Car-T drug therapies are very complex personalized therapies, not only from the point of view of production and patient management. In fact, like therapy, also the logistical solution must be individual in terms of transport times, storage requirements, temperature control and handling activities.
The different phases that lead from production to administration to the patient require close collaboration between the links of the supply chain and careful management of the product, which can only be carried out through blind observance of Good Production Practices and Good Distribution Practices. In fact, in this case the drug is a unique sample, tampering with which would lead to the failure of the entire therapy, probably definitively, as the conditions of the patients who access the therapy do not always allow for a delay in production and administration times.
A complex life (and transport) cycle
The five phases into which we could divide the therapy cycle see authorized centres, production and healthcare workers interfacing with companies involved in the logistical management of the sample first and the drug afterwards. The first phase of this personalized supply chain begins with the collection of the patient’s T lymphocyte sample. The sample is then prepared for transport from the center to the production facilities: it is transferred into disposable bags and proceeded with cryopreservation and transport by specialized operatorsin the severe cold chain . In some cases, the hospital center has its own pharmaceutical workshop authorized by AIFA for the production of a medicine for advanced therapies. In these cases it is the workshop itself that proceeds to the genetic engineering phase. This is what happens, for example, at the Bambino Gesù pediatric hospital in Rome.
Programming and flexibility
Pickup and transport, both to an in-house facility and to the production facility, imply careful planning of activities. The logistics partner and the production site coordinate the travel plan well in advance and communicate it, indicating exactly the itinerary, car (or flight) number and pick-up and arrival dates, so as to allow the hospital center to fulfill first to administrative obligations.
To fully understand the effort in terms of time and economic resources, it is important to keep in mind that all these activities are implemented for the transport of a single sample.
Once it reaches the production company or pharmaceutical workshop, the sample is brought back to temperature and genetically modified, then the Car-T cells obtained are multiplied to create millions of copies. At this point the drug, ready to be re-infused into the patient, is once again subjected to cryopreservation and stored while waiting for the hospital center to be ready to receive it.
All the operators involved coordinate again on the possible date of delivery and infusion, to plan the itinerary and timing of the transport. This is a very delicate phase, which can undergo sudden changes dictated by the patient’s state of health.
In fact, before the infusion, patients also undergo a chemotherapy treatment aimed at promoting the expansion and proliferation of the Car-T cells when they are infused.
The logistical challenge
These personalized therapies are reinventing traditional flows, imposing increasingly versatile but accurate logistics. When the drug being transported is tailor-made for a single person and starting from their genetic makeup, there can be no margin for error, not only in the management and transport of that product, but also of the information related to it.
This circular logistics process, which starts and returns to the center where the patient is hospitalized, must guarantee: the sharing of information with other operators, accurate planning which is however flexible based on the state of patient health, solid experience in the management and transport of products in a severe cold chain, the tracking and traceability of the sample and the drug at any stage of the process, given the costs and effort associated with the product.
Car-Ts therefore represent a great challenge not only for research, but for the entire pharmaceutical supply chain.
While studies on new areas of application and new strategies are multiplying in Italy, the high costs of these personalized therapies increasingly require standardization in the supply chain to allow scalability.
