was interesting and challenging times at that time, but the result was worth having just one ddossier for all regulatory bodies were something very positive as a minimum. And having one dossier for each member state was also very positive, but we had to adapt to each countries also.

Yes. indeed and even the fact that it's switched naturally to all electronic and no paper submissions anymore was also a kind of secondary benefit. Scott, on an industry perspective, anything to add based on your organization experience regarding those [ 4 years ] and how you navigated them?

A couple of things. Of course, the change management that Gaby clearly outlined already. But one thing we were doing at the beginning, too, is really adjusting for the original transparency rules, right? At the beginning, we were basically saying, any document, any free tax, just assume it's going to be disclosed because that's the way it was situated. So there was a lot of infrastructure that had to be built to support redactions, quick redactions for RFIs. So that -- yes, yes. And for -- from the [ trialisclosure ] perspective, it was really a huge shift. And of course, this changed on the 18th of June 2024. But that was a big part of our original learning. And also at the beginning, sometimes the RFIs wouldn't submit somebody is going through it. Like I'm trying to submit my RFI, it's due in 2 hours, right? And you would go and raise a service desk ticket. That pretty much is all behind us. But at the beginning, that was very much something that you had to be on top of. Every time you're doing this mission, you is going to go through, is there an error? What do we do next? And we're way past that now, which is I'm very grateful for.

Thank you for that. Andrea, I'm also interested to get your take on the -- on those last 4 years on an academic standpoint. And I think the -- well, the change management might be slightly different in your case.

Yes, it was probably very different. And I think we had really high expectations on the harmonization and everything, and not everything came out the way we wish for it, because -- it was planned to foster multinational trials for academic sponsors, and I think we are not there yet. So we are still working on it. But for academic sponsors, the sheer amount of information and things to learn was so big that a lot of people were really afraid to do submissions in the beginning because it was so much, as you said in the introduction, very much information, very much documents, documentation that was new, new portals like the XEVMPD which we have never used before, but now we had -- we were forced to use it, and we have to build -- still have to build some expertise in these fields because we don't have special department for these things, we have to do it all on ourselves. So that was really a big change and really a hurdle to keep this all in mind to know all the workarounds, to know all the things that we have to do and not do. So that was really change management.

No, [ Remy ]. And I note that none of you mentioned the whole topic of transition trials, but it's done and dusted, all managed. So happy to have that behind us and not have that as an extra concern. If you were to select one or two, what would be really the main cities improvement that you appreciated the more that make the most difference in the last 4 years. Just a quick poll for all of you. Scott, do you want to start? I know where your heart may...

My first one is that revised transparency rules on the 18th of June 2024. It reduced the workload dramatically. And it pushed forward the protocol to being disclosed right away as opposed to the deferral of 5 or 7 years. So that mean -- it was great for all users. And frankly, I think the other thing is the [ Article 81.9 ] that went live on the sixth of November. Being able to provide updated Part 1 documents in 19 is just so helpful, and it's reduced or eliminated, right, some part 1 substantial modifications, where you're not only waiting you're paying fees, right? So that -- both of those are the top of...

Yes. The non substantial modification is what we mean by Article 81.9, but that time was also a really good one. Andrea, on your end, anything in cities that made a significant difference in the last 4 years for academia?

Yes, I can just agree with Scott because the transparency rules, the change really reduced the workload on our side so much. So this was really, really a good thing to do. It's The best experience we had. And yes, we hope -- we are looking forward to the next one, which will hopefully be the e-mail notifications whenever they come. And this might be good improvement with all the limitations that might come with it.

E-mail notifications of the notices [ and ] are generated by cities. But June has a potential date. Gaby, anything to add on those improvements that you really acknowledged in the last 4 years?

I agree with Scott and Andrea, that was very, very important. But I would add also the increased alignment among the member states because in the very beginning, there were very different points of views and many questions which were not aligned to CTR tax and requirements. And it took a bit of time, but I think we have to be very grateful for the creation of [ Medco ] as well who brought the voice of sponsors and who helped us understand or helped us explain and make the ethics committees and member states understand the hurdles from the sponsors and academia, I think.

Yes. And we'll come back to that, but I think that the whole ecosystem of initiatives and forums for sponsors and member state ethics committees and regulatory authorities to exchange and identify issues to find some potential solution is quite significant. We [ can ] act initiative, accelerating clinical trials in Europe. That's the meaning of the acronym. We can talk about combined [ Meditec ] CEO the work that is done by the clinical trial coordination group is quite significant also in terms of streamlining, underlining regulatory authority positions, and they collaborate also with -- so we have a collaboration between [ Etix ] and regulatory, the created assessors on table to build that alignment. So all of that is quite welcome and will bear fruits. But well, it takes time. That's the one thing that I can say. If we were to focus on the two, three elements that were still your main remaining hurdles, what would be the things that still need to be fixed? And maybe some of them will be fixed by the BTA. Some of them may still require some specific solution. But for you, what are your top 2, 3 hurdles. And Andrea, do you want to start?

Maybe one of the biggest hurdles for academia is still the [ IMPDQ ] application. It needs some improvement, I guess, and I would hope that the Biotech Act with the [ courts ] will change things for us because it needs a lot of coordination and communication between the collaboration partners. And yes, we would really appreciate if this would be a little bit easier because it puts a lot of workload on the academic sponsors, but we need the collaboration with industry and so it's really important for us.

Yes. Scott, on your end?

Certainly, [ Taplast ] is the Part 1, Part 2 alignment or misalignment that we have, where you get these parts on questions request for information, which impact your part 2 documents but you run out of time and you potentially have to submit a substantial modification before you can give recruitment to update those part 2 documents. So I know this is being addressed with the biotech Act. So looking forward to that as being addressed and that will just save a huge amount of time. Otherwise, there's a few other things, but that really stands out to me right now, and I'll let Gaby go.

Yes, Gaby, on your end, what's your take on the hurdles that you still

I would add one or two points to that. One of them is also document management because when it comes to filing in our TMF, it's not very easy to have a comprehensive and easy list of documents. So we manage with work around, but it's a lot of time. So we heard that it will be coming. It will be improved in the future that we -- and we -- we hope it's a near future. It will be very, very welcome. And -- also with that, we spoke about it, and this will be sold by Biotech Act is the sequential submissions. So parallel submissions of substantial modification is also a hurdle. We know it's coming now, but we still need to be patient before it's implemented. But yes, it's still one of the big hurdles that we have at the moment.

Related to that, I think Article 11 helps a little bit in this regard, where right now, we're running into either at a member state or an update Part 1, right? So if we can start leveraging the Article 11 work around, sorry to jump ahead. that helps us, I think, even before the Biotech Act have a little bit more flexibility and get to faster approvals.

Indeed. And of course, we mentioned earlier, the lack of member state harmonization that is still present on a few topics, but that tends to reduce. And I think it's more of -- well, does not impact everyone, but we discussed that also in our preparations. But the operationalization of complex clinical trials in CTIS is quite a challenge because if you have several trials or one master protocol with ancillary one, putting all of that with either the misalignment, the sequential [ mission ], et cetera, it makes complex in [ call ] still quite a beast to manage. But still, guidelines have been published, issues have been identified. This is on demand. So we will see how it transforms, but we also need to account for this complexification of the clinical trial protocols and how they can be operationalized into an IT system. Thank you for that. Just one quick question maybe after the -- this background on those 4 years. Maybe one last question on -- I suspect that some of your organizations, I hope I expect, were quite significantly involved in readiness initiatives prior the launch of the CTR. Retrospectively, do you think that your readiness efforts [ both ] fruits? Or were there things that you had to [ course ] correct because it was not as you expected. So how do you look back at the readiness and the situation urine and whether it was indeed relevant to go with such an extensive initiative if it took place in your company. Scott, do you want to start? I see you [ is ] thinking about it.

So one thing I would do differently, but looking back, we were trying to be as specific as possible before CTIS was available, right? So in 2021, right, we're trying to prepare people and trying to be specific. But then when CTIS actually launched, right, there are certain nuanced details that really impacted what we have been providing for training, and we had to adjust them. So I'm thinking for the biotech act, right? I would be a little bit more high level at the beginning with the expectation that we are going to provide you basically real time or close to real time further details once we see the system in action. So I think that's one thing I would do differently. A little bit less granular detail before the system changes happen and then when the system changes happened, that's when we give you the full details.

Yes. Gabi, on your end?

Well, I thought we were correctly prepared and as opposed to Scott, we try to provide details to the colleagues before the system went live, so that they didn't feel totally lost the first time they would see the system. So we're prepared documents with green chart explanation, step-by-step initiatives and so on. But anyway, when the system goes live and you are facing a technical issue, a technical [ leach ], no can't submit because -- last [ said ], oh, to submit my RFI, but the system is blocked, and I can't go through. That's interesting situation. But yes, I think on the overall we were not too badly prepared. But when the system goes live, of course, you test it on a different angle.

Yes. Just to clarify, we had those details, and then we had to go back and fix some of them, right? So that's where -- just thinking...

The [ BT ], you're thinking that probably you will not plan and expect everything already and maybe see how the operational implementation looks like before...

Yes, at least say this is what we think it will be, but we will update you once we see the live versions, just so people aren't, "Hey, wait, you gave us this training. Why is it different now? Just to set expectations a little bit.

And there were many updates.

Yes. We could spend an hour on the management approach and how you set yourself up to monitor all those changes, but I think we'll move to other topics. Andrea, on your end, I think that probably on the academia side, the readiness might not have been heavy as large organizations, in particular, but still, what's your take on the readiness versus the operational execution during those last 4 years?

Yes. To be honest, academia hasn't been prepared very good for this, but we tried our best, I think. And like in Germany, I did a lot of work from the CTIS from the group, and I tried to teach. But it is very hard to do it for all academic institutions because there are so many different ones and some are organized, some are not. So this was really hard to get prepared. And I think, as I said before, a lot of them waited. Just waited what will happen and then started a little bit later, and I think that worked out fine. Although we still suffer from some things like naming convention in the beginning when we did transitions and just named documents, the way we still work with these wrong namings and it's still just causes confusion. So waiting was a good idea. And as the longer you waited, the base you got out of this. So yes. It's okay.

Yes. we all survived.

We never got ahead of the waste. So.

Good. [ To ] the current environment and specifically to the ongoing initiatives. So we are talking about [ CUMed ] which forms for et cetera, but we're also talking about pilots such as combined fast combined for the drug device well, IVD combined submission, fast, which was launched on the beginning of the year to -- which seems to deliver at a small scale, but with a full time lines in the range of 70, 75 days. So that's still an improvement compared to the 100-plus days that we've been seeing as a median in the past. There are also many workaround procedures. We talked about [ IMPD ], Article 11 partial submission. Those initiatives improvement that are not technically implemented that can be work around, et cetera. How do you perceive those initiatives in light of your daily operational activities, meaning do you make use of them? Do you see them as welcome opportunities, welcome improvement? What's your take on that?

I want to very quickly start with combined because, I mean, both groups as well. And I think it's an important initiative because when -- well, today, when you have to submit both under CTR and the IVD you may have your pharma study approved very quickly, well, in the usual time frame, for IVD or MD submissions, you have to rely on each individual national submissions. And it can be very quick for some member states and very slow for other member states. So combined having one single set of time lines, is going to change the life of these type of submissions, I would say.

Yes. And it's a feature of the Biotech Act proposal. So that's good that it's been tested and that the result seems to be encouraging enough that they really well. kept it and will enforce via a stronger framework and a stronger technical implementation.

Using CTIS for both is also very good.

Yes. Indeed. Andrea, on your end?

Yes. From academia side of you, we welcome all these initiatives and like combined is very important for us, too, because we do these projects. But like Fast EU, which is a very good initiative, I think, for the attractiveness of the EU is not that important for Academia, I would say, because I think, so far, no [ Aconex Ponta ] has applied for fast EU. And we still have 70% mono national trials in academia. So it is not that important to speed up these time lines, and most countries have already started to announce shorter time lines for the mono national trials. So -- but it might be a good way to foster multinational academic trials to make a little bit quicker.

And Scott, on your end? What's the -- what [indiscernible]

So it's interesting. So for FAST-EU, just the details that were announced have been interesting in preparing, right? We see the shorter RFI time lines. We also see this that the member states and ethic committees are trying to keep all of their tasks on the same day of the week, right? So that kind of early progress. So knowing what we're going to be in for with the biotech Act from the FAST-EUs kind of informing how are we going to provide these redacted documents much faster, right? What's the workload going to be? But in terms of day-to-day, some applications and such. But again, there's only 15 studies so far that are in FAST-EU. So it's not -- in 2026, this is not something where a sponsor is going to put 5 or 10 studies and have the faster approval. It's more of the lessons learned.

It's one by sponsor, and it's mostly a testing ground for member states to prepare for the BTA time lines. But still, it's an important one. And I think one of the main tasks of the industry at this stage is to scale up the FAST-EU as quickly as possible or to get the biotech act timelines implemented as quickly as possible.

So one other thing that it's related. But the pre-CTA advice has been very helpful for us, especially in complex clinical trials, really understanding what approach are we taking with multiple EUCT numbers? What does that look like because there's a lot that goes into it's almost like two submissions, right? If you have to submit under two UCT numbers, there's a lot more to consider. And the pre-CTA advice, we've leveraged that quite a few times, and it's helped us a bit.

Yes. The pre-CTA is a kind of a technical advice to organize the submission strategy in terms of content, splitting the submissions or not, et cetera, and that's one of the pathways that you can consider before to prepare your submission. I see time is running, so let's continue. And I remember everyone that if you have questions, please put them in the chat box, and we'll address them in the Q&A session. Let's go a little bit to conclude this from table around the Biotech Act at sales. And I think that the few things that I would like to ask you is this biotech at proposal. And again, it's a proposal, meaning that like any other regulation in Europe, it needs to get alignment between the council, the parliament and the commission and that's a procedure that's going to take time. What we saw as a proposal may not be the final results, and there will be evolutions. But still, based on that proposal discussed in December, which measures captured your interest and which really you would like to see implemented. Scott, do you want to start?

Okay. I mean the parallel substantial modifications that is very helpful. the shorter time lines, like we discussed, it's really going to be helpful. And the substantial modification time lines are even more compressed. So all of that, I think we're really looking forward to. But in our conversations, right, we're also being mindful of when will we see this change, right? We don't want to overpromise and plan that even in 2027, we're going to see this because we won't with the biotech act. But that -- and the core dossier is very interesting, too, but I'll stop there because I could just go on for a while.

Gaby, on your end, what are the ones that captured your interest and make your dream a hope for the better future?

I think to what Scott is saying my list was the short and time lines. But yes, of course, everything is interesting. Another interesting point and hoping that it will be doable and technically doable is that the fact that Part 2 conclusion will not be submitted before Part 1 conclusion is coming. It will save a lot of time and effort, say, meaning that we will not have to systematically submit a substantial modification to implement the changes from Part 1 when the Part 2 was already locked by the member states. So that's one additional point, which is very important, I think. And also the fact that we want all member states and be better aligned and having a BTA much clearer on what is expected, what is not expected.

Andrea, on your end? How do you see the EBITDA and its impact on your operations?

The quarter might be an evolution of the IMPD Q. I hope for that, that this will help and also what caught our attention is the additional risk category, minimal intervention trials. But so far, causes a little bit more concern than -- because we don't know what's behind this. There's -- it's very so far designed at a case-by-case assessment by the member state and this might open the door for a very different assessments and very different objections.

Yes. It raises a context of harmonization between member states and how they categorize that we know exist already in defining what is observational versus international. And personally, I'm also not sure that adding a category minimal in addition to low is going to improve things. For me, it's complexifying the environment, it would be better to have a minimal that works. Low intervention clinical trial [ sites ] that is better defined and works well to address the different cases than multiplying the categories. But well, we'll see how this is retained or not and what it will become in the final text. Just on -- to conclude with the final question, we saw from the EUCTR go live that the theory and the reality between the text and the technical implementation, well, might not be fully aligned or may take time to reach alignment I suspect, from what we discussed in the past few minutes that we might have quite a similar concern with the operational implementation of the BTA, its implementation, key how long it's going to take. The one thing I would like to mention is that interestingly, there is one in the BTA itself, there is mandated action for EMA to provide a plan for implementation of the BTA change 1 month after the vote of the BTA itself which kind of forces for an accelerated implementation. And the other thing that we can comment all SMEs on this call is that the discussions and consultations on how the BTA will be implemented already started. So the plan is really for the time to set up the BTA to be longer. But maybe one final word from each of you on -- how do you foresee this new period with the new techs coming up and whether or not the technical implementation will be aligned in a timely or functional manner. Gaby, do you want to start?

Well, I would say that if I could, I would compress time lines but we know it takes time to review. But yes, these changes from the BTA have been expected and long awaited. So -- we know it will not be perfect, and we know that the tax will change before it goes live. But in the meantime, we would like it to go live very quickly whenever possible, but we know well. We need to be a little bit patient. But please, member states and parliament, et cetera. If you can go quickly, we will be very happy.

I think that's the goal. And it seemed that the prioritization of the biotech Act impact on the CTR among the first thing in order to sort out the CTR impacts, the impact -- different impact on CTIS in order to accelerate the implementation of that. So the commission is also pushing for that. EMA is already working on it. So we can but [ hope ]. Okay. Thank you all for those thoughts on these different elements. Let's now take some of the questions that we received from the audience, and let's move to the Q&A. [Operator Instructions] And I will start with one question that is around the -- well, at least it's one that I will address already regarding the current foreseen time lines for the Biotech Act implementation. We don't know. But as I said, there is a negotiation process that is taking place between member states and that will take some time, probably a few months, ideally, it may be completed by the end of the year, but that's an extremely optimistic scenario. More probably, it will be during sometimes during 2027 that we reached that. And then within the Biotech Act itself, there is even after the vote on the publication in the official journal for everything that pertains to CTR, there is an implementation time frame of 6 to 9 months. So operationally, we won't see the -- all the improvements of the Biotech Act probably until at best second half of 2027, but more probably sometime in 2028, and we will need to monitor very closely the progress of the negotiations to see how this goes. But yes, that is really at the moment, it's mostly guesswork, but we know that all stakeholders on the regulator side and commission, in particular, are really pushing to get through those negotiations as quickly as possible. But again, EUCTR is but one article of a very long text and there are a lot of other measures that will require alignment before the [ taxes ] can be voted. And there was a question under the Clinical Trial directive, member states had the choice between approving or asking clarification modifications and there's the CTR. It appears that the RFI process has become automatic, even if there are no real objections to studies, adding significant time lines to the approval most approval requires a full 90-day period or even more. Do you agree and what can be done to encourage approvals in absence of field objections? Gaby, do you want to take this one?

Yes, I can. Yes, I can, certainly. First of all, I would add -- I would start by saying that I will not defining what is real objection or not? Because I get that the questions which are raised either by [ Rothwell ] always seem very important to them, and I respect that. I would like to put it in perspective because today, it is true that they take generally the full time line that although I think it improved. Well, it improved since the beginning. But on the CTD, we had one array, one EC and one local EC. Everyone was approving at its own pathway, I will say, and with their own time lines. And so in the end, from the first country to the last country, approving the study, you could have a very strong time line and much more than the 3 months that we have today, we need to take into consideration that the approval that we have even if it seems to be long and sometimes it is, but when you have your approval, it is valid for all member states at the same time or very few days apart from each other.

Consolidation of those things. Yes, indeed. Thank you. Anything to add from the others? Or do we take the next questions? Let's move to the next then. Removal of the 50-day ATMP close is nice for sponsors that it makes time lines more predictable and shorter but how our authority is going to be supported in their assessment in those complex modalities. Will there be designated RMS focusing on ATMPs? Scott, do you want to start with that one? And I might talk quite a few things.

And this is my impression, but I think the member states are much more comfortable working in CTIS and assessing. And so they didn't seem to fight this removal of the 50-day cause in the Biotech Act. I noticed at the beginning, sometimes even things that weren't designated ATMP still would get to 50 days. This is early on or 10 days because they can split it. I think the assessors are just more comfortable. They will split things if it's like a chemical or a biologic, right to certain assessors. But I don't really see this as being an issue any longer because if it were, I think the member states would have objected and raised concerns and I haven't heard that. So that's my impression here.

And if we look at the ATMP environment, I think that also the SSRs are much more comfortable now with the ATMP, meaning we are media with gene therapy and other things like that. So what in the past required an external expert involvement, that involvement of experts from the outside is much less required in practice, which means that I don't foresee that there will be designated RMS focusing on ATMP, [ visit ] will probably not be published. It could be that for certain very innovative products than the scientific capability of the potential RMS will come into play for the selection. But again, it could be better in the future environment, particularly with the Biotech Act, but plans to streamline the RMS selection for those very complex trials, it could also be relevant for the sponsors to pre-identify their RMS before submitting, and that's what the authorities encourage you to do. Already identify your RMS, if you can, and that will allow them to prepare and really to also be ready for complex assessments, et cetera. So by collaboration with the member states, we can also cope with that. But I think it can naturally this extension of time lines close is not really being used much more at this stage. Two questions that we could take together, and I will provide a quick answer. Will CTRS ever connect to other systems tubes like [ sarin ] and the other question was when do you think fully automated submission by bots or AI will be supported in the CTIS system? No clue is the short answer. Let's just say that there is an ongoing discussion since 1917 around the possibility to have sponsor APIs, application programming interfaces that would allow sponsor systems such as [ Viva ] and others to connect with CTIS. The idea at that time was that there would always be a manual intervention, meaning that even if you can automatically populate an application from your system, through CTIS, the act of submitting would still need to be done in cities itself. And so by extension, saying that boards or AI to be to populate CTIS it's not even in the road map. At the moment, could say that based on what all the road map before the BTA looked like, the sponsor API was a topic that was reintroduced in 2025 with a potential implementation date of '27-'28, but with the whole biotech all the modernization planning is going to be revised and presented to the EMA Management Board in June or well, before summer. And so we will know exactly whether the sponsor API and this modernization can be tackled. At the moment, I don't foresee it in the next 2 years to be wrong, but we can't provide you with a definite date on that. There was one question on ability to export initial emissions include only new information instead of exporting all documents. Gaby, do you want to take this one?

Yes. I mentioned document management, which is in the future improvements of cities, and it is something which will help tremendously for that. So the information we have so far is that we will be able to export the list of documents that were submitted either in Excel format or even PDF, but we will be able to cherry pick, I will say what we want to defer submission. The third one, the draught you're working on. So yes, it will make our life much, much easier. We still don't have the official go-live date? That's the other question. But it's coming, and we are all very happy that it's coming.

Maybe one last question, and -- do you expect any significant changes to the CTIS transparency rules, for example, justification for CTIS reduction? And I think this 1 kind of derives from the police [indiscernible] space. Scott, do you want to take that one? I know transparency is close to your heart.

Yes. And then we tie -- but generally, I wouldn't expect this. There's been so much discussion with the new transparency rules and I think this is fairly settled. Where this question, I think, is coming from is [ Policy70 ], the EMA, right, is still requiring you to justify your CCI. But remember, in CTIS, the EMA is not reviewing your redactions. It's the member states. So the member states would need to build a process to be reviewing CCI more closely, and I'm not seeing that. So for now, I don't expect to change, certainly not the next year or two.

Thank you, Scott. And I think we are close to the time. Next changes to be introduced in CTIS this year. Annual safety reporting module in Q3, e-mail notification for the notices on and by June. Those are the two main things that are expected for this year. Sponsored user metric change are probably more for 2027 and not for this year anymore. With that, I think will close the Q&A session and Sonia, back to you.

Well, thank you very much, Pierre, and Andrea and Scott and Gaby. I thank you very much for answering all those questions. Yes, we have concluded the portion of the Q&A portion of the webinar. For those of you interested in hearing more from TransPerfect Life Sciences, you can register for the next webinar. [ NPA ] labeling workflows that reduce relabeling risk and start-up delays scheduled for Monday, June 8, I put the link in the chat box, so it makes it easy for you to go ahead and register. Now if we couldn't attend to your questions, the team at TransPerfect Life Sciences may follow up with you after this presentation. And if you have any further questions, please direct them to the e-mail address, you see there on your screen. Thank you, everyone, again for participating in today's webinar. You will be receiving a follow-up e-mail from Xtalks with access to the recorded archive for this event. A survey window will be popping up on your screen. Your participation is appreciated as it will help us to improve our webinars. Additionally, I have shared a link to view the recording of today's event in the chat box, which you can share with your colleagues, [indiscernible] register for the recording here as well. And for those of you watching via LinkedIn Live Events, we encourage you to visit xtalks.com to register for this event and gain access to such features as viewing the recording and more. Now please join us in thanking our speakers for their time here today. So thank you very much, Andrea, Scott and Gaby and Pierre for being my co-moderator. We hope you found this webinar informative. It has been my pleasure to be your webinar moderator. On behalf of the team here at Xtalks, we thank you for joining us. Until we see each other again, I am Sonia Hunte. Please take care and bye for now. Bye, everyone. Bye, Pierre. Bye, Andrea. Bye, Scott. Bye, Gaby.