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October 24, 2019

In a previous post we introduced chimeric antigen receptor T-cell (CAR-T) therapy - a new form of cancer therapy based on genetically reprogramming the body’s immune system that has been described as a “breakthrough” and “revolutionary” by the medical and scientific communities.

This post will explore how developing customized solutions for system closure can solve a key technical bottleneck and advance CAR-T manufacturing.

The Challenge for CAR-T Manufacturing

Though promising, CAR-Ts remain costly and largely a difficult manual manufacturing process. CAR-T therapies are currently only available as autologous products. From a manufacturing perspective, autologous therapies represent a “one-shot” opportunity to treat a patient. A failed manufacturing run means a patient may not receive their treatment. Companies like Novartis are responding to this significant problem with the short-term solution of working with regulators to release products to patients on a compassionate care basis, even if they do not meet the expected final release criteria.

To create long-term solutions developers are working on process improvements, like system closure, that will boost safety and reliability, and help to reduce costs.

What Is System Closure and How Is it Accomplished?

A common adage in cell and gene therapy manufacturing is HVC 7 Download Now“the product is the process.” In other words, increasing process efficiency through system closure will improve the final product and therefore reduce costs. What exactly is a closed process? Broadly defined, a closed process uses equipment and consumables that do not expose the product to the outside environment. Further, closed systems allow for new material to be introduced without opening the process. System closure is achieved mainly by selecting or, in some cases, designing hardware that allows a process to remain closed. The right hardware is complemented by reagents that are closed-system compatible (e.g. media provided in bags vs. bottles) and single-use consumables and kits that can be used during all unit operations with sterile, welding-capable tubing.

System Closure Reduces Deviations in the Manufacturing Process

Deviations can be the source of manufacturing failures that result in a patient not receiving their therapy. System closure is one approach used to reduce deviations in the manufacturing process. Other related strategies include increased process automation and addressing the inherent variability in the starting material for autologous products through standardization of inputs.

What Are the Benefits of System Closure?

One of the main drivers for the development of closed systems is the need to mitigate the risk of contamination by containing the living product. This can be accomplished by reducing the need for manual manipulations that occur in an open environment.

Further, open and manual processes are costly due to the requirement for specialized facilities and additional highly trained staff needed to carry out these lengthy manipulations. Closed systems have the potential to reduce these requirements, thus driving down costs.

How Do We Achieve Full-System Closure?

The vision is to create completely closed processes that do not require clean rooms or specialized personnel. We are not there yet, and through a collaboration with GE Healthcare (GEHC) CCRM has developed a unique program focused on innovating to reach this goal. Our team recognizes that closed-system processing will be unique for each product, and therefore has established capabilities that allow for customized closed-system development. For instance, through our collaboration with GEHC we are creating the next generation of products and offering services to address the need for system closure based on feedback from industry. In addition to the collaboration with GEHC, the CCRM team also sources and works with equipment from other vendors and companies so that they have a variety of tools at their disposal to provide the optimal solution. Again, this increases the capacity to create bespoke solutions to meet the evolving needs of therapeutic developers.

Achieving full system closure for CAR-T manufacturing will be a game-changing advancement. Along with process innovation in other areas, it will make CAR-T manufacturing reliable, cost-effective, and ultimately bring this therapy into the mainstream.

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