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Agnes Shanley is senior editor of BioPharm International.
Longer packouts are becoming the rule, as logistics service providers and sponsors gain experience planning logistics for clinical trials involving cell and gene therapies.
Biopharmaceuticals are becoming more prominent in the overall pharmaceuticals markets. In 2016, according to projections by analysts at IMS’ Institute for Healthcare Informatics, seven of the 10 top-selling drugs sold in the United States were large molecules (1). By the end of this year, IMS predicts that biologics will account for roughly 20% of the total pharmaceutical market.
As manufacturers move into new markets and launch new clinical research programs, including work in the development of cell, gene, and tissue therapies, ensuring the integrity of the cold chain has become more important, and more challenging, than ever.
Success involves careful partner selection and logistics planning, as well as proactive communication with shippers, freight forwarders, and logistics specialists. It also depends on new temperature-control technologies, a number of which have recently been commercialized. In 2016, UPS bought Marken Technologies, which specializes in clinical trial shipments, to strengthen its capabilities in this area.
In this overview, Ron Swistock, director of global healthcare strategy at UPS, discusses overall biopharm logistics trends, while he, Mike Sweeney, senior director of global service development, and James Klingelhoefer, regional sales director, both with World Courier, share insights into some of the challenges posed by personalized medicine, and innovative biological treatments such as gene and cell therapies.
BioPharm: How are the biopharmaceutical industry’s cold-chain packaging needs changing?
Swistock (UPS): Pharmaceutical companies are under increased pressure to understand carrier ambient environments in order to develop or justify their transportation methods and risk mitigation plans. Pharma companies are also finding a greater need to optimize the product carton and shipping carton, to minimize unused space, and select more precise packaging configurations.
You’ll see more efforts placed on sustainable materials, and demand will grow for carriers to offer more temperature controls within their networks to minimize packout complexities, costs, and requirements. An increased number of pharmaceutical companies are also innovating and collaborating with reputable third-party logistics companies to create better efficiencies for shipping biopharmaceuticals and clinical trial specimens.
BioPharm: What specific changes are you seeing?
Swistock (UPS): There is more interest in reuseable shippers. These may be more expensive up front but they enable a ‘just-in-time’ business model. For the receiving lab, this approach not only offers environmental disposal advantages, but saves floor space because they no longer have to store used shippers.
BioPharm: What improvements are you seeing in packouts?
Swistock (UPS): Temperature-control technology is improving, and packouts can be much longer than they were in the past. Traditionally, the packout standard has been 24 hours up to 48 hours, but now efforts are being made to bring that up to 96 hours.
If shippers can provide this level of protection for a two-day trip, it will help ensure safety in case of transportation and weather delays.
Important capabilities include replenishment of dry ice and ensuring the integrity of shipment. UPS works closely with its business partner, Cryoport, and uses Cryoport’s dewars, and shipments can be initiated from either Cryoport’s or UPS’ websites.
BioPharm: How is serialization affecting packaging equipment design and features?
Swistock (UPS): With the Drug Supply Chain Security Act (DSCSA), healthcare companies are getting in lockstep with establishing an interoperable track-and-trace system based on a unique numerical identifier. Complying with elements of the DSCSA is an ongoing process that must fully take shape sooner rather than later.
From altering highly regulated packaging to implementing a sophisticated system of issuing unique product identifiers, all of this aggressive maneuvering is aimed at better protecting the drug supply, consumers, and patients.
BioPharm: What role are new biological treatments (e.g., cell and gene therapies) playing in the clinical trial logistics business today, and how does planning for trials with these products differ from traditional clinical trial logistics?
Swistock (UPS): These treatments are still a small part of the clinical trials business, but they require a large amount of front-end planning. Over the past few years, we’ve seen that sponsors really want to know how integration can play a greater role. These studies require cryogenic shipping, so the ability to accommodate dewars seamlessly within our network will remain a priority.
Sweeney (World Courier): Cell- and gene-therapy products require extensive logistical planning. In the case of autologous cell therapies, the patient’s cells are the active pharmaceutical ingredient used in the manufacturing of the end therapy. Therefore, the patient becomes a part of the supply chain, and can be directly impacted by delays or problems during the logistics process.
Additionally, particularly with consideration to the severity of the patient’s illness, the logistics timelines are always extremely tight and any deviation can have a far reaching impact on the clinical team, end-therapy manufacturer, and patient.
When contrasted with small-molecule or biologics products, we find that there is much less margin for error with the logistics of cell and gene-therapy products. Scoping suitable time, critical routings, and educating airlines on the special nature of these products are small parts of the overall process.
BioPharm: How should sponsors and contract partners approach collaboration for these projects? What questions are critical to ask logistics and shipping specialists, and what specific functions should each partner assume?
Swistock (UPS): Important questions should revolve around service partners’ experience and safety record with dewars, as well as packouts and how long the shipments will remain viable without taking additional steps.
Klingelhoefer (World Courier): Sponsors and contract partners should collaborate in early planning stages for both early clinical and commercial development. Although early clinical-stage development requires careful planning, when the scale is increased to commercial application, it is absolutely imperative that sophisticated scheduling and tracking practices be put into place.
It is extremely beneficial for logistical plans for both early clinical-stage development and commercial development to be discussed during the planning phases. Questions during these discussions should include the following:
All of these questions should be addressed at the very onset of project planning.
BioPharm: What issues must be taken into account, and how do they affect the choice of temperature-control and other technology, and overall planning?
Klingelhoefer (World Courier): Generally, it will help sponsors to have a basic understanding of the shipping lanes, transit time requirements, and temperature-control parameters in order to be able to anticipate potential issues and allow solutions to be pre-emptively created.
For example, if the end therapy is going to be transported in a liquid nitrogen dry shipper, then sponsors and partners should ask and decide upon the answers to such questions as:
The answers to these questions will help determine responsibilities, and develop a plan of action and set project timeframes.
BioPharm: What are the unique challenges of moving autologous, as compared with non-autologous cell and gene therapies, and other personalized medicines?
Swistock (UPS): With autologous therapies, the biggest complexity is that, not one, but two really high-performance shipments are involved. There can be challenges, for instance, when the patient visits a facility where blood is collected. Often these trials are run in dispersed locations.
In some cases, there will be fewer labs available to send the blood. In general, with autologous treatments, special planning is particularly important for the journey’s second leg.
Sweeney (World Courier): The obvious main difference is that an autologous cell-therapy scenario involves a circular supply chain, where the allogeneic model is more of a straight line between two points. With the circular supply chain, there is generally more of a need for careful coordination between apheresis and manufacturing slots.
With allogeneic, there is likely more room for maneuvering because it relates to the time between when the therapy is manufactured and the time it is needed for infusion into a patient. The more complex circular supply chain for autologous requires precision planning with no room for error or delays. The straight line supply chain for allogeneic relies on experienced specialists.
BioPharm: What special temperature-control technologies, storage, and transportation options are required for these types of advanced therapies?
Klingelhoefer (World Courier): This will vary on the product and pharmaceutical sponsor requirements. Sponsors often require temperature-controlled packaging for apheresis samples (2-8 C packaging) and packaging for end-therapy product (typically, asking for liquid nitrogen dry shippers). In some cases, customers will ask for global positioning system (GPS) tracking devices to enhance the visibility of their shipments.
BioPharm: Some clinical-trial materials are now delivered direct to patients’ (DTP) homes. Do you see that approach being used in the future for these types of materials, and how would that complicate the overall process?
Swistock (UPS): There is great interest in DTP activity. DTP exists for rare diseases, but the logistics for clinical trials, involving ambient temperatures, are easier. We’ve had success with these studies. Investigational medicinal products must be delivered on a regular basis, typically in one or two doses.
In a clinical setting, they may be delivered less frequently. But if people have mobility problems, DTP studies speak to a patient-centric model we’re seeing the industry lean toward more and more.
Sweeney (World Courier): At the moment, most shipments would be beyond the scope of home coordination. For many situations, the end-therapy product is sent at frozen temperatures, including some cryogenically frozen material, which then requires a sophisticated thawing process before infusion. Currently, it is unrealistic to expect a DTP scenario for most cell and gene-therapy products.
1. IMS Institute for Healthcare Informatics, “The Global Use of Medicines: Outlook Through 2017,” imshealth.com.
Article DetailsBioPharm International
Vol. 30, No. 2
When referring to this article, please cite it as "A. Shanley, "Cold Chain: Zeroing in on the Last Mile," BioPharm International 30."