Considering the complexities and intricacies involved in personalized medicine research and development, it stands to reason that the logistical issues associated with the field also are incredibly complex. Nina Vas (vice president of clinical distribution for the cell/gene supply chain for Marken) spoke with Outsourcing-Pharma about the formidable challenges in getting such sensitive items from place to place, and how to tackle the obstacles intelligently and effectively.
OSP: Personalized medicine is a rapidly growing and evolving field. What kinds of conversations has Marken had with clients in the pharma and clinical research fields?
NV: It is about having the appropriate supply chain that’s not necessarily a copy and paste. In particular, we take the time to conduct risk analysis, feasibility and assessment and provide a bespoke service.
When we talk about cell and gene, it is exactly what you said in the title. A personalized approach in terms of how we work together, collaborate and execute through setups.
OSP: What unique needs and challenges does the personalized medicine realm have to tangle with that other clinical supply chain clients might not be concerned with?
NV: It comes down to the complexity of the setup. Understanding the individual requirements, and that it’s not a single shipment. What we typically do is look at the series of legs.
The individual parts of the journey that make up the entire cell and gene shipment for an individual patient. And within that is understanding the complexity of the chain of custody, so that you have those clear handoffs, the risk mitigation in terms of backup, and redundancy, for each individual leg — you have not just a backup lane, but perhaps a tertiary lane, and even up to five or six alternatives. What you’re not relying on is a standard A to B transfer of medication for example, which you would be able to do quite readily with a solid oral dose ambient (15 to 25 °C) shipment.
OSP: I imagine refrigerated temperature-sensitive items are a whole other ball of wax.
NV: Absolutely; the temperature and condition of the product are key. What we’re typically seeing is leveraging liquid nitrogen and dry ice shipments. The complexity of the shipment in terms of the product packaging.
From a shipment packaging perspective, this is more involved and also qualified by the individual customer for that particular product and individual supply chain. It could be an off-the-shelf solution, but it is qualified for that individual product by both quality teams to ensure that you have a solution that is as robust as it possibly can be, knowing the value of the personalized shipment that you’re making.
OSP: Does Marken partner with any specialized packaging companies — containers, cold-pack insert, or things like that?
NV: We have our own fleet and packaging materials, right through from controlled/ambient until refrigerated/frozen. including dry ice as well as liquid nitrogen; our own fleet of dewars positioned globally. As an organization, we work with a number of vendors in terms of the different types of materials (packaging and temperature monitors, GPS trackers).
Often a customer has a shipper approved for their cell and gene product, which dovetails perfectly with Marken’s current fleet which we have strategically positioned all over the world at all our logistics branches in all four regions, LATAM, NORAM, EMEA, and APAC.
However, at times a customer may have another qualified for their product that they’ve developed early through clinical trial phases. They perhaps are engaging Marken at a later stage once that supply chain in terms of packaging has been long established and approved by their quality team. They don’t necessarily want to change midstream strategy, mid-clinical trial, or through commercial.
Marken is able to strategically partner and understand that we have the ability to be flexible. Whether we’re storing and providing logistics support through the Marken network, we’re also flexible enough and agile enough that we can leverage pickup of customer-approved shipping solutions from an alternative supplier and rapidly implement this within the Marken packaging supply chain including positioning in different regions.
OSP: Time constraints are usually a top priority — could you please share some detail on how precision-medicine-involved logistics are especially demanding in terms of turnaround, and how companies can work to ensure they can meet these needs?
NV: The key is the upfront planning, that risk mitigation which we touched upon briefly earlier. Lane mapping and management. If you are moving product from the U.S. manufacturing facility to perhaps a patient in Australia, you have to understand the individual flight schedules, the total transit time, the window that you have, and what are the constraints in terms of handover points from a chain of custody perspective.
We can have collection windows as short as 15 or 30 minutes for handoffs within the supply chain, we can have specified timeframes. From a manufacturing perspective, working with the customer to understand manufacturing schedules is key. Upfront preparation, the execution of mock shipments in advance allows you to navigate that complex landscape in terms of understanding the demands of those shipments and lanes.
Questions to consider, what happens when your shipment is off-loaded on an international flight, which can occur so even though they’re declared accordingly, with clinical trial or commercial, medicinal product, as part of the bill of lading for the airline, you still have that unfortunate situation.
At times if it’s a commercial airline, your cargo can be off-loaded. What do you do? You may have to extract the shipment from the airline, if it’s just a particular issue with that flight on that day. Activate an alternative route, if it’s an international shipment to perhaps your second airline.
If it is not an international shipment, but a domestic flight, you may have the opportunity to extract and move to a road as a backup solution, with a direct drive. That’s a complexity and, again, perhaps with a non-cell and gene shipment in a clinical trial, you would have the opportunity that 24-hour delay may not be critical, but in cell and gene, a 24-hour delay can mean the loss of a product.
OSP: Navigating the complex regulatory landscape can become even more intricate when precision medications are the cargo in question. What are some of the important questions clinical trial teams and sponsors should ask?
NV: Preparation, and more preparation. Understanding the markets or shipping destinations to working with your customer in order to be able to execute mock runs. Mock shipment execution is not just the physical test shipment execution, but all the paperwork associated with the shipment.
For example, if you require temporary or even permanent storage, you work with your facility, your storage depot to execute a mock reception into their inventory system, test the inventory process, walk through those individual steps. In order that you have copies of all of your documentation as part of that mock run. In addition, you test the full release process.
Understanding that you have the appropriate certificates of analysis available, even for the mock shipment, so that you are walking through from beginning to end. You’re double- and triple-checking, not just the physical and operational aspects, but the documentation running in parallel, and within that very same process.
OSP: For international trials, or studies with sites in more than one country, how do you recommend clients keep all the complex regulations, import/export requirements, and other details straight?
NV: What we don’t do is provide regulatory support on the product itself. However, at Marken, we have an extensive database when it comes to import and export support and requirements. We benefit from having experience in supporting multiple customers.
From a pure crossing borders respect, we can give key customers access to our import/export database. We do support global trials for multiple sponsors. And what we see in cell and gene in particular which may be slightly different from a traditional clinical trial or non-personalized trial, is that the launch of new countries is often completed sequentially rather than in parallel. This gives the sponsor and Marken together the opportunity to have a very measured, phased approach to going live or launching in multiple countries.
We do not often see that six or seven countries launch, all on the same week, or within the same month; we see very much that staggered, measured, calculated approach, which again, comes back to that risk mitigation planning which we discussed earlier.
OSP: What else would you like to add that we didn’t touch upon above?
NV: Additional items which are key for the distribution of cell and gene and personalized medication as it is increasing rapidly are storage, replenishment, tracking, and integration with orchestration platforms; having the ability to think about not just your regional storage, but also your decentralized storage.
- Do you have LN2 and dry ice filling stations along your supply chain in the event of an emergency as part of that risk mitigation planning, that you map out and plot your backup secondary and tertiary lanes?
- Do you have the ability, worst-case scenario, that you can rapidly move your product into temporary storage if required in the event of a lane not developing the way that you anticipated, or you’ve just had a risk in the supply chain?
- Where are my backup locations? Am I able to track my product in real-time, leverage GPS tracking?
- Do I have a team proactively monitoring my shipments and being able to anticipate the next actions and executive alternative actions within approved parameters?
- Have I allowed adequate time during setup to integrate with my orchestration platform?
- Finally, is my selected supply chain partner able to help me not just reduce the risk throughout my personalized supply chain, but able to anticipate and mitigate risks during live operations and provide support?