Autolog Gene Therapies (aGT) have left the status of a vision, instead they become reality. Kymriah (Novartis) and Yescarta (Gilead) already have their FDA approval and are available in the market. How do these treatments work? In a few words: Cells become harvested from the patient. Thereafter, these cells are shipped to a pharma site, become processed, shipped back and re-administered to the patient. But what does that mean for the logistics of such sensitive and life-saving shipments? At the LogiPharma 2018 in Montreux, Camelot introduced the Hypertrust X-Chain. A platform based on blockchain technology, to support and protect the treatment process of Autolog Gene Therapies (aGT) with the utmost respect and responsibility.
What is unique about GT logistics?
First, it is the background of each shipment. Besides the costs for such therapies each shipment is intended to save a human life and the affected patients often have no time for a second attempt. But also from the technical point of view, it is not just a cold chain or an ultra-cold chain. It is a closed-loop supply chain. The patient is the starting point and end of the supply chain.
Throughout the treatment process, the chain of custody must be seamlessly auditable for each process step and each handover.
Risk mitigation already starts prior the transport planning. Each leg of each available route must be assessed for duration and risk rating. There are several methods available to achieve a good risk rating (e.g. Fault Tree Analysis, Event Tree Analysis, Failure Mode and Effect Analysis, Markov Model Chain, Hazard and Operability Study …). During routing and scheduling, the specified route must be validated for duration and risk rating.
Subcontracting is indispensable in the world of worldwide transports. But as a chain is only as strong as its weakest part, that also applies to your supply chain. Every third party who comes into direct or indirect contact with the shipment must be regularly validated.
Packaging and transport units
The cold chain must be maintained under all circumstances. Ensuring this, starts with the right packaging. This includes the usage of validated and certified packaging material.
The static holding time is a good indicator how long a package can keep the temperature below a certain level. The dynamic holding time indicates how long this works when the shipment is in transit. However, this is changing when datalogger become attached, so validation must take this into account.
Data logger are extremely important to detect issues and to react on short term.
Good data loggers report a multitude of parameters in real-time, such as:
- Internal Temperature
- External Temperature
For cryogenic ultra-cold chain shipments, dry shippers are required. These dry shippers must be prepared before use, amongst other things by filling with liquid nitrogen. Liquid nitrogen boils at -196 °C and is used to keep the temperature constant below 150 ° C. Dry shippers are the key element of the cryogenic ultra-cold-chain. Therefore, the lifecycle of a dry shipper must follow a strict protocol. Preparation, use, return, cleaning, maintenance, replacement of consumables, test and revalidation. Compliance with the protocol must be documented at each step.
During transport execution, monitoring is of highest importance. By evaluating data loggers as often as possible (e.g. at every shipment handover), a minimum of monitoring can be created. Wherever possible, real-time monitoring should be used. By using real-time monitoring, problems can be identified in emergence and countermeasures can be triggered immediately.
This type of active monitoring allows interventions and works as follows. In case a dry shipper is upset, this reduces the holding time. An orientation sensor detects the event and reports it to the control tower. The control tower responds and commands the driver to stop, to straighten up dry shipper and to check the load securing. In this way the consequences of the disturbance can be minimized.
Customs clearance is another complex issue. For example, Germany has its own national export regulation of much-needed goods of human origin for life-saving measures. Importing the processed cells involves another party as it may need an import authorization from the National Food and Drug Administration. They will check whether the import complies with the Food and Drug Law, which is a national law. Therefore, it requires some alignments in advance with the competent authorities to exclude any avoidable interruptions during customs clearance.
Hypertrust X-Chain is the platform that seamlessly accompanies the end-to-end process across all stakeholders. It provides tools to help stakeholders and uses blockchain technology to make the process auditable at all times. The integration into the existing IT landscape makes the X-Chain nearly invisible to most end users.