How novel processing platforms incorporating new technologies can help to accelerate the development of cell and gene therapy processing, overcoming key industry challenges including protecting sterility and product integrity.
Cell and gene therapies (CGTs) offer the potential of a one-and-done treatment for many common diseases, as well as those which have had limited treatment options to date. With the added benefits of enhanced targeting capabilities and reduced side effects, CGTs offer huge promise for patients globally. We have already witnessed therapies for spinal muscular atrophy, B-cell lymphoma and ß-thalassemia reach the market, to name a few, and the market is continuing to grow, projected to reach US$ 62.5 billion by 2032 at a CAGR of 22.8%.1
However, this promise does not come without challenges. These therapies are fragile and have complex processing requirements in order to ensure quality and safety for patients. This brings additional costs, on top of the already expensive and time-consuming drug development process. The average cost to develop a new therapy stands at $1.3 billion,2 and takes over a decade. Gene therapies are already passing the $2 million per dose mark.3 With the goal of reaching patients in need, the accessibility of these therapies remains a challenge for the biopharma industry.
Despite thousands of advanced therapy medicinal products (ATMPs) in trial stages, only 32 are FDA-approved4 and 25 are EMAapproved.5 Many more ATMPs, such as CGTs, are now entering the commercialisation stage. New pressures emerge as developers embark on this next phase with the need to meet stringent compliance standards and ensure the very highest quality and safety levels, all while consistently driving down costs.
Following the rapid development and distribution of the BioNTech and Moderna Covid-19 mRNA vaccines, there was promise that learnings around production and manufacturing could be transferred to the advanced therapy industry. ATMP platform technologies are utilising these learnings to deliver efficient manufacturing solutions by incorporating flexible systems with modular designs while increasing automation and digitalisation. The industry is collaborating to find solutions for some of the most challenging manufacturing challenges it has ever had to face, and it is an exciting time to be involved in CGT production.
Why so Challenging?
Small but Mighty
With traditional therapies that treat large groups of patients, the scale of production can be used to reduce costs, and cost is shared among a wider group. CGTs are often targeted to treat small patient populations, with small batch sizes. Small batches require single-use fermenters; for autologous treatments like CAR-T cell therapy, this might be one fermenter per patient with a complete upstream singleuse fluid pathway. This costly approach is necessary to prevent contamination and protect product integrity. With patient safety a priority, this robust approach is imperative, especially as every wasted millilitre could lose thousands of dollars.
Simply the Best
The biological nature of CGTs means they are fragile and must be treated gently throughout production to protect their functionality, as they rely on retaining their complex structure to function successfully. Efficient production relies on high performing systems including pump technologies, but some pumps can cause large pressure fluctuations that lead to damage to biologics. Low shear pumps are specifically designed to minimise this potential damage, but they also need to meet required delivery rates and offer precise control to be commercially viable.