Contract Pharma: Please briefly describe the current state of the cell therapy industry, the biggest players and regulatory climate.
 
Martin Lamb: Interest in cell therapies as the 4th pillar of cancer treatment remains high, as demonstrated by the $16 billion invested between 2015-2016. Cell therapy developers were prominent at the recent major oncology conference – ASCO 2017, with the latest exciting results announced by Novartis, Kite, Bluebird/Celgene and Juno. Autologous therapies continue to dominate, with Novartis and Kite neck-and-neck in the race to be the first CAR-T to market for cancer treatment. While CAR-Ts are dominating the headlines, developers of next generation cell therapies such as those modified by CRISPR/Cas9 gene editing, therapies with built-in on/off switches, different cell/receptor types (TCRs and NKs), are also attracting impressive funding.
 
The regulatory landscape for cell therapy products remains mixed. While initiatives such as the 21st Century Cures Act in the U.S. can be viewed as positives by the industry, the EMA’s Draft Guidance on GMP for ATMPs has received harsh criticism from various quarters, including a strongly worded letter from PIC/S, an international group comprising of Regulatory Authorities from 49 countries.
 
CP: What are the biggest challenges the cell therapy industry faces?
 
ML: Complex, often manual, manufacturing processes requiring skilled operators may limit the ability of cell therapies to scale to reach projected market demand. Current manufacturing processes can also take weeks, which is far from ideal for critically ill or deteriorating patients. For example, in 2016 just over 3,500 patients were treated with autologous cell therapies. This is project to exceed 200,000 over the next decade. Significant improvement will have to be made for current manufacturing processes to match this demand.
 
Cost-of-goods, largely arising as a result of the manufacturing process, is likely to be a challenge for developers and payers alike. A CAR-T therapy is estimated to cost $150,000 for manufacturing alone – the final price to health systems is likely to be more than double this amount. For autologous therapies, there is no economy of scale – each therapy is produced on a per-patient basis.
 
Maintaining quality and traceability of products across a complex, multi-stakeholder supply chain remains a challenge. This is especially true for autologous therapies for which it is essential that a patient’s own cellular material is returned to them for infusion. It may be possible, though resource-intensive, to track products manually during early development when only a handful of patients and sites are involved. However, such a model is unlikely to continue to be effective once products reach commercialization.
 
Cell therapies are ‘living therapies’. Their effectiveness can be impacted by their environmental conditions through the supply chain. Logistics around transferring cellular material to manufacturing sites and back to the clinic for infusion requires stringent temperature controls. As cell therapies globalize, it will be critical to have the ability to transport shipments seamlessly across borders.

Scheduling of activities across the supply chain is also critical in cell therapy. For example, does a clinician know that manufacturing capacity when they collect cells from a patient will be available when the cells arrive? Similarly, patients often require pre-treatment before they can receive cell therapy, so knowledge of the date a therapy will be available for infusion is just as important.

CP: In what areas have advances been made to help overcome these challenges?
 
ML: Development of automated, closed system equipment, such as Miltenyi’s Prodigy system, to manufacturer cell therapies is removing the need for lengthy, highly manual processes executed by highly skilled operatives. Automated systems have the potential to ‘democratise’ cell therapies by increasing the number of operators and centers capable of handling the manufacturing process.
 
The introduction of automation can also reduce the risk of lost products elsewhere in the supply chain. For example, inconsistent thawing of frozen cellular material can negatively impact on product integrity. The introduction of automated thawing devices can reduce the risk of product loss during thawing.

IT solutions have been developed that provide support in these areas by tracking product quality across the supply chain. TrakCel’s platform provides full needle-needle tracking of cellular material, includes an integral scheduler to support alignment of supply chain activities, and gives cell therapy developers the ability to incorporate product-specific workflows into the system ensuring all those involved in the supply chain execute activities in a consistent, compliant manner. Furthermore, the platform’s integration with third party systems, from logistics providers, manufacturing sites to clinics, provides a full end-end view of the supply chain, allowing points of failure to be identified and processes optimized to seal off and prevent future issues.
 
Cryogenic freezing technologies are also improving. For example, cell preservation media designed for cryogenic freezing can help reduce cell loss as a result of this process. Advanced cryogenic shipping systems, such as Savsu’s EVO shipper, are helping control risk of loss during shipment by allowing real time tracking of temperature and location. Cryogenic freezing of cells can help introduce some flexibility when scheduling patient treatment.
 
CP: How do technology solutions play into various stages of cell therapy development, manufacture and delivery processes?
 
ML: Technology plays a critical role throughout the cell therapy delivery process, and will grow in importance as cell therapies are commercialized. For example, patients identified as suitable candidates for cell therapy can be captured in patient registries or systems such as CRM. Once commercialized, and given the likely high price of cell therapies, payers are likely to need to approve patients for treatment before this can begin and this process can also be system based.
 
Once the patient begins treatment, it is necessary to assign a unique identification to the patient, which will be used to track their cells throughout the supply chain. Established systems such as ERP, MES and QMS can be used to track the product’s process through manufacturing and logistics, with systems such as LIMS used to capture analytical test results to verify product quality before it is deemed suitable for use in patients. Equipment itself can capture data critical to a treatment’s integrity – for example, cell count and start/finish times.
 
Finally, once a therapy is commercialized, payment models for these expensive treatments are likely to involve long follow-up periods, which are also likely to involve capturing key clinical milestones through IT systems such as EDC, ePRO and treatment centres’ own systems.
 
While technology supports the entire cell therapy delivery process, it is important to note that this data is currently captured by separate systems. It is becoming steadily more important to provide cell therapy developers with a full end-end chain or custody report covering what was done, what material was used, when and by whom it is essential to implement a system that combines data from these disparate sources. This can provide product owners, physicians, regulators and patients with confidence in the quality of the product before it is used. Moreover, capturing this data in a single system gives cell therapy developers the opportunity to use data to optimize their processes, favourably impacting on the cost of goods. It also means they can concentrate resources on what they are, by default, good at – developing cell therapies, and not using crucial resources on logistics.