Increasing demand and regulatory approvals are boosting the manufacture and commercialization of cell and gene therapies, but what are the challenges affecting their supply chain? What preparations need to be made for effective delivery of these advanced therapies at national and global scales?
We asked three experts who will all be speaking at Cell and Gene Therapy: Bioprocessing and Commercialization (September 9-12, 2019, Boston) for their insights on this subject:
What supply chain issues are faced by cell and gene therapies?
Chad Presher: Supply chains are complex for all pharmaceutical products; however, gene and cell therapies face additional challenges. These include regulatory compliance, time and temperature sensitivity, chain of custody, information availability, scalability, and patient demand. In short, all elements of the supply chain must be perfectly synchronized because cell and gene therapy treatments often come with strict time limits for transit, collection, and delivery to the patient. 100% perfect order fulfillment is paramount to patient’s lives. This is of supreme importance in the case of autologous cell therapy treatments in which the patient’s own cells are harvested, transported to a manufacturing site, edited, and returned to the hospital for reimplantation into the patient.
Jason Acker: Stabilization of the cell and gene therapies at low temperatures is one of the most effective methods to extend the time available to complete required infectious disease testing, product characterization, lot release testing, recipient matching and shipment to the recipients. Current cryopreservation methods do not adequately address the variability that can exist in products due to donor or manufacturing variabilities. Ensuring that the quality of the cryopreserved products is high and that low cell loss occurs is critical to being able to achieve the desired clinical outcomes. Little attention, unfortunately is paid to the impact that upstream factors have on the cryopreservation process which typically results in a reduced or sub-optimal recovery of high quality cells following the cryopreservation process.
What are the major challenges that need to be addressed within the downstream processes?
Chad Presher: The storage and movement of most cell and gene therapy products occurs at ultra-low or cryogenic temperatures. The products are typically frozen to these temperatures almost immediately following manufacturing thus limiting labeling options. The aforementioned low manufacturing yield of most products further limits the capability for handling post freeze because of limited freeze and thaw stability data. The amount of material produced per manufacturing operation is so low that it is often not possible to perform testing beyond what is required from a safety, regulatory, and compliance perspective. This creates increasingly difficult conditions for supply chain professionals to ensure 100% perfect order fulfillment.
Jason Acker: Shipping and handling of cryopreserved products continues to be an under appreciated area where product quality is dramatically affected. Transient warming of samples from subzero storage temperatures can and usually does result in ice crystal damage to the cell therapies. Minimizing transient warming using improved cryopreservation technologies or equipment can significantly contribute to improve patient outcomes.
What technologies are there to relieve some of these issues?
Jason Acker: Advances in product storage technologies and sample handling (ie. coolers and thawing devices) have been very important in minimizing the damaging effects of transient warming injury. Efforts to develop DMSO-free or protein free cryopreservation solutions continue, but most products do not produce the same outcomes or require specialized cooling / thawing protocols for optimal results which are not well suited for high-throughput cell manufacturing.
Anna Outhwaite: As this sector matures, there are many companies now beginning to develop technological solutions to address the complex issues with cell and gene therapies.
Under development within our centres are technologies covering material handling, traceability, logistics and control parameters for different types of ATMPs, so they can be managed and documented electronically. This includes the provision of an end-to-end cryochain solution using hardware systems that ensures cell viability and preservation of ATMP products.
We also have a programme to develop technology in development to understand the patient experience using remote technology to assess the effect of novel cell therapies on both patient symptoms and quality of life.
How can scalability of the cell and gene therapies supply chain be best achieved?
Chad Presher: Cell and gene therapies often target rare disease indications. Clinical trials for rare disease face additional difficulty finding patient populations. As such, clinical studies may need to involve hospitals and treatment centers in many different countries. Given the limited supply availability, supply chains must be designed to offer maximum flexibility to meet global demand. This task can be complicated considering the requirements for the handling of biohazardous products. Shipping and customs declarations must be correct to avoid shipping delays. All sites must be prepared to handle biohazardous material and must meet an additional regulatory burden prior to beginning the trial. These complexities also apply to commercially approved therapies that are classified as biohazardous.
Anna Outhwaite: Currently [the Cell and Gene Therapy Catapult is] working with a small number of NHS hospitals who are acting as exemplar centres, investigating solutions to the issues faced when it comes to supplying and administering ATMP. As we move through the programme, we will develop standard practices that can then be tested within other hospitals and then rolled out more widely.
Another focus is the long-term development of the workforce in the UK. The Cell and Gene Therapy Catapult in partnership with MMIP, with £1.5m funding from the Industrial Strategy Challenge Fund, has established an ATMP apprenticeship training scheme with the aim to build the skills base needed to develop the UK ATMP industry. The UK Advanced Therapy Treatment Centres (ATTC) Network is also working to create educational resources for clinical staff to ensure they are equipped with the necessary knowledge of these therapies for use in a wide variety of indications.
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