Viral Vector Manufacturing and Cell Harvesting in a Single Adherent Cell Bioreactor? | Corning

Adherent cell culture is the backbone of an expanding array of therapeutic opportunities, with cell and gene therapies moving through research phases and into clinical practice. After the initial research phases, however, scientists face the challenge of ensuring scalability to deliver quantity and quality with processing consistency. Both cell-based and gene therapies, including viral vector manufacturing, require a volume that is not easy to achieve in traditional planar adherent cell culture environments. Researchers and commercial producers are now looking at fixed bed reactor (FBR) technology to support growth and scalability in upstream bioprocessing.

In response to the need for a higher density adherent cell culture platform, Corning Life Sciences developed the Corning® Ascent™ FBR system. The platform offers automated recirculating bioproduction that not only supports scalability, but also provides flexibility in process development. The closed system can be used outside a laminar flow hood for both adherent cell harvesting and cell product capture.

Optimal Conditions Mean Cells Work Harder

The Ascent FBR system combines the benefits of adherent platforms with the scale and automation of suspension manufacturing systems. As described by Senior Field Application Scientist Austin Mogen, woven mesh bioreactor disks enable uniform media flow, cell distribution and growth within a small footprint.

"With the packed bed and the novel mesh substrate, we've really designed the bioreactor to promote homogenous and equal distribution of cells," says Mogen, before adding that the woven mesh design also optimizes nutrients and oxygen levels throughout the entire reactor.

"And that leads to the cells being happier, so they grow better," he summarizes.

Not only do cells grow more efficiently and at greater density on the woven mesh substrate, the design also optimizes access to transfection and dissociation reagents. Data shows that the system achieves more than 90% transfection efficiency and greater than 90% cell recovery and viability.

Flexibility Covers Multiple Cell Types

Users can centralize workflows and develop standardized protocols that help drive consistency and quality. This single-solution platform supports many applications, including gene therapy and vaccine development in addition to cell harvesting.

The Ascent FBR accommodates viral vector manufacturing using a variety of virus types including adeno-associated virus (AAV), lentivirus, and herpes simplex virus. Feasibility studies show that the platform also supports vero cell growth for viral vaccine and oncolytic herpes simplex virus (HSV) production.

Since the platform also includes cell harvest capability, the Ascent FBR is suitable for stem cell therapy development and has demonstrated successful expansion of both mesenchymal stem cells (MSCs) and pluripotent stem cells (PSC).

Single Platform Flexibility Enables Operational Efficiencies

The ability to switch between cell types also enables project and applications flexibility. Since the same platform handles many applications, there's no need to invest in multiple pieces of equipment and the time spent training personnel on them is reduced. Consumables stocking is simplified, since the same consumables are used for different applications. Optimization can be less time-consuming since operators are already familiar with the system.

Saving space comes not only from the Ascent FBR system supporting different sized bioreactors within the same system but also from being able to handle multiple types of projects on the same equipment. There's no need to buy different platforms specific to cell by-product production when this application can be run on the same instrument that is used for cell harvesting. This can also result in less clean room space required and lower capital investment costs.

Built-In Efficiencies

Increased cell yield and productivity results in fewer culture cycles or "runs" required to achieve the desired output of cells or cell product, and this can translate into reduced media and consumables costs, in addition to saving staff time and labor costs.

It's also worth noting that the Ascent FBR is designed with automation, monitoring and control to optimize for consistently high yields and cell viability.

"The ability to sample is extensive with the Ascent FBR system", says Bioproduction Business Technology Director Tara St. Amand. "It is set up to allow the customer to monitor and gauge cell density," she explains. "There are eight opportunities to sample from the system, with multiple sampling slices of the mesh possible."

This unique sampling ability means you can actually take a sample of the mesh substrate for an in-process cell count. You can also take other samples from the system to give you a broader picture of how the cells are behaving, including inline samples of the media to monitor metabolites such as glucose and lactate.

"This kind of monitoring, along with other data that's generated throughout the run such as the rate of the oxygen consumption, provides real-time insight into how the cells are growing in the system," says St. Amand.

Scalability and the Ascent FBR

Mogen notes that the design of the Ascent FBR also adds to its scalability in that the "plug-and-play" consumables help to minimize the risk of contamination that could be devastating when working at higher volumes.

"The cost of that contamination is higher, because if you have a contamination, you can lose thousands of dollars in reagents pretty readily," he notes.

Starting off a cell production campaign and then scaling up through the Ascent FBR system simplifies subsequent process optimization. There's also less staff training required, as there's no need to switch between platforms to achieve significantly higher yields. Furthermore, contract developers and manufacturers (CDMO/CMO) can benefit from the Ascent FBR system's flexibility to support a variety of different clients with the same system.

"Scalability is a key attribute of the Ascent platform," notes St. Amand. "The [platform's] fluid dynamics allows easy transition from the benchtop to the pilot to the production scale. This is a huge value because it really reduces the time for customers to transition."