This is the third in a series of blogs outlining how to solve the logistics and packaging challenges involved in Cell & Gene Therapy. Read previous blogs in our Cell & Gene Therapy series.
Apheresis is the process of collecting a patient’s (or donor’s) cells, usually T-cells for CAR-T therapies, via a machine that separates blood components and sends the leftovers back into the body. Those collected cells are the starting material for a life-saving therapy, but here’s the catch: they are fragile. From the moment they leave the vein, the clock’s ticking and the temperature’s dropping.
The packaging and transport of apheresis materials, whether from patients or healthy donors, are critical to the success of therapies like CAR-T treatments in the cell and gene therapy (CGT) space. The patient is now a critical part of the manufacturing supply chain, and the logistics challenges vary based on if the apheresis is being shipped fresh, at 2-8°C, or frozen at ≤-150°C.
This is first mile logistics, and it is the most challenging aspect in all of Cell and Gene Therapy as it relates to packaging and logistics. It requires extreme coordination between therapy manufacturers, packaging and logistics partners, hospital staff, and even the patient! Needing to supply a critical raw material for a lifesaving therapy, or any product for that matter, is a new challenge for any industry – but name another business model where you, the customer, supply the critical component(s) for the product you are buying? That shows how unusual this situation is
Shipping Methods: Frozen vs. Fresh = A Strategic Call
Choosing how to ship apheresis materials, whether fresh at 2-8°C, frozen at ≤-150°C, or a mix of both, isn’t as much a strategic play as it is a logistics choice. Each path balances cell viability with supply chain realities and picking the right one means knowing the trade-offs.
Start with fresh at 2-8°C. It’s the king for cell viability, boosting manufacturing success rates, but they only have a 72-hour shelf life. Three days from needle-out to processing, and any snag (patient delays, slow couriers, missed flights, adverse weather) tightens the screws. It’s a narrow window, and logistics can feel like a race against the clock.
How do you keep fresh apheresis in the game? A pre-conditioned VIP insulated shipper with phase-change materials (PCMs), such as CCT’s EcoFlex solution, arrives at the apheresis center primed and ready: nurse drops the leukopak in, seals it tight, and it’s off to the manufacturing site. These VIP shippers with PCMs can hold 2-8°C for well over 100 hours, but once prepped and shipped from the supplier, that duration clock is ticking. If there’s a sizeable delay in taking the sample from the patient, it can feel like the 100 hours is going very fast.
Then there’s the on-demand cooling shipper, activated when the apheresis is packed. With older on-demand cooling technology, it pulls the cells from body temp (37°C) down to 2-8°C, but that energy draw at the beginning can strain its overall duration on the back end in tough spots Newer technology like the Altai shipper, being brought to market with a partnership between CCT and Gobi Technologies, is overcoming these duration and performance issues
Here’s where teamwork shifts the odds. Requalify apheresis stability to 2-16°C, and you’ve got breathing room. VIP/PCM shippers, like the CCT EcoFlex, will last longer; and older technology on-demand units gain leeway as temps creep to 16°Cadding hours of transport to both options as energy fades. Stability studies back it up, proving cell viability holds steady at elevated temperatures out to 72 hours, which can cut non-conformances and deviations, saving time and money on quality records.
The other option is to partner with your suppliers to innovate. Working with customers and understanding the challenges faced with apheresis shipping CCT has created a partnership with Gobi Technologies to gain access to next generation On-Demand cooling shipper technology. Altai has developed On-demand cooling that has an easier pack-out, easier activation and more reliable and durable thermal performance than previous generations of on-demand cooling. It also includes the ability for re-use to support sustainability score cards.
Below is some data from our qualification testing of the Altai which CCT is bringing to market. The thermal performance improvement over previous technologies is significant. The Altai passes with ease the ISTA 7D thermal profile vs. previous technologies which struggle against the much milder ISTA 7E thermal profile. The ease of activation is simple. If you can turn on a light switch you can turn on the Altai. Altai really is the next generation on-demand cooling shipper designed to work in the apheresis first mile logistics space.
ISTA 7D Heat Profile
ISTA 7D Cold Profile
As discussed in the first blog, teamwork is essential. Packaging qualifies shipper duration, Cell Order Management tracks the cells, Logistics plots the route, Process Development nails the science, and suppliers collaborate with their customers and innovate That collaboration turns tight spots into wins.
Then there’s frozen apheresis shipped at ≤-150°C: the long-haul hero. If cells are cryo-preserved, shelf life stretches out, and you no longer have the 72 hour cell viability clock ticking in the background, only the shipper duration clock. LN2 dry vapor shippers hold ≤-150°C for up to 15 days without a pit stop, so a missed flight or packed manufacturing slate isn’t a crisis.
The downside? Freezing cuts cell viability, even with tight freezing controls, and manufacturing successes can take a hit. Most apheresis centers can’t freeze with the precision needed to minimize cell viability loss. Plus, the cost stacks up, thanks to LN2 shipper leases andlogistics with high dimensional weight. Shipping apheresis frozen buys time, but not without a price.
Or there’s the combo route. Here you ship fresh to a Contract Development and Manufacturing Organization (CDMO), ideally near the apheresis site. The CDMO refines it, isolating Peripheral Blood Mononuclear Cells (PBMCs) to prep for manufacturing, then freezes with care to lessen the cell viability drop. From there, it’s ≤-150°C to the final stop.
It’s a great fit for a small company with global patients – say, Europe apheresis, witht U.S. manufacturing. Fresh reaches the CDMO, likely in Europe in under 72 hours; then frozen bridges the distance. It’s more steps and cost, and cell viability dips because of freezing, but the viability loss is less than a straight freeze at the apheresis center, keeping timelines flexible.
Whichever path you take, you’re not alone. This supply chain, with its patient schedule shifts, tight windows and fragile cells, needs partners who’ve been there. Logistics with real-time tracking, suppliers who pivot fast, CDMOs who ace the handoff.
Maintaining Temperature Integrity
In the apheresis game, temperature’s a linchpin. Keep those cells in their happy place (2-8°C for fresh, ≤-150°C for frozen) and cell viability holds predictably steady. Stray too high, and degradation hits the gas, accelerating fast. Where do you really run into trouble? Let fresh apheresis get too cold with an unplanned freeze, and ice crystals turn into wrecking balls, shredding cell walls without a cryo-preservation agent to step in. At least with frozen apheresis at ≤-150°C, you’ve planned it out, allowing agents like CDMOs to cushion the blow, but it’s not foolproof. Ice crystals still form, piercing cell walls and costing cells, just not as brutal as the unplanned freeze-for-all. CGT patients, already beat down by chemo or other treatments, don’t have spare cells to lose, and in reality, neither does the CGT manufacturer.
Why does low cell viability sting so much? Fall below that critical threshold for quantity of viable cells, and you’re left with too few functional cells to make manufacturing work. Stress from apheresis, a drawn-out transit, temperature slips, or rough processing can all take the blame. For CAR-T therapies, it’s a numbers game: each dose needs a minimum of viable cells to deliver the filed therapeutic does. If the final drug product (FDP) misses commercial specs and lands Out Of Specification (OOS), it might still get reclassified as clinical for the patient: a last shot. But here’s the rub: reclassify it as clinical, and the manufacturer can’t charge a dime. When a single dose’s COGS tops $100,000, sometimes ballooning into the multiple hundreds of thousands, that’s a punch to the wallet. Keeping apheresis temperatures locked in gives the patient’s starting material its best swing in manufacturing, and it keeps the bottom line from bleeding red. Logistics isn’t a side hustle here; it’s one of the threads stitching it all together.
So, how do you keep the cold chain from linked and intact? It starts with packaging, forged and validated through a best-in-class qualification gauntlet.
Documents such as PDA TR39, ISTA Thermal OQ Best Practice Guide, ISTA Thermal PQ/PV Best Practice Guide, ISTA Standard 20, ISTA Ambient Temperature Profile Best Practice Guide, and many others.
After the qualification process is dialed in, then look at the thermal profile… is it appropriate for the origin to destination(s) you need? Finally, if the process is dialed, and the thermal profile stresses to the proper max and min temperatures a shipper that is properly engineered will hold steady at 2-8°C or lock in at ≤-150°C for LN2 shippers. If you need some support, partner Cold Chain Technologies (CCT) Technical Solutions. We understand the aphereis process, its criticality to the entire vein-to-vein triangle, and know how to make it all work.
While having a rock-solid process is the foundation to developing the right box, it’s not everything, but it is what everything is built upon. Getting the pack-out right is half the battle. Slap those components in wrong – misplaced PCMs, a cooling engine not activated correctly, missing pieces, or the temp recorder placed in the wrong spot – and you’re chasing excursions, real or not. Redesign that setup, and those “excursions” vanish, because a poor pack-out was leading to false readings. Knowledgeable partners like Cold Chain Technologies (CCT) bring the cheat sheet, thanks too years of seeing it, solving it, and dialing in best-practice pack-outs that cut through the clutter.
Real-time tracking is your next layer, as pinning down a shipper’s spot on the map beats guesswork every time. This is crucial for locating a shipper that has been bumped off a flight or lost in warehouse limbo. Seasoned logistics partners bring the hustle here, and working with logistics partners who know the criticality of what’s being shipped can mean the difference between cells landing on time or a patient facing a second apheresis, if that’s even an option. Again, the real hero is teamwork. The packaging team specs the gear, logistics keeps tabs, couriers smooth the ride, and when an apheresis package goes missing, it takes all three to track it down and set it right.
On top of everything else, there’s the logistics regulatory rulebook. Those leukopaks? They’re flagged as Category B dangerous goods and that means sticking to Packaging Instruction 650 (PI 650), plus GDP and cGMP rules to keep it square. Partners like Cold Chain Technologies (CCT), who’ve run this gauntlet plenty, know how to keep those cells rolling without snagging on the fine print.
Ultimately, the long game is scalability. As a cell and gene therapy company grows, its apheresis collection process has to grow with it. Here’s where trusted partners can deal you a winning hand. Beware so-called solutions that lock their cold chain packaging to one product, not an adaptable platform. Our Technical Solutions team at CCT can set you up product-agnostic from the jump.
Conclusion
Apheresis shipping is pharma’s newest puzzle, a first-mile logistics challenge where patients aren’t just passengers but part of the supply chain, delivering the raw goods. Partners like Cold Chain Technologies bring the playbook to dodge the traps and consistently, successfully send therapies down the line that rewrite lives.