TrakCel recently announced the launch of its latest platform. Paul Viggers, Chief Commercial Officer at TrakCel, explains how it fits into the drug discovery and development sector.
The catalysts
Ten years ago, cell and gene therapy (CGT) was really finding its feet as success stories such as that of Emily Whitehead began to hit the news.1 Emily was a seven-year-old girl who relapsed a second time following two years battling leukaemia, out of standard treatment options, and her life was saved by a CAR-T treatment in early clinical trial. The story was rightly hailed as a new era in medicine as Emily and her family still campaign for better access to advanced therapies for more children as Emily celebrates her tenth-year cancer free.
Even ten years ago, the supply chain process for drugs like those used to treat Emily was incredibly complex for several key reasons. Firstly, the patient became part of the supply chain as cells collected from them are required as the fundamental raw material on which the treatment is based. Personalised products within healthcare are not a new thing, with prosthetics and dental bridges being common examples, but these do not experience the other complexities that live cells do, namely that of storage conditions and viable life. They also do not have the potential of causing a severe immune response if they are administered to the wrong patient. As such, there was little in both the traditional pharma and medical device supply chain processes that was a good fit for advanced therapy developers.
This was in fact highlighted in 2007 by the FDA in the CMC (Chemistry, Manufacturing & Controls) review2 for Dendreon’s Provenge, an autologous therapy targeting prostate cancer, citing that logistics would be a major challenge due short shelf life, manufacturing schedule, time restrictions, quality control and complex shipping demand that together would require ‘substantial attention paid to coordinating and orchestrating these events.’ It took a further three years from this point for Provenge to be approved, with the FDA stating that the absence of information through the supply chain to ‘determine that the facility in which the product is manufactured, processed, packed or held would ensure the continued safety, purity, and potency of the product’ as a primary reason for delaying the approval3.
Next steps
At this point, it became clear that better tracking and visibility of personalised advanced therapies was required, and both therapy developers and software developers began to explore cell orchestration solutions (COS) that were designed to track each patient’s cells from the point of extraction, throughout shipping and manufacturing, back to the point of infusion. The primary purpose was to create a full audit trail of the supply chain and offer a strong chain of identity (COI) to show specifically which patient the cells belonged to (whilst adhering to data privacy regulations) and chain of custody (COC) documenting responsibility for the cells at each part of the process as well as shipping and storage times and conditions.
15 years later
Over the fifteen years since cell orchestration was identified as being necessary, the profile of the industry has changed beyond recognition. The number of therapy classes in development has exploded as research has advanced methods for tackling a vast array of genetic conditions and diseases in both rare disease and common indications. This change in science demands a change in the supply chain to match. In these therapies, the process is the product and without each step taking place exactly as specified, in the correct order and timeframe, these treatments cannot be reliably produced and delivered to patients.
The challenges of each of these therapies vary hugely, and can involve multiple collection cycles, multiple administration cycles, separate cell samples such as blood and tumor samples to be processed through different processes in tandem, associated to the same patient ID or even tracking of data exchanges such as genetic profiling information. These processes can be difficult, and high-risk to manage manually, the patient volumes through each site (e.g., apheresis centers) may be low, making them reliant on staff performing unfamiliar, complex processes accurately and efficiently. Increasingly, next generation COS uses workflows, screen layouts, data validation, and notifications and prompts to guide users through these steps, to prevent errors and keep them running to time.
Differentiation in process is not limited to therapy class, but also impacted by development stage and target indication, patient population size and distribution impacting the supply chain and the diversity of the partners within it. In early clinical trials, a broad indication therapy may have sufficient patients and supply chain partners locally, but this changes on scale up to commercial approval. The COS must adapt to accommodate resulting changes, ideally without altering the elements that were submitted within the BLA filing.
The impact for COS developers
Requirement to customise to a precise process and be able to expand or change as needs change is the first hurdle encountered by both in-house and commercially developed COS systems. Solutions reliant on custom written code are expensive and unwieldy to maintain for both the customer and the supplier and this has seen a move towards established cloud-based platforms that facilitate agile change as needed, reducing redeployment and retraining costs. An example of this is TrakCel’s second generation COS, OCELLOS.
Another key demand to manage growing CGT supply chains has been integration. As more supply chain systems have digitalised, an integrated environment where real-time information is exchanged between systems, minimising transcription errors and data processing resource is increasingly expected, for example courier progress updates and alerts. This is now an everyday concept and is vital in COS, where a few hours delay can make the difference to a product remaining viable.
The latest generation of products in the COS arena are increasingly utilising common connectivity methods such as API (Application Programming Interface) technology to expand the range of systems that they can integrate and exchange data with. This burden of connectivity generally sits with the developer and COS provider as the central source of truth, capturing full audit history as well as the critical COI and COC records.
The adaptability of COS
The ARM (Alliance for Regenerative Medicine) H1 2021 report showed that the CGT industry is maturing quickly, noting that there are now 243 trials that are in Phase III trials and the 2600 plus CGT trials underway worldwide are controlled by only 1195 developers4. This is a hint at the deeper pipelines that are being developed within the sector, trialing therapies against multiple indications or patient groups, pipelines of therapies based on specific techniques or different therapy classes. Creating a single COS to manage the entire pipeline is critical at an organisational level but must facilitate users throughout the supply chain switching between therapies or patient groups relevant to them, with assurance that the steps that the system is walking them through are correct.
Case study
The cost of a process failure on these therapies is high, as is the resulting pressure on actors within the supply chain. TrakCel recently supported a client through a labeling change deployed through the COS for compliance and control reasons. In this instance, the live shipment in progress at the point of change was for a patient who had had six collection cycles over 18 months to be able to make their dose, which was due to expire in a few weeks. The pressure on the teams dealing with these therapies is immense; and reliable, automated orchestration that proactively manages processes and keeps therapies on track is critical.
Therefore, it is critical for COS developers to focus product development on the needs of the industry, and this is why our latest software release was primarily centred around catering to therapy developer expansion.
Partners and patient locations
Another trait of commercialisation tends to be global spread over different supply chain partners and patient locations. At this stage, there needs to be consideration of how the therapy can be managed through different languages both in terms of product labelling and system requirements and how to facilitate accurate scheduling across different time zones and regulations. For a product that may have a very tight shipping and receiving window, mistakes that result in delays of hours as opposed to days are critical.
This sort of issue has been openly discussed when considering scaling CGT supply chains from clinical to commercial, as the longer supply chain for CGT vs traditional pharma can lead to knowledge gaps. For example, in Saudi Arabia generally, goods can’t be received or cleared through customs on a Friday either, for traditional pharma this may not be an issue but for CGT supply chains it is critical and traditional pharma may not be experienced in this last mile distribution to a pharmacy or a cell lab.
As a result of this type of challenge, COS product development had been heavily led by the needs of an industry consistently headed towards scale up and managing complex international logistics. With a view to using system driven workflows and processes to remove the ownness from individuals when managing diverse rule sets. The result being that COS systems have become important automation tools as well as the COI, COC and audit platform that they started out as.
Looking forward
Technology is another field that moves and develops quickly and when paired with an industry that is by its nature at the cutting-edge of science, developments unfold fast. Technologies such as AI and the resultant forecasting and critical path analysis and failure analysis hold great promise within the sector and this needs to be considered as the available data pool related to CGT supply chain grows.
Another area that is becoming more relevant to the COS space as therapies commercialise is looking at better patient care and services and supporting developers with complex remuneration models. These systems already focus on optimising the quality, safety and speed of treatment within a therapy journey and are now beginning to explore links into patient services such as benefits verification, accessibility assistance and even updates and support during and after the treatment process in order to support the scheduled reimbursement models that are becoming increasingly common due to high cost of treatment.
About the author
Paul Viggers has spent 15 years working within the Life Science Industry providing leadership in both Clinical and Commercial Business Development. Viggers joined TrakCel as SVP Business Development early 2021 having spent 10 years within Business Development at a leading Clinical Supplies company and has since moved into the role of Chief Commercial Officer.
References
- https://emilywhiteheadfoundation.org/our-journey/
- http://wayback.archive-it.org/7993/20170722071307/https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm210012.htm
- http://wayback.archive-it.org/7993/20170723023829/https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm210037.htm
- http://alliancerm.org/wp-content/uploads/2021/08/ARM-H1-2021-Report.pdf
