Safeguarding the Chain of Identity with Cell and Gene Therapies

As well as looking at the potential promised by cell and gene therapies , the industry meeting earlier this month evaluated the logistical challenges presented by these treatments. The niche supply chain hurdles are imposed by the unique logistics infrastructure required by cell and gene therapies (Patient > Manufacturer > Patient). Sascha Sonnenberg, President of Global CTD Sales & Operations at Marken presented a session on this topic at this years Cell and Gene Manufacturing Conference.

The dominant consideration is to, of course , transport the right product to the right patient at a reasonable cost of goods. For this the location of the patient population in comparison to the manufacturer is pivotal. The delicate stability of the products which require tight turnaround times and their expensive price points means that mistakes in logistics cannot be afforded. In executing transit correctly and efficiently attendees at the meeting considered whether patients should be brought to the production site rather than the cell to them. It was mentioned, however, that some subjects requiring these treatments are in critical conditions and so international travel is not always an option.

Local infrastructure

Local infrastructure is relied upon heavily in the production of these therapies so the regional capabilities of airlines and airports need to be considered - flight connections, frequencies, seasonal operating patterns, loading capacities and shipping and storage restriction considerations. For example, if dry ice is being shipped there could potentially be restrictions, the pilot is in some cases allocated with making this decision. If the shipment is unloaded then process would need to be restarted and materials could be lost. QP release when importing to the EU can cause delays in transport and cause materials to be lost.

Partners & stakeholder support

The location of sourcing partners for materials is another factor to account for the process. Also, their capabilities and experience to support producers needs to be assessed as cell and gene medicines are complex to produce and transport with their individual requirements. Training may be needed for partners on this front for instance to avoid non sterile raw material, microbial contamination - suppliers need to be audited and quality agreements need to be agreed upon.

Partners need to support in managing the chain of custody and identity through constant communication. With separated communication channels, there is a danger that information could be missed like upgrades in packaging requirements. Some firms use procurement as a template for biosample handling.

Logistics Systems

Documented lane verification and administration for transit and customs clearance timelines are very influential on the success of transporting a cell and gene therapy.

With the handling of systems, authorization of access to systems needs to be delegated. Automation should be applied wisely to aid workload without harming the precision of efforts. Firstly, obtaining n enhanced level of visibility with integrated systems is needed to leads to automation. Ordering tracking and system interfaces can assist with the transit of these products.

The reverse logistics attached to some temperature control containers and dewars can act as a large blockade for some pharma firms. With closed loops being a necessity, reverse logistics apply additional costs and operational burdens.

In response to this effect on a pharma firm Jeroen Janssens, Senior Manager, Vaccine Distribution & Cold Chain, GSK Vaccines reminds: “We are here to manufacture pharmaceutical products, not to organise logistics flows of empty containers.” In response to this sort of opinion and with greener cold chain packaging solutions rising in popularity, the suppliers of these packaging solutions, or even LSPs, have started to include the reverse logistics in the rental costs for units.

One attendee at the event noted that volumetric changes could be made to the packaging of the therapies to reduce cost burdens on the supply chain. Ancillary investments can be applied to incur savings in the overall shipment for example using plastic instead of glass vials can make significant savings. Especially if thousands of shipments are being made.

In regards to contamination requirements, packaging needs to maintain the stability of the product and have the ability to be frozen. Contamination control should apply sterile over wraps on the therapies as well as validating the stability and integrity of thermal cycle and cleaning the containers used for transit.

Contamination can occur at any stage. One case discussed at the conference noted the presence of a bug living inside the wrapper of an iVbag which was found to have infiltrated the product once it gained entry into the critical production area. It was said that there are improvements needed in the industry concerning conflicts on how contamination is handled with policies and procedures by the bedside.

Materials

The longer the stability is of the product’s materials, the greater the delivery flexibility. In Sascha Sonnenberg’s session it was noted that the product stability in fact directs the distribution and manufacturing strategy. For instance, in the selection of a centralized single site model or a multi site approach. This also stretches to the temperature management solutions chosen. Perhaps by avoiding liquid nitrogen or dry ice can to manufacturers can sidestep adding weight and costs later on. He added that it’s important to remember with cell therapy it isn’t about shipping, but handling a chain of identity and custody so that materials are maintained.

In preserving the chain of identity, firstly, materials need to be qualified and validated, therefore the suppliers will need to be audited also. Contamination of the designed cells can occur at any stage. Qualification must start with the raw biological material. Samples of material need to be tested at procurement. Quality of what is being put in needs to be assessed as well as the final packaging to see if it is suitable for the product’s life cycle and process. A slip up in this area can have adverse consequences. The whole process should be designed to ensure that the product has the most minimal risk of contamination.

Commercial Scale-up & Scale-Out Considerations

When going commercial with a cell and gene therapy, members at the conference noted that it would be a mistake to view it as a brand new supply chain. Instead, scaling up, scaling out and the robustness of the supply chain need to be considered from the primary stages. When scaling up the additional weight incurred by the therapies is a significant change has a large influence on budget. It was mentioned that manufacturers can expect 60% of budget to go on to the logistics of the cell and gene therapy.

Automation is very productive for the commercial scaling up stages. System integration is similarly important when uplifting volumes. This will ensure that the right cells are transported to the right patients with a reasonable cost of goods.