Moving Beyond Clinical Manufacturing

As of 2021, around 20 cell and gene therapy (CGT) products have reached the US market (1) – and the field continues to expand rapidly, despite the COVID-19 pandemic. By 2025, 10–20 Biological Licence Application (BLA) approvals are expected by the FDA per year  and nearly 10 times that number of Investigational New Drug (IND) applications are expected (2).

Though progressing to the BLA or Marketing Authorization Application (MAA) submission and approval stage is reason enough to celebrate, the challenges of providing the market with a regional or global product have only just begun.

Current methods for delivering CGT products to patients use variable entities and systems that require multiple levels, flow paths of information, and material at numerous process touch points. Cell therapy, specifically autologous cell therapy, arguably lays claim to the most complex and segregated product lifecycle, due to the requirement for the product-receiving patient to also serve as the donor of the product-starting material. This results in a concept referred to as “just-in-time” manufacturing. 

This new concept poses many challenges. The patients are often undergoing treatment for an advanced stage of cancer or other critical illness, but to ensure success of the product, the patients must remain directly involved in the supply chain process. This means traveling to the clinical facility, undergoing the tissue collection process, and then subsequently receiving treatment while the tissue is transported to the target location for manufacturing and release. The entire process may take weeks or months before treatment is available for patient administration and for those patients with critical indications, that’s time that may not be available. 

Just-in-time manufacturing processes give rise to a variety of pain points throughout the chain of identity (CoI) and chain of custody (CoC) pathways and these supply chain issues can sometimes be underestimated as companies typically focus so heavily on successful manufacturing of the product. The issue is understandable, as the general system is set up for products to be developed in a staged approach, focusing on specific deliverables as the product moves through its lifecycle and associated clinical phases. Drug products that target common indications do not procedurally require automation for scalability until later phases, when the demand forces scale up to be initiated. While the initial focus is on safety, quickly followed by product efficacy, I believe there should be an increased focus on the commercial viability of the product at a much earlier stage. Yet again, this is an overlooked aspect of manufacturing. Developers should be asking three key questions: i) Is the manufacturing process a closed-system with reduced touch points? ii) Are the analytical methods validated to accommodate the target release criteria and period? iii) Is the process bill of materials (BoM) streamlined to limit external costs? The right answers to these questions will help establish low cost of goods (COGs) for the product but, no matter how robust the process is, if the supply chain process to achieve just-in-time manufacturing cannot bear the weight of the market, then your product is going nowhere – figuratively and literally. 

There are not many fully integrated service offerings in today’s market that can assist in industrializing and streamlining supply chain logistics with full traceability throughout CoI/CoC processes, let alone at the scale demanded by common oncology indications. To attack the commercialization pain points and establish a robust, reproducible end-to-end process, one must understand both the market need for de-risking the processes from material collection to delivery of the therapy, and the available services that currently support the industry. As the CGT industry grows and matures, service providers are emerging to help with the challenges. Large-pharmaceutical companies such as Novartis and Gilead – as well as CDMOs such as Lonza – have supplemented their capabilities by using clinical management companies (for example, Be The Match Biotherapies) and logistics companies (for example, Cryoport) capable of linkage via an orchestration platform (for example, Vineti, TrakCel, Salesforce).  

Integrated solutions provide a de-risked approach for cell therapy products using full vein-to-vein traceability and allow for streamlined communication by linking all process points through one potential point of contact. The result is a resolution for the more common pain points (logistic delays, process variability, scheduling adherence, compliance issues, and scalability) by allowing the integrated partnership to focus on the pain points specific to their area of expertise. Thus the “jack of all trades, master of none” stigma is banished.  

Right now, the CGT industry is locked into severe supply chain constraints. We must overcome these as an industry by evaluating the processes used and the partners available to help in creating a streamlined vein-to vein service offering. In our industry, nothing is more important than the recipients of the products, and focusing on supply chain today will absolutely benefit the patients of tomorrow.