The approval of Novartis’ Kymriah (tisagenlecleucel) this week heralds a new era of personalised medicine, and – if Gilead’s $11.9bn Kite investment pays off – soon two chimeric antigen receptor (CAR) T-cell therapies could be available in the US.
But such products require a far more complex and time-critical supply chain than mass produced biologics, and – according to Cardiff, UK-based cell and gene therapy focused logistics and tracking company TrakCel Limited – could leave some developers unprepared.
“CAR-T is an autologous therapy, as personalised as therapies get – the patient is part of the supply chain because a CAR-T therapy is produced from the patient’s own cells,” CEO Ravi Nalliah told Biopharma-Reporter.
“It is critical that the cellular material produced from one patient is only used to treat that patient. This requires a higher level of tracking than other cold-chain products that are not patient-specific.”
Real time production
CAR-T products are made by collecting a patient’s cells through apheresis at a specialised clinic before shipping them to a manufacturing site where they are modified, expanded and tested. These are them shipped back to the clinic and infused into the patient.
The process is done “in real time and usually include two or more logistics ‘legs,’” Nalliah said, taking around 22 days for Kymriah, and 17 days for Kite/Gilead’s as-yet-unapproved therapy axicabtagene ciloleucel (axi-cel).
For the product to succeed under such timelines, drugmakers must therefore co-ordinated closely with their third-parties, he told us. Cells need to be collected on a day when capacity is available to conduct downstream activities, logistics providers must be given notice of when cellular material needs to be collected, and manufacturing sites need to know when material is coming so they can block capacity accordingly.
“Cell therapy products are living drugs and their viability is highly sensitive to environmental conditions and handling throughout their supply chain. While this may be true of other temperature sensitive products, the major different with CAR-Ts is that if a treatment is lost, it is not possible to send a replacement from stock.”
Selecting a third-party
While all logistics providers can offer the transportation of products from A to B at a controlled temperature, “given the ‘one chance’ nature of CAR-Ts and their high value, our experience is that the majority of cell therapy developers are willing to pay extra for the personalised service offered by premium couriers,” Nalliah said.
Novartis signed a three-year deal with Cryoport in July for cryogenic logistics support of Kymriah (known then as CTL019) between its manufacturing facility in Morris Plains, New Jersey and its 35 treatment sites.
However, “a lot of CAR-T developers will not have Novartis’ resources,” Nalliah said. And “even Novartis is only going to use 35 treatment sites, and thus complexity associated with product and logistic supply cycles for these limited number of sites still limit availability of products.”
He added Novartis must now demonstrate it can manage complex supply cycles and “other companies will be closely scrutinising how supply cycles are managed to be able to ensure patient safety and manage delivery to all these patients.”