Enormous strides have been made in cell and gene therapies. Many potential treatments are now in development, in clinical trials, or even on the market for health conditions that have traditionally been difficult to treat. Much of this research is performed on adherent cells grown on traditional 2D surfaces, which produce relatively small quantities of cells and viruses. Procedures performed on these 2D surfaces often don't scale efficiently, leaving a big gap between obtaining exciting research results and manufacturing enough product to bring a therapy to market at a reasonable cost. Fixed bed bioreactors are helping to close that gap by dramatically increasing capacity and yield without requiring the time-consuming and costly conversion to suspension systems.
Increasing 2D Surface Area
In operations involving adherent cells, methods for scaling up have often focused on increasing 2D surface area without increasing the footprint of the vessel used. For example, the Corning® HYPERFlask® vessel offers 1,720 cm2 of growth area with the same footprint as a traditional T-175 flask by providing 10 interconnected growth surfaces made of a gas-permeable polystyrene. The Corning HYPERStack® vessel also uses ultra-thin gas-permeable layers to produce a closed system with 12 or 36 layers (6,000 cm2 or 18,000 cm2, respectively). They can be manifolded together to increase production and reduce handling time. The Corning CellCube® modules are available with 10 to 100 layers to provide 8,500 cm2 to 85,000 cm2 of surface area. The CellCube system also provides a perfusion-based method to supply oxygen and nutrients, and to remove waste, which mimics the constant fluid flow of in vivo systems. These modular vessel scale-up innovations help to make these adherent platforms highly effective for many applications and as seed train. However, space and manipulation requirements can become challenging when scaling out 2D cell culture vessels to achieve significantly higher cell or vector production targets.
Modern Fixed Bed Bioreactors Offer Flexibility, Speed, and Scalability
A fixed bed reactor (FBR), such as the Corning Ascent® FBR system, consists of a cylindrical vessel, packed with a substrate on which adherent cells attach and grow in 3D space. Culture medium is supplied through a conditioning vessel. While some fixed bed reactors are reusable systems that require cleaning and sterilization, disposable, single-use fixed bed bioreactor vessels, introduced in the past decade, offer improved flexibility, speed, and scalability.
Early single-use FBRs were small-scale, with a maximum cell culture area of between 1 m2 (or 10,000 cm2) and 20 m2 (or 200,000 cm2). The main option for commercial scale manufacturing provided between 0.5 m2 (or 5,000 cm2) and 500 m2 (or 5,000,000 cm2) of cell culture area. However, assessment of these early systems using fluorescent microscopy revealed that many cells form 3D clumps on the growth surface, which reduces viral production compared to cells grown in 2D monolayers.