The Fortrea Podcast
The Fortrea Podcast
Radiopharmaceuticals Trials: An Operational Playbook | Ep 3 | Manufacturing & Distribution Constraints: When Precision Meets Pressure
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This episode of Radiopharmaceutical Trials: An Operational Playbook takes a closer look at the critical role of manufacturing, quality release, and cross-border distribution in radiopharmaceutical trials—where every minute counts. It explores the operational complexity of producing and delivering treatments under extreme time constraints and strict regulatory controls.
The conversation highlights how precision at every step directly impacts whether patients can receive their dose on time.
Host: Hector Herrero, Senior Director on Global Project Management at Fortrea
Participant: Graham McCarthy, MIAS Pharma
Hello everyone, welcome back to the podcast. I'm Hector Arrero, Senior Director of Project Management at Fortria, and today we are continuing our journey through the operational reality behind radiopharmaceutical clinical trials. In our last episode, we talk about why logistics is such a critical text back for radiopharmaceutical trials, timing, coordination, and patient safety. Today we are going one step up and we will be talking about manufacturing, release, and distribution. Because before a dose ever reach a patient, it has to be produced under stream time constraints, quality release, transported often across, or better said always across borders, and deliver in a window that leaves very little room for error. To unpack this, I'm joined by Graham McCarthy from Mia's Pharma. Graham, welcome again. Great to have you here.
SPEAKER_01Thank you, Hector. It's lovely to be back.
SPEAKER_00So let's start talking about uh manufacturing and distribution, which uh is also key and very, very relevant for these radiopharmaceutical trials. So, what makes manufacturing radiopharmaceuticals so time sensitive?
SPEAKER_01It's really that's the half-life of the material. The product simply can't be stockpiled. Once it's manufactured, it generally has to be within the patient within, say, up to 96 hours. That means that it has to be manufactured, transported, quality elements have to be done, and it has to be administered to the patient within this time frame.
SPEAKER_00So, how do narrow production windows affect patient scheduling at the site? And also very important, when things go wrong, it's often not just one point of failure, it's probably coordination. Where do you most commonly see breakdowns between manufacturing and clinical teams?
SPEAKER_01Those are two very different questions. So around the communication side, a lot of the forecasts are driven by patient recruitment. So basically, the clinical the sponsored clinical site, QP, the manufacturer site would work more or less hand-in-hand on this piece. So basically, there's no batch of is going to be manufactured unless the clinical team places the order. The only time that anything will really happen around cancellation of orders is if the patient is maybe too sick to get the treatment or can't get on site in time. Around scheduling is the challenge that we find is most manufacturers operate within a set manufacturing window, be it midweek or over weekend. So that in itself it creates capacity issues. Clinics also have certain capacities on how many doses can be administered as it is confined specific days, and sometimes it has to be used in conjunction with PET scanners. Finally, from a logistics point of view, it's the axis of flights and even from a QP point of view. An average batch can take six hours while the product is in the air. So if it's going to be multiple batches in a given day, we need to have multiple people ready on standby to release. Again, all those tie back into patient scheduling because it defines capacity of what can be done.
SPEAKER_00At the end of the day, all these processes are going to impact patients. Patients at the site waiting to be treated. And all this manufacturing is also to be taken into consideration when we think about which is the capacity of the sites not only to handle the patients, but also to administer certain levels of radiation. This was also covered previously, but it is something that we always need to keep in mind. Before we add all these international achievements, we already have a just-in-time system with almost no Slack. So let's add here the next lawyer, which will be the cross-border transport. So are there any common challenges that the sponsors or manufacturers may encounter when import and transport that they may usually overlook?
SPEAKER_01Yes, I suppose it's the short answer. So, look, we all know transporting radioactive materials involves license carriers, radiation appliance, and it does, as you said, come to tight timeline. One of the biggest things we encounter is sponsors not realizing that there's a QP element for Europe that's acquired. So basically there's no product that can go into a patient unless it's QP release. Um, etc. So the study can actually be taking place. The second challenge is that, especially um with sponsors coming from third countries, is if if a sponsor is looking to carry out, let's say, a study in let's say Germany, in their mind the product's going to go straight from the US or Canada into Germany. The reality is a couple of years ago, Annex 21 came into place in Europe, which means that there has to be a designated location or set-down point with which the radio pharmaceutical material has to touch before it can move on. In our own studies, we leveraged a site in Belgium. So basically the product has to, irrespective of where the final destination is, it has to touch down in Belgium, and then that time to factor in to get to the other country has to be has to be organized.
SPEAKER_00Maybe just uh one more question on this topic. So because even within the same region, timelines can look totally different. So, how do country-specific regulations affect timelines?
SPEAKER_01Having the set side of importation actually makes it easier because previously you'd have to notify all the various countries. If it's all going through one central point, it's only one country you have to deal with. Now you do need, from a logistics point of view, relevant licenses and authorizations to allow the product to pass through various countries. Um, but uh in in in essence, at the time of the study, all the potential blockers should have been worked out through the MUC shouldn't. So these are the variations: IOR, QP onboarding, ASNs if it's going to France. So basically, um it's just it's back to operational.
SPEAKER_00So so far we have uh talked about making the dose, okay, and then moving the dose, right, to the side. But there is also a crucial gate in between, which is the release uh in certain regions, of course. So let's talk about this qualified person release because in some regions, as mentioned, it is a make or break dependency. So why is a qualified person release such a critical dependency in some regions?
SPEAKER_01Well, it's it's a legislative requirement. So the reality is that no radio flower product, be it in the EU or UK, can be imported or administered to a patient. Well, first the study being linked to an MIA, and secondly, without a QP actually signing off the product and dose. So within Europe, a QP is a step that has to take place, it doesn't exist outside of Europe. It's the final quality check where they take responsibility for the batch to make sure it's compliant with GMP so it's it's as safe as possible to go into the patient.
SPEAKER_00Good. So how tightly does QP release need to align with dosing a schedule? Or in other words, how close to administration are we talking? And one one key thing here as well: are there differences if we are talking about a radionucleite only, or if we are talking about a radionucleide plus an antibody?
SPEAKER_01If there's an antibody, typically the mab will be released ahead of time. So let's say that could take 20 to 30 hours to review that batch. In terms of in parallel, when the manufacturing step happens, the QP is reviewing those batch documents, the manufacturing records, testing results while the plane is in the air. So typically they have we we usually allow up to six hours. So essentially that's from going through the records, resolving any um quality events, and getting the final temperature records so they can actually make a call on if the if the the dose can go to the patient.
SPEAKER_00And what typically causes uh delays at this estate?
SPEAKER_01From our side is documentation being not available. So delays in the actual manufacturer side uploading batch and testing records. From time to time, maybe a delay of one or two hours of customs, or delay of when the courier um gets a site of them issuing us back the temperature records at the clinical site. So we can't find we can't do the conditional release until we have temperature records.
SPEAKER_00Oh Graham, this is really, really, really helpful. If if I summarize uh radiopharmaceutical trials run on a just-in-time model, okay? Manufacturing in time, transporting in time, crossing boarding on time, release time all have to align to the patient minute by minute. When you add cross-border transport and QP release dependencies, the system really becomes very sensitive to small delays, as we have been discussing. And especially when we are also talking about weekends, holidays, and custom cutoff times. So before we close, one practical question for teams listening. One habit or checkpoint you would recommend to reduce avoidable last-minute surprises.
SPEAKER_01Take time to do your mock shipments for your various countries and sites. Involve a company like MayaS early in the process to make sure you're not going to get blocked or anything in terms of regulation compliance. Work hand in hand with your QP. So the reality is as as studies scale up, manufacture site does increase. On the back end, just remember that person has six hours in most cases to do all the reviews and to release the back. So, for example, if there's five batches going in one single day, we need to resource accordingly. So it's really important that we have forecasts and a vision of how studies are going to wrap up so we can scale appropriately.
SPEAKER_00Uh Graham McCarthy from Mia's Pharma, thank you uh very, very much for joining us and for sharing all your experience and uh insights. And thanks to all of you for listening. If you found this episode uh useful, subscribe to Fortria Podcast and please share it with your colleagues working in clinical operations, manufacturing, and logistics. Anyone navigating the reality of time critical supply chains. Take care.