In a previous post, we outlined how your contract development and manufacturing organization (CDMO) can help you avoid supply chain problems and ensure your project stays on track. In this post, we learn about some of the current issues impacting the manufacture and supply of cell and gene therapy (CGT) products.
Manufacturing and shipping costs
CGT is a relatively young industry, and products are expensive to manufacture. The “one and done” (one dose or treatment) nature of these therapies means that even with the high price tag, CGTs could be more cost-effective and less resource-intensive on healthcare systems than many of the traditional treatment options available for long-term chronic conditions. At current prices, however, healthcare systems will not support their licensing, meaning CGT costs must come down.
Shipping is one area where savings can be made to reduce the final price tag. CGT products are expensive to transport, and this is a function of the supply chain – both upstream and downstream. As the industry matures and clinical adoption grows, volumes and efficiencies will increase, which will drive down shipping costs.
Standardization also plays a role in shipping costs and will hopefully drive down expenses in the future as standardization increases. Different companies have different systems, equipment, and primary containers, which impedes standardization, making it difficult to automate processes and create efficiencies. Fortunately, standardization is already moving into the supply chain.
As CGT uptake increases, there is a need to scale up production to meet the demand. Upscaling is difficult with advanced therapies, just as it was difficult for the pioneers of monoclonal antibodies to upscale nearly 20 years ago. Herceptin (used to treat HER2-positive breast cancer), for example, is one of the most successful monoclonal antibodies in history. Its launch was supply-chain constrained, and physicians could not access enough of the drug to prescribe to patients, creating a major challenge for both groups. In the CGT field, the key is to quickly identify and address these issues to prevent this type of situation. Scaling out for autologous products and scaling up for allogeneic products is as critical as cost reduction.
In the future, the emergence of hybrid systems with centralized manufacturing, decentralized local storage, and a “last-mile” distribution facility could bring the CGT industry the required efficiencies to scale effectively. Process developments, such as the ability to freeze source materials at the point of accession, can also help by providing some breathing space in getting materials to a facility on time to easily schedule manufacturing.
The pandemic has demonstrated the fragility of the global supply chain and increased societal awareness of the issues. Executing a vaccination campaign is incredibly complicated and involves managing different storage conditions for mRNA vaccines. This has increased interest in mitigating supply chain risk.
Just-in-time manufacturing works but, as we have seen, it can fall apart very quickly. It takes significant quantities of materials to manufacture one dose of autologous or allogeneic therapy. Each ingredient has its own supply chain peculiarities. It’s difficult to plan ahead of time in manufacturing when certain components have lead times of nine to 12 months, especially when products have limited shelf life. Put simply, you cannot buy a year’s worth of material when it has a three-month expiration date.
The pandemic will have long-term consequences on global supply chains. Consider the impact of the shortage of (and growing demand for) semiconductors. Every step in the manufacturing and logistics of selling CGTs involves equipment that depends on semiconductors. This has led to delays in manufacturing in everything from vehicles to devices used in CGTs and data logger devices used to track and trace shipments worldwide. This has changed how companies plan, schedule, and look at their inventories.
The pandemic also caused an almost immediate and nearly complete shutdown of hospital-based clinical trials. The medium-term effect was an irrevocable one- to two-quarter delay in clinical programs for many therapeutic clients.
Now, however, the industry is benefiting from unexpected tailwinds. First, there is mRNA-based vaccinology – one of the most significant advances since the 1950s when the SALT polio vaccine burst onto the scene. Second, there have been significant increases in the funding and execution of biomedical research. The future for the CGT field looks bright; according to the Alliance for Regenerative Medicine, there will be more than $20 billion in funding for the field this year.
Contact us to learn more about how our supply chain expertise can help in the manufacturing of your CGT. You can also listen to a podcast examining this topic. Search “Commercializing Living Therapies with CCRM” on your favourite podcast player or visit our podcast.