Precision Therapies: Reinventing Pharma Logistics

In this episode of the Pharma.Aero Insights podcast, we explore the unique and evolving logistics landscape for precision therapies, focusing on cell, gene, and radioligand treatments.

Join Frank Van Gelder and his guests
Jade Verrept, POM Antwerp (Development Agency of the Antwerp Province) - Cluster Manager of the University of Antwerp Science Park, Point of Contact for the Incubator Darwin, and Co-Founder of at.las ATMP
Mariyam Peñate, Global Account Manager at Expeditors
An D’Hondt, Senior External Manager at PwC Belgium and Project Expert for Pharma.Aero's Precision Therapy Logistics Project

Tune in to learn how these life-saving therapies, with their intricate and highly sensitive supply chains, are pushing the boundaries of traditional pharmaceutical logistics. 

With extreme sensitivity to time and temperature, along with personalized, patient-specific products, precision therapies require an entirely new approach to logistics. Discussions touch on everything from "vein-to-vein" logistics models and make-to-order packaging strategies to the vital role of real-time tracking and specialized handling centres. 

Additional resources:
Pharma.Aero Therapy Logistics Project

Transcript

Precision Therapies: Reinventing the Pharma Logistics

Frank Van Gelder, Pharma.Aero (FVG): Welcome to today's episode of the Pharma.Aero podcast on precision therapy logistics. We're diving into the logistics behind cutting-edge treatments like cell and gene and radioligand therapies, critical life-saving innovations that present unique logistical challenges. But let me first present you our guests today: 
An D’Hondt, Senior External Manager at PwC, Project Expert in the Pharma.Aero Precision Therapy Logistics project,   Mariyam Penate, Global Account Manager at Expeditors, and Jade Verrept, Provost of Antwerp and Cluster Manager of the University of Antwerp Science Park, Point of Contact for the Incubator Darwin and Co-Founder of ATLAS ATMP.
Welcome, ladies. Let's just jump right into this intriguing subject. Jana, being at the University Science Park in Antwerp and involved in ATLAS and the bio-incubator hosting many cell and gene therapy companies, I can imagine that the logistics are not the major concern for those companies. But what if they scale up to commercial?
Jade Verrept (JV): Well, Frank, the researchers and small biotech companies in our community are usually still in the development phase. So their concerns indeed are not of a logistic nature at first but are related to, for instance, funding. Developing an ATMP is very complex, it's very expensive, in part due to the fact that even small-batch manufacturing is to take place in high-level cleanrooms in compliance with GMP, so funding is definitely an issue.
A second concern, I think, is regulation. Luckily, in Flanders, the regulatory authorities are actively seeking out early collaboration with developers to help them with the interpretation of existing guidelines and work towards a clearer framework. This is absolutely necessary.
A third issue, I think, is trying to develop the product in such a way that the manufacturing is actually scalable when you want to go to a commercial phase. An example of why it's actually important to think about logistics early on is because in your process when developing a product, you want it to be stable so that you can ship it. There are examples of ATMPs that were developed in a research phase that had a shelf life of only two hours. That means it's very complicated to build a supply chain around it. And if you don't factor that into your business model, then your product will fail. You will not be able to reach patients. So, with regard to the supply chain, to your question, we do advise early developers, we encourage them to think about the supply chain and allocate the necessary budgets to their logistics, even in the clinical trial phase. And of course, we also try to inform supply chain solution providers of the types of products that are coming their way and the way in which they can prepare for these new products. That's part of the aim of ATLAS ATMP.

FVG: An, you have been heavily involved in this project (n.r. Pharma.Aero Therapy Logistics project). What are the biggest logistical considerations when scaling up these therapies?
An D'Hondt (AD): What we have learned actually is that for these therapies, there is no such thing like a one-fits-all solution. Current logistic solutions for pharmaceuticals will not fit the purpose for these products. Precision therapies will require very different and highly controlled logistic services. Temperature excursions, damage or late arrivals are simply no option anymore. We will need to rethink logistics completely, not improve the current model, but all involved parties need to think out of the box and reinvent themselves. Collaboration will also be a key enabler to make this one work.

FVG: Mariyam, being part of a very healthcare and pharma logistics freight forwarding company, any insights on the logistics world and what we are looking at?
Mariyam Penate: Yes, absolutely. I think one of the key considerations that we should be looking at is to ensure that we are partnering early and partnering thoughtfully and making sure that we are bringing the partner into the supply chain with the developers and the scientists so that they can understand the high stakes and the weight of that social responsibility they have in regards to the product. They will be able to be a part of that proactive planning to ensure that they understand there is zero room for any sort of errors. Because several gene and cell therapy companies are still developing in this area, it helps to bring in an expert who can help not only with the upstream challenges but help foresee what you might be experiencing downstream. And the patient's well-being is going to be dependent upon the logistics partner's ability to execute in a region that we may not be doing business in currently.

FVG: Interesting. The three answers to the first question are literally pointing at a wider and broader collaboration, which is apparently very necessary to make it happen on a wider scale or a bigger scale. Let's move to something else. We face extremely short shelf life and thus very challenging and reactive order methodologies. The new normal is what is called package-to-order, where literally the order is placed upon release of the therapy. Within two to four days, the therapy should arrive at the patient. What can be the specific challenges in this? And Jade, perhaps I would like to start with you.

JV: Maybe it's smart to first point out that we're essentially dealing with two types of products, you could say. You have autologous products, where the starting material of the therapy in fact consists of the patient's own starting material. In that case, you effectively have a closed-loop supply chain centered around the patient. Another term used in this case is vein-to-vein logistics. A second type of products is the allogeneic products, where a donor is used to provide the starting material for the therapy and where it's in fact possible to create an off-the-shelf product. Today, however, for instance, CAR-Ts are mostly autologous products, which is challenging for the supply chain. The main characteristics of this type of supply chain are, one, it's highly personalised, so your chain of identity is crucial. You know, you want to be able to follow your product, to avoid mix-ups. If, for instance, my therapy were to be given to Anne, Anne's immune system would not react well to my therapy. So you really literally cannot have any mix-ups. A second characteristic is indeed the make-to-order or the package-to-order aspect. You cannot create an inventory for this type of product. Simply impossible. A batch is created out of the patient's material. You lose the batch, the process has to start again from the beginning, and the chances are that the patient's material has deteriorated, maybe the patient has died, so there's a chance you do not get a second chance, so you cannot lose the product. A third characteristic I'd like to highlight is low volume, high value. I've understood that pharmacologistics, as probably all logistics, is kind of focused on volume, is volume-driven, and this might be challenging, especially for smaller companies. It's difficult to get the required service from the logistic solution provider, in part also because they don't speak the same language. So I really like what Mariam said earlier in that regard. These products are very time-, temperature sensitive. With regard to time, they're administered to a patient at the hospital in an ICU. So the hospital is waiting with the doctor, with the patient. so any delays have an impact. And temperature, obviously, again for CAR -T, it's minus 196 degrees Celsius. Cells deteriorate super fast, so temperature is also very important. So you have really specific characteristics that adhere to this type of product.

FVG: Very challenging. So if you look then at the logistic service provider, Mariyam, orchestration of the order and the applied logistics, how can we improve fleet times in these cases? Because what I see is that the model that we use today in big pharma is absolutely incompatible with the big wave that might come from these therapies.

MP: Agreed, and I want to reference back to a comment that you've made earlier that we must throw the box out and not try and fit the solution within a box that exists today. Throw the box away and make a brand-new solution. And what we're looking to achieve here absolutely has to be fail-safe. We need to ensure that the service provider understands that we are working towards a clear purpose. Again, if we're bringing them in early, the ideal partner will proactively design a solution that's going to act as a roadmap for success, which is why, as your team is doing the creation of these therapies, your logistics provider, your extension of your supply chain is going to be actively working to create digital twins and models, trying to proactively predict any challenges that you may run into. Your ideal partner will have the knowledge to be able to connect with government officials and connect with customs agencies, they will have those relationships, they'll be able to bring you in as well, so that you're able to get their buy-in and we ensure that we're not running into any delays downstream.

FVG: And An, looking from, I would say, a more holistic or helicopter view, how can we ensure the logistics engine is not sputtering in these crucial treatments?

AD: There are a few key points that all companies involved in these AT &P -related logistics processes like packaging companies, warehousing, transportation companies, and forwarders, should act upon. First of all, be prepared. As a logistics professional, speak with the R &D people. They are the ones that are now running the clinical trials. They have the best insights today into what will be required from a logistics perspective tomorrow for these products. Secondly, and we simply cannot emphasize this enough, we need to ensure that all companies involved in the end-to-end logistics process will be able and collaborative to ensure real-time communication and visibility with regard to these products. A shared platform to keep track of these shipments is, for example, something that would be a big enabler. In my opinion, collaboration and interactivity in the whole ecosystem is key. Companies that will not respect these two key points will either not be allowed to be on board when the ATMP commercial shipment's engine starts, or they will need to leave the car, plane or boat along the way.

FVG: Let us say, ladies, that the ideal world exists, and tomorrow many oncologic treatments can be provided by cell and gene therapies. What would be the ideal logistic scenario following the massive scale-up of this therapy, to be believed 10- to 20-fold in the next decade? Will there be a need for very specialized handling centers at logistical key hubs, in other words, top-wide glove handling of these products, guaranteeing reactivity, resilience, reliability, adaptive logistics, specialized and performant in the operations? And with this I go immediately to you Mariyam, fully Healthcare and Pharma logistics, I would like to start with you on this one.

MP: I agree, absolutely there is a need. While we are working to build that ideal state to ensure that we can execute, we do have to be aware of the complexities of navigating both the modern and archaic side of logistics. And it's an interesting environment that we are in at the moment where one part of the logistics and supply chain world is navigating more towards AI, digital solutions, and modernization. And while we have other parties within the supply chain world that are still leaning a bit towards more of the archaic sides of operations in terms of manual documentation, management, licensing requirements, and other government agency requirements based on the geography that you're operating in. So within the logistics world, you really have to learn to conduct a balance between both worlds. As you're doing that, you just have to make sure that the interdependency upon those multiple parties in the supply chain does not get in the way of the execution. You want to make sure that we're utilizing advanced packaging, real-time monitoring, 24/7 control tower capabilities, and ensure that the partner is equipped to handle the challenges and mitigate those risks on your behalf while we're navigating these two eras of the logistics world.

FVG: An, referring to you, learned from the project that we did already together, and based on the input of your podcast colleagues during this podcast, what is your reaction on this one?

AD: As the logistics services required for these therapies will be as diverse as the individual patients, lead times and corresponding lanes itself, specialised logistics hub and services will be required as well. A wide range of required services and exceptions will be the new normal. Advanced and integrated systems that clearly indicate the logistics requirements and quality as well as location statuses at all time, in hubs or in transit, will be critical. All parties involved in this journey will need to be prepared and highly engaged.

FVG: Ok. And Jade, to close it and pack it, what is your reaction?

JV: Well, I think we have super exciting times ahead of us. Personalised therapies are on the market as we speak, more are coming. Many clinical trials are moving towards or through a phase 3 are getting closer to many patients. At the same time, researchers are working hard to find ways to be able to target solid tumors or resolve issues with regard to immunogenicity in allogeneic therapy. So in the future, this will lead to more therapies, more effective therapies and so forth. And yeah with regard to the impact on logistics. I think different models, different solutions will be necessary depending on the type of product, as Anne said, and on the type of patient population. We currently see companies pursuing a centralised manufacturing strategy with a robust supply chain, as well as decentralised models in which CDMOs are locally used to produce therapies for nearby hospitals. And of course, there's technological innovation as you pointed out earlier. So in times perhaps we will have tiny bedside bioreactors that will manufacture your product at your hospital bed. And I'm really excited as the Science Park and the ATLAS community will be part of the second phase of the PTL project. I think we'll be able to improve the guidelines around ATMP shipping. I look forward to that and I'm also happy with the positive response I've gotten here at the conference where logistic solution providers are really eager to help improve the logistic supply chain for ATMP because I believe that the technologies in fact are there. It's about collaboration, about sharing data, about helping us keep an eye on that entire flow of the therapy from vein to vein and so I'm actually really positive about the future and I'm curious about the things that are about to come.

FVG: Thank you, Jade. Now that you shared the PTL project, let us talk a bit what this project is about. So we are just landing phase one of this precision therapy logistics project in which we have framed really the critical points that we have to look at. And from here we go to another phase, phase two, where we will literally test real shipments over corridors, internationally, to really map the pitfalls, the possible red zones in scaling up logistics when they are coming. And in a third phase we are probably going to look at what should we do around training, what should we do around specialized centers and stuff like that.

So thank you very much for sharing your insightful ideas and knowledge on this project. So a very big thank you to you An, to Mariyam and Jade. And from navigating the challenges of scaling up to ensuring these therapies arrive on time despite extremely short shelf lives, we've covered a lot of ground today. And one word comes back and back and back, that is multidisciplinary or international industry collaboration to map and to do what we have to do. We hope this conversation has provided you with a deeper understanding of the logistics behind life-saving cell, gene and radioligand therapies. 
It's clear that collaboration across stakeholders' innovative technologies like real-time tracking and reducing handoffs will be key to overcoming the challenges we face as we work to deliver these therapies at scale. Even very specialized, well -trained and technologically well-equipped fast access centers might be of value and perhaps we can even go bedside to the patient just to develop therapy at the moment itself. If you enjoyed today's discussion, be sure to subscribe for future episodes where we will continue to explore the evolving landscape of pharma logistics. Until next time, my name is Frank Van Gelder. It was a pleasure to have you with us and thank you for tuning in on our podcast series.