Standardizing CAR-T therapy - Getting it scaled up!

The fields of gene and cellular therapy such as CAR-T and CGT therapy, are characterized by continuous development alongside rapid growth. This brings with it certain challenges, not least in terms of scaling up from naturally small lab environments employing just a handful of scientists to commercial use and bulk production. 

During development and testing, the focus is - as it should be - on efficacy, potential side effects and other criteria that are vital when it comes to the composition and testing of new medical agents and CGT or CAR T cell therapies. Only once a therapy or compound has been approved, scientists as well as manufacturers are faced with standardizing CAR-T therapy and other compounds.

This is when the issue of scaling up to potential mass production as well as logistical questions become acute. It is also where flexible and independent solutions are required and where single-use technologies are the answer: They can be scaled up relatively quickly and easily to meet different needs, which also means they can be integrated in various already existing environments.

Car-T Therapy - the challenges in scaling up to commercial manufacturing

As already mentioned, scaling up to commercial manufacturing poses one of the major challenges when it comes to CGT and CAR T therapy production. A growing number of products - including blockbusters - are entering the global market and the constantly increasing demand does not help in diminishing this potential bottleneck in an otherwise well-oiled and smoothly running system.

In order to remain competitive on the market by turning out large volumes of product, manufacturers need to streamline and simplify the transition from lab and mass production. It is high time to reconsider the design and set-up of this major interface and to allow for an easy scale-up.

The following illustration will show you in detail the solution for the CGT industry by using Single Use Supports technologies.

Areas where CAR-T production faces problems

The challenges in a constantly evolving area such as bioprocessing are manifold, even more so when it comes to novel approaches and newly developed therapies:

• Inefficient and costly production: In terms of manufacturing, most CGT and CAR-T therapies differ from established small molecule and biologics platforms. They are predominantly autologous, which means they are using the patient’s own cells and are manufactured on the basis of one patient per time.
• Low degree of automation: Most cellular therapy manufacturing involves cell culture technology with low levels of automation, thus requiring manual handling of cells at many stages. More often than not, processing is performed in so-called open systems with lower levels of sterility and aseptic fluid transfer than conventional or so-called closed systems, which utilize connected and sealed process lines.
• The need to scale up: Cellular therapies usually require relatively large amounts of cells. However, even if scaled up to larger bioreactors, allogeneic manufacturing has its limits. Similarly, large amounts of viral vectors are needed for gene therapies, while even 1000 L bioreactors often only produce enough for a handful of patients. 
• Shortage of manufacturing facilities: With a shortage of manufacturing facilities, including process lines, for cellular and gene therapies there is currently a significant shortage of relevant capacity. The current state is expected to worsen as more products advance in development and enter the market.

There is a huge amount of activity in CGT Market

While there are a number of obvious obstacles that need to be overcome, all players on the market are intent on coming up with viable solutions. The CGT therapy market is massive and promises huge yields and profits, so it is obviously in the industry’s interest to develop new approaches and technologies in order to alleviate the existing challenges.

After all, the commercialization of CGTs can only be achieved by rethinking existing processes and by utilizing new and emerging solutions. One such solution can be offered by single-use technologies with a high degree of flexibility and scalability, while integrated IT systems allow for monitored and highly precise procedures but also facilitate the collaboration between biomanufacturers, contract development and manufacturing organizations as well as equipment and software vendors.

How Single Use Support can be part of the solution

In order to be viable, any solution offered on the biopharmaceutical market needs to be validated and adhere to the highest standards. From the get-go, Single Use Support has been aware of the need for modular, yet comprehensive solutions that can be adapted and scaled as needed. End-to-end solutions and closed processes are the way forward: On the one hand they offer fragmental benefits across the board that on the other hand can be combined to result in an integral system that covers the entire process from initial development to final logistics, including protection. 

Single Use Support’s freeze-thaw platforms offer insular solutions for the freeze/thaw processes of each clinical phase. The freeze-thaw units are fully scalable and compatible with all batch sizes and bags from all established manufacturers so that in the end customers only require one single system from the lab to blockbuster production.