Hello everyone, welcome to today's broadcast, European Clinical Supply Planning: Balancing Cost, Flexibility, and Time, sponsored today by Catalent. Catalent solves today's clinical trial supply challenges and develops innovative solutions for the future. Their commitment to quality and service excellence is evident in its comprehensive and flexible solutions for small molecules, biologics, and advanced therapy medicinal products. With modern global facilities, Catalent has over 25 years of experience reliably supplying thousands of studies of all sizes and complexities around the world. I'm Jeanne Linke Northrop, Managing Editor with Pharmaceutical Technology. I'll be your moderator for today's event. Before we begin with today's discussion, I just have a couple of important announcements I'd like to make. First and foremost, this webcast is designed to be interactive, and so we encourage you to ask questions to our great presenter throughout the event. You can submit questions to her by typing them in the Q&A box that can be found at the bottom of your video player. You can also enlarge the slide window by clicking on the small icon in the bottom right corner of your media player. Please note, however, that all slides will advance automatically throughout the event. If you do happen to experience any technical problems viewing or hearing this presentation, please click on the question mark help widget located in the top right of your presentation window. In today's webcast, Dr. Claire Quinn joins us to discuss the critical factors that we see influence optimal placement of clinical supplies throughout Europe. Dr. Quinn is a Clinical Supply Manager at Catalent. She's responsible for end-to-end clinical supply strategy, forecasting, and support, including IRT setup and inventory management. With over 20 years in pharmaceutical industry roles, her previous roles have included preclinical research, lab testing, and clinical and commercial packaging. Dr. Quinn, thank you so much for joining us today. It's such a pleasure to have the opportunity. Feel free to go ahead and begin your presentation. We're looking forward to it. Thank you, Jeanne. Hello everyone, and welcome to today's webinar, during which we will be reviewing European clinical supply planning and the options available to support balancing the cost, flexibility, and schedule for the right strategy to meet your clinical trial requirements. Through the course of this presentation, I will be talking through the differing complexities of clinical trials and some of the things we need to think about when deciding the best supply strategy. We will be considering the geographies of the supply chain with particular focus on Europe, looking at logistical approaches through Europe, including non-E.U. countries such as the U.K., and also considering other aspects of clinical supply which are key contributing factors to working out the best supply strategy for your trial. First of all, to provide some credential to the presentation, I would like to provide you with some background on Catalent as the presenting party today. Catalent is a world leader in reliable clinical supply services, with extensive experience and expertise to support even the most challenging of studies across the globe for sponsors of all sizes. Catalent offers innovative supply models, integrated solutions, and specialized services to provide the optimal level of flexible support from early development and manufacture through all clinical trial phases and commercial supply and beyond. We very much foster a patient-first culture, and our patients are always at the center of everything we do. It is this latter point that really drives the passion we have to reliably supply comprehensive solutions with flexibility and speed across the world. So, where to begin? Clinical supply strategies begin with the Phase I study, usually at that early stage, without a huge amount of thought into scaling up for later phases. So, it is worth taking a moment for us to remind ourselves of the increasing complexity from Phase I through to Phase III-A, Phase I study is typically a smaller number of subjects being treated for a short duration at only a small number of localized clinical sites. A Phase II study is typically up to several hundred subjects, with the target disease or condition being treated over a longer period, anything up to a couple of years, and involving dozens of clinical sites across multiple regions or countries. A Phase III study then scales up even more, typically several hundred to maybe thousands of subjects, with the target disease or condition being treated for an even longer period, up to several years, and takes a more global approach, with hundreds of clinical sites in multiple regions and countries. If we look at Phase I a bit more intently, this is usually a blinded study, sometimes with complicated dosing schemes. While there is usually only limited stability data available at this stage, the shelf life of the drug product is typically not an issue due to the short duration of the subject treatment. Packaging of patient supplies is often tailored to the Phase I requirements in terms of unit dose and subject visit schedule. It might be that there is a low volume of kits, and/or there are kit type variations. It's important to remember that the cost per patient kit in a Phase I is generally higher, and that's driven predominantly by the low volumes being manufactured and then subsequently packaged and labeled. There is often an unblinded pharmacist to manage the randomization of patients and dispensation to patients, as opposed to using an IRT. If we look at Phase II studies, we immediately get a feel for the scaling up of activities required. Phase II studies are typically dose-finding studies, often with titration or dose escalations, and complicated dosing schemes with multiple doses and treatment arms. Blinded packaging is often required, and an IRT is used because it's no longer feasible to have an unblinded pharmacist at every site, given the larger number of sites involved. The duration of the study will often exceed the shelf life of the drug, so multiple packaging campaigns should be planned, and/or expiry update labeling may be required as more stability data becomes available through the course of the trial. A Phase II study will expand into multiple countries, and depending on which countries they are, there may be varying regulatory requirements for import and export. There may be specific stipulations on the clinical trial label, specific release requirements. When we look at a Phase III, consider all those same challenges of a Phase II and amplify them. We have more countries, more patients, longer duration of treatment. There is particular focus on scaling up in terms of both manufacture and packaging and labeling volumes. Retest dating may still be a concern. Now, stability analysis will be ongoing, so the earlier you set down stability samples, the better. But generally, you will still need to think about that retest date and plan accordingly around it to ensure uninterrupted supply to your patients. Depending on the clinical trial scope, you may need to include comparator arms, which in turn introduces sourcing challenges and packaging and labeling requirements to ensure blinding. The overall supply chain becomes a lot more complex, with multiple depots now. You have to think strategically how best to ensure supplies can be maintained in terms of storage condition, and you have to think about end-of-study activities in terms of reconciliation of supplies. It's worth noting that while I have broadly split out considerations between Phase I, II, and III here, some of the points highlighted may be worth considering across multiple phases. Comparators are not unique to Phase III, for example. There are open label trials, crossover trial designs. Some earlier phase trials will use an IRT, for example. But hopefully, I have demonstrated the mindset that we need to scale up from a Phase I. So, where to place clinical trial packaging and labelling? In theory, this could be done anywhere in the world, with providers located across the globe. But in reality, we need to tailor our approach based on key considerations for the clinical trial. We need to think about where the drug product will be manufactured, where stability and other key analytical test sites are located. Are there any special handling or storage condition requirements for the drug product itself? How many clinical trials will participate in the study, and where are they located? How many countries are involved, and what might that supply chain look like in terms of logistics to a central depot and then onward distribution direct to sites or via regional hubs? Are comparators needed, and what are the requirements in terms of blinding? Does the central depot handling clinical packaging also have access to preferred suppliers to, one, get a good deal on comparators, and then, two, manage those supplies effectively? It is worth noting that some comparators can be very expensive, so supplies have to be managed very well to minimize waste. Ultimately, when choosing a central depot to perform packaging and labeling activities and onward distribution to clinical sites and/or regional hubs, we need a forward-thinking approach to reach the ultimate goals of minimizing costs, time, waste, but in parallel, maximizing flexibility. Remember, good decisions made in the early stages can benefit you enormously as you scale up to meet the demand of later trial phases. Let's look more intently at Europe now. Now, we naturally tend to think of mainland Europe, but it's important to remember non-E.U countries within that same geographic region, for example, the U.K.. In terms of clinical supply solutions, there are huge opportunities both within the E.U. and non-E.U. countries. Now, between the E.U. and U.K., there are some specifics that we do need to consider. One is the flexibility to meet E.U. versus U.K. clinical demand. We need to think about the QP release strategy. We also need to think about Importer of Record responsibilities and the number of shipments which might incur IOR costs between E.U. and non-E.U. countries. One key consideration for the U.K. is the Customs Warehouse Authorisation. In brief, if you have a central depot in the U.K. who has been authorized to operate as a customs warehouse, then you can import goods into the U.K. and suspend import tax and duties. If the U.K. central depot performs packaging and labeling and then subsequently exports all goods, then you do not have to pay import tax, and therefore you do not have to go through any process of trying to reclaim it. You only pay import tax on supplies that will ultimately be used in the U.K.. So, how do we start to tailor our approach to decide between E.U. and U.K.? Well, let's first of all draw up a picture of the key contributors to a clinical trial. We have the drug product manufacture site. Well, where is that located? Let's also maintain visibility of where the stability test site is and any other analytical test sites, as there will likely be a requirement for the central depot to ship samples to those facilities to support ongoing stability analysis and other analytical testing, for example, ID testing to support QP release activity. Let's assume that bulk shipment of the manufactured drug product is shipped to a central depot in Europe or U.K.. That central depot provides full-service packaging and labeling and distribution to clinical sites and onward shipment to regional hubs. Ideally, the central depot would also have experience of comparator sourcing and in-house capability to provide blinding solutions if required. The number of regional hubs required depends on exactly where the clinical trial is running. In short, consider where it is more conducive to set up a regional hub rather than face the challenges of shipping directly from the central depot to clinical sites in that country. For example, some countries have lengthy import processes, so it makes sense to have a local depot in that country rather than trying to ship direct to clinical sites from a central depot located somewhere else. That is particularly important when considering the required shipping conditions of the clinical trial supplies. You do not want site shipments to be at risk of running beyond the validated time of the shipper box. An alternative would be to use a premium courier, of course, but then your budget will be significantly impacted if you use a premium courier for all site shipments. It is worth noting that regional hubs may also be required to perform packaging and labeling activities, for example, expiry extension labeling and/or comparator sourcing if local supplies are required. Ultimately, we have the clinical site and the end user, the patient. A well-thought-out supply chain should always support having supplies reach the intended user in good time and in good condition without temperature excursions. When coordinating the clinical supply chain, the traditional approach is to have multiple vendors: one for drug development and manufacture, and another for clinical supply services. Another option is to consider vendors that offer an integrated service offering. Just to be clear, either approach works. But when starting out with clinical trial planning, one should look at the pros and cons of each option. Multiple vendors may present favorable budget options, as you can, in essence, shop around a lot more. But you should consider the resource required to manage multiple vendors, ensuring ease of communication and flow of information. Depending on that level of management, the exchange of information between different vendors does sometimes cause a lag between manufacturing and central depot activities, so your overall study timelines may be impacted. In contrast, if you choose an integrated service offering, your central depot essentially has direct access to the manufacturing facility, and an integrated approach between the two different services can more readily support supply versus demand discussions to then work out a better overall plan to improve timelines and maintain good visibility and good control of future projections. Let's look more closely now at the U.K.. Let's assume that the central depot is located in the U.K.. From previous sites, you will recall that the central depot takes lead responsibility for full-service packaging, labeling, and distribution. So, how might that then work if you have clinical sites in E.U. countries? For the benefit of this presentation, we have called the process Extended Pass-Through. So, at the central depot in the U.K., your clinical supplies are packaged, labelled, and an interim QP release is performed to support the shipment of supplies from the U.K. to the E.U., but that interim QP release also supports the final E.U. QP release once the stock arrives into the E.U.. A shipment order comes in. Now, that might be a manual shipment request or an IRT shipment order. The order is processed, packed, and distributed from the UK depot. Supplies are transported in a temperature-controlled vehicle from the U.K. to the E.U., going through E.U. customs clearance, complying with trade importation regulations into the E.U.. Supplies are delivered via the E.U. depot, where the final E.U. QP release trial is completed prior to onward transportation to the clinical site. Just to be clear here, full depot setup is not done in the E.U.. The E.U. depot only supports the extended pass-through shipment. It perhaps sounds a little complicated compared to simply setting up a depot in the E.U.. However, it might be that the savings you make through packaging in the U.K. make it worthwhile, at least exploring the extended pass-through approach. The idea is that you do not duplicate QP release activity, but instead coordinate between the U.K. and E.U. QPs, have a QP/QP agreement in place, and in essence, split out the release activities. From an IOR perspective, then, the E.U. depot would or could act in that capacity for all shipments originating from the U.K.. The next few slides are designed to help us identify when the extended pass-through approach might work best. So, let's assume the central depot is in the U.K. In this case, we have clinical sites in the U.K., and we also have clinical sites in the E.U. But let's consider then the expected number of site shipments in the E.U. If the volume of shipments is expected to be high, then it makes sense to do a full depot setup in the E.U. If the volume of shipments is expected to be low, however, then shipments could be handled via the extended pass-through approach. In this next example, the central depot is again in the U.K., but this time we do not have clinical sites in the U.K. Again, depending on the volume of shipments going to E.U. clinical sites, one might consider either setting up a depot in the E.U. if site shipment volumes are expected to be high, or taking the extended pass-through approach if shipment volumes are expected to be lower. You might think immediately, "Well, why have the central depot in the U.K. at all? Let's just go with the E.U. depot." However, think back to the U.K. Customs Warehouse Authorisation. Packaging and labelling costs may be significantly lower in the U.K. compared to mainland Europe, so if you do not have to pay import tax and duties in the U.K., and packaging costs are lower in the U.K., it may still be of financial benefit to consider the central depot location in the U.K.. Let's consider now the central depot being located in the E.U.. Regardless of the number of clinical sites in the E.U., the supplies are already there in Europe, so leave them there. They are already where they need to be. But if you also have clinical sites in the U.K., then you would need to consider setting up a U.K. depot to handle the U.K. site shipments. Again, let's consider the central depot again in the E.U., but this time there are no clinical sites in the E.U.. If there are clinical sites in the U.K., then you would, yes, consider a U.K. depot, and depending on whatever other countries are participating in the trial, maybe also set up other regional depots across the world. Like before, you might think immediately, "Why have a central depot in the E.U. at all?" But let's think back to some of the points we've already covered. It's important to engage with the right central depot to meet the needs of your trial overall. For example, if your drug product has particular characteristics that only certain parties can handle, if comparator sourcing is required and good access to global suppliers is important, if your focus is on particular central depot KPIs, then a central depot in Europe or the U.K. may still present benefits. Finally, let's consider the central depot somewhere else, for example, in the U.S. or Asia Pacific. Depending on the number of clinical trials in the U.K. versus the E.U., you might consider options to set up a depot in the E.U., in the U.K., alternatively just the U.K. with extended pass-through shipments to E.U. clinical sites. There's no correct answer here. The purpose of these slides is to encourage the forward-thinking approach that we spoke about earlier. Of course, at the start of a trial, we do not always know the final list of countries that will participate. If, for example, patient enrollment is slow for whatever reason, then clinical teams may consider other countries coming on board later on. That said, the decision on central depot location should be supported by discussions around the general experience of that depot to support global logistics, such that any adaptations through the course of a trial are relatively painless. I think we can all agree there is a lot to think about when coordinating clinical trials, and specifically the supply planning through a central depot vendor. I have heard on other presentations the analogy: "It's a bit like following a recipe." Well, yes and no. It's more like you have to develop the recipe in the first place, then you follow the recipe, but then you also need to make adjustments to the recipe if required. So, where would you begin? Scenario planning is key, and what you see on this slide is a high-level overview to support getting the building blocks of information together so that we can start to tailor our clinical supply plan. On the right-hand side, a simplified scope of the central depot requirements is detailed. We're, for example, packaging vials into a carton. We're labelling with a multilanguage booklet label. There are 4 bulk batches being manufactured originating in the E.U. QP release is required. Drug product is refrigerated. We know the study duration. We have a projected number of shipments per clinical site, and we know that the central depot also needs to support returns and destruction from those clinical sites. We know our countries, so let's start to then think about how we might handle this in terms of clinical supply planning. Let's assume our central depot is in the U.K. Based on the countries participating in the study, we would have our central depot in the U.K., but then also regional hubs, one in the U.S. to support distribution to clinical sites in the U.S. and Canada, but also a depot in Asia Pacific. The example here is in Singapore, and that would be to support distribution to clinical sites in Australia. A question would be: do we also need to set up a depot in the E.U.? Following the criteria we reviewed earlier, we do have the means to project overall site shipments to E.U. sites, and that helps to determine which approach we take. Do we set up a depot in the E.U., or would we consider the extended pass-through from the U.K. depot? It might work very well in this particular example. That said, would we need to support the extended pass-through approach? Well, if we're going down that road, you can see we can then start to build the picture around importer of record and around the QP release strategy. We look at the number of batches being manufactured, for example, so we can project, "Okay, we have 4 bulk batches coming into the U.K.." You have to think about your drug product. There's an example there. Well, if it's a biologic, from a QP release perspective, ideally you should be having those discussions very early on to align the right QP to the release activity on this particular trial. Biologics, for example, are a little bit quirky, so experienced QP resource is advisable. You then look at how many packaging events there will be, how many finished kits/lots that we will produce, and therefore what that kind of outlook looks like in terms of release activity. And then, as shipments go from the U.K. to the E.U., the number of QP release activities per shipment into the E.U., and you can start to build that bigger picture to enable good decisions to be made. Through the presentation, I have mentioned the drug product here and there, but I do want to further emphasize that the characteristics of the drug product are key to working out the best supply strategy. If we cannot maintain the integrity of patient supplies through the logistical plan we have chosen, then we have a big problem. So, let's look at the drug product in a little more depth. At a very high level, we might simply look at where the drug product is being manufactured, and a central depot may be chosen based purely on the ease of transferring bulk supply from the manufacturer, looking at export from the country of manufacture and import into wherever the central depot is located. But let's not forget about the drug product itself. We need to consider the availability of stability data and whether that supports any time-out of environment. If it does, then what are those tolerances? If the drug product is refrigerated or frozen, and/or if there is no time-out of environment allowed, then the choice of central and regional depots should support proximity, not necessarily to the manufacturer site, as premium couriers are typically used on those bulk shipments, but certainly proximity to clinical sites. Does your product have any special handling conditions of note? There should be discussions around potent and controlled drugs, for example, to ensure that all relevant parties can handle the drug product in the first instance, but that there are then considerations around any specific constraints around shipping volumes, just to make sure there is coverage there. Studies with short screening times or where treatments are for acute indications and administrations, then more in-depth discussions around logistics to clinical sites are recommended. Is direct to patients required? It might be that not every depot supports that service, so again, in-depth discussion is needed. We come back to comparators again. Does your central depot of choice have the means to source and manage those supplies effectively? Some drug products and comparators are very expensive, so it's important to select a central depot that can handle supplies well to minimize waste. We have previously looked at trial complexity, but we only reviewed trial design at a high level. A trial might, in theory, be very simply designed to begin with, but depending on clinical results, could be adapted by protocol amendments to include additional cohorts of patients on differing treatment plans. So, it is important to select a central depot that can supply a wide variety of services, not just the simple solution requested at the outset. If a clinical trial adapts to include other countries at a later stage, does the central depot have the network capability and experience of countries other than the ones you know are starting out on the trial? There are other factors that also need to be considered. Blinding is a very important feature of clinical trials, and it is important to understand the capability of the central depot to manage this. Blinding of patient kits can be very straightforward, but sometimes, depending on the presentation of the drug, more intricate blinding solutions are required. An example would be a prefilled syringe that has to be blinded against a comparator. It might be that a bespoke masking unit has to be engineered to enable dispensation of the IP or comparator while maintaining the blind of the treatment overall. Can the central depot deliver that? One other factor to think about when choosing a central depot is the study team itself. Running a clinical trial is challenging enough without issues around communication and information flow, so do think about the multiple vendors versus integrated service offerings and ask yourself what is truly manageable for you. When engaging with vendors, ask them about real-time access to inventory and shipping information, as many will support that kind of service. If you are working with multiple vendors, do communicate key milestones to all key parties and ensure there is a projection forecast that is carefully monitored and reviewed periodically with that wider team. Maybe consider bringing in an external resource to support your clinical supply management decisions. Remember, what you can do now to future-proof your decisions may benefit you quite significantly in the long term. Consider language differences: what's going to work best for you to ensure that all key stakeholders understand exactly what needs to happen and to ensure there is no confusion or misunderstanding? Consider time differences: if you have key stakeholders on opposite sides of the world, a central depot in the European region might be of benefit to provide same-day overlap with most parties to drive actions through without having to wait for next-day responses. To be honest, I'm being very candid here, I did think about putting together a summary slide, but the nature of clinical supply planning is such that one size does not fit all, and when deciding on your central depot, you should consider capabilities beyond just those that you need right now. Hopefully, what I have presented today does give you some insight into strategically planning your clinical supplies, considering E.U. and non-E.U. countries like the U.K., but also prompts you to think about other key considerations to future-proof your choices so that you can make the right decisions for the right reasons at the right time. Thank you for listening, and I hope you found this presentation useful. I will hand back to Jeanne to see if we have any questions to address. Thank you, Dr. Quinn. We do, in fact, have some really great questions populating in from the audience. I'm really excited to get to those terrific insights today. I absolutely loved your recipe analogy, and in general, just what you're saying about the importance of individualized decisions here. So, before we do kick into our Q&A session, I just wanted to remind our audience how you can submit a question or more than one question to Dr. Quinn. You can submit any questions you have by typing them in the Q&A box that can be found directly below your video player. Dr. Quinn, first question: maybe you can provide an example of where a key decision during Phase I has benefited later phases, and maybe you can highlight some of those benefits. Great question, and there will be multiple examples that many of the audience will have some themselves, and we'd be interested to hear what some of those are, so please do feel free to give feedback as well as questions as well. I think one example: so let's say you have a tablet formulation. Data indicates the drug product is pretty stable. You're planning a Phase I clinical trial. Well, think ahead towards what the Phase II or III might look like, and you might, for example, consider patients attending clinic on a monthly basis. Now, patient schedules are not always routine. Some flex does need to be allowed to support patients struggling to attend visits at clinics, maybe working around holidays, and IRTs will generally allow a visit schedule with a tolerance of X number of days. So, why not think now, ahead of your Phase I, about setting down stability of a 40-count bottle? You will then go into Phases II and III with a much bigger stability data set. You'll save significant costs by being able to plan larger manufacture volumes, reducing the number of packaging and labeling events, and potentially also reducing the number of depot shipments. Now, that's just one example, but I guess going back to the presentation as a whole, think about those building blocks of information and do go through scenario plans. You know, however your brain works, throw information together, whether it's on a slide, on a spreadsheet, start to just strategically think. It's imperative. There are huge benefits. If you make the key right decisions early on, you can reap big rewards in terms of cost, time, and effort. So hopefully that's addressed the question and given people food for thought. Great, thank you again. Great points. So, Dr. Quinn, more on some benefits here. What is the benefit of sourcing comparator supplies from the E.U. and U.K.? Another great question. So, so comparators, we know they can be very, very expensive, and we do often see the price of comparators varying quite significantly between different regions, different markets. It's not uncommon for comparators to be anything up to, let's say, a third cheaper from the European market compared to the U.S. market. That's just one example. European supplies, it's important to note this, European supplies often come with a CofA or a pedigree document or a CofC at least, so they are suitable for release to most countries outside of Europe. Now, you do need to understand requirements for certain countries, though. The U.S. FDA, for example, will only approve the use of European comparators if there is no possibility of sourcing the same supplies in the U.S. But that in itself brings us to another interesting point. As some of us will have heard on the global news, certain drugs are in short supply in some countries right now. So, for a drug that is typically available but currently in short supply, that may be sufficient rationale to obtain FDA approval, for example. So it is a fluid situation, but it's definitely worth looking at. There are huge cost benefits, to source comparators from European markets. Like everything else, you need to shop around, but definitely worth looking at. Great, thank you. I'd like to move on now and talk a little bit more about roles and responsibilities. So, our first question on the topic of responsibilities relates to the importer of record. Can you clarify the IOR responsibilities in the E.U. and U.K.? Like, for instance, who is actually responsible, and when are those fees applicable? Yeah, sure. So, in short, whoever owns the supplies is generally responsible as importer of record and coordinates the payment of import tax and duties upon import of supplies into a country. Import tax is applicable generally at the point of entry into a country. All countries have varying rates of import tax, and it is payable based on the value of the goods imported. Now, where you do not have a legal entity in that country or region, the IOR responsibility may be delegated, for example, to the central or regional depot in that country. There's usually a nominal admin fee for a depot to act as an IOR, and whilst they will coordinate the payment of import tax to the local authorities, that will be billed back to the sponsor. Now, in the U.K., there is the Customs Warehouse Authorisation, which allows the suspension of import tax being applied to goods delivered into a U.K. depot with that authorisation. Then, what happens to the supplies in the U.K. ultimately will drive exactly how much import tax is billed. In short, tax will only apply to goods that are used in the U.K. So, that's quite key, and there could be cost savings there, for example, if you have a central depot in the U.K. Yeah, absolutely. Really good to know about that. So, can you possibly clarify the QP release strategy then if you're sending kits from the U.K. to the E.U.? So, in short, it's very important to remember that there is no expectation to ever duplicate QP release activity. If, for example, a drug product is manufactured, then packaged and labeled in the U.K., the U.K. QP would perform an interim release for supplies going to the E.U. and a full QP release for all other non-E.U. countries. The interim release for E.U. supplies would cover, let's say, approximately 80% of the full QP release activity, such that when supplies arrive into the EU, the E.U. QP completes the remaining 20% of the overall release activity. So, we're not never duplicating; there will be no duplication of effort and, therefore, costs associated with that effort. It's about having early discussions between the different QPs on your supply chain and making sure that roles and responsibilities are well understood so that there is no duplication and there's a slick process. Everybody knows which bits of the release activity they are doing, and ultimately you have a very speedy and, you know, not labor-intensive. There's no duplication there at all, so it should be well thought out in advance such that everybody knows what they're doing so that you don't then have any trouble. So, we've discussed benefits, right? We've discussed the impact on cost. We've also discussed roles and responsibilities. Help us wrap up today's discussion. Maybe you can talk a little about the timing of shipments from the U.K. to the E.U., comparing site shipments from the E.U. depot. So, so ultimately, when considering the timings for any site shipments, you should have detailed discussions with the central depot to ensure transit times meet the needs of the trial in terms of drug product stability, shipping materials used, urgency of delivery to meet patient needs, etc. With a well-mapped out process and a good understanding of the turnaround time required, extended pass-through shipment from the U.K. versus a site shipment from an E.U. depot should be fairly comparable, with perhaps just one extra day to account for the E.U. QP release activity per shipment. So yeah, we're not overcomplicating this process. Like I mentioned on the last question, with good discussions in advance, everybody knows what they're doing, it's then a very slick operation to get supplies from the U.K. to the E.U. clinical sites. Great, thank you so much, Dr. Quinn. You know, you did a really great job providing over these insights today, and reinforcing the value of proper preparedness, right? So, unfortunately, we are out of time with today's discussion, but I want to thank you so much for joining us. I also want, of course, to thank our audience. Some really great questions did come in. I know there were some additional questions that populated that Dr. Quinn did not have time to respond to live today, but I want to let you know that she will also be responding offline. Most importantly, I'd like to thank Catalent for making today's presentation possible. As we do conclude with today's presentation, we'd also like to ask our audience if they would kindly participate in a brief survey. The survey will appear on your screen just after today's presentation has concluded. We greatly appreciate your insights. You'll also receive an email alerting you when Dr. Quinn's presentation is available for replay. We invite you to forward this announcement to any colleagues who may have missed today's live event. Again, thank you to everybody so much for joining, and we'll see you next time. Goodbye.