FRESH PERSPECTIVES
Selecting the Right SU System As part of Gallus’ selection process, the following criteria were evaluated:
• Ease of scalability
• Commercial production scale off ering (i.e. up to 2000 L) •
Large bioreactor with greater than 4x turndown ration
• Flexibility of operation (e.g. perfusion or batch fed, various cell types)
• Complete SU manufacturing solution (i.e. upstream and downstream)
• Bioreactor and bag technology leadership • Quality reputation
• Prior use in commercial processes to facilitate regulatory path forward
Gallus determined that the FlexFactoryTM platform offering most closely met the requirements and offered the best fit to the selection criteria over other commercially available alternatives due to the following factors:
• Portable turn-key system, including hardware, automation, connectivity and software
• Process service and start-up support
• Timeline less than 9 months from completion of design to build and equip a GMP-ready suite
• 50% lower capital expense compared to conventional investments • The same or better manufacturing quality as stainless bioreactors
• Portable, rapidly deployable, and easily-replicated manufacturing facility
•
Elimination of risk associated with bespoke bioprocessing equipment integration
The availability of a continuous range of bioreactors from 10 L through 2000 L designed for seamless transition from one scale to the next was a key factor. For commercial scale operations, the ability to use multiple 2000 L reactors means saving time and money associated with implementing process changes or improvements.
The fact that the XDR bioreactors in FlexFactory platform are routinely used in perfusion, batch and fed-batch modes with mammalian, microbial and insect cells was also important. These bioreactors employ a novel design that locates the sparging area below and adjacent to the bottom mounted impeller to closely approximate conventional stainless steel stirred-tank bioreactors. This design, combined with the confi gurability of the sparging scheme, enables good control of dissolved oxygen and pH, resulting in enhanced process productivity.
The choice of fi lm in the two-fi lm construction of the bioprocess bags creates a physically robust process environment. Options in bag confi guration for numbers and types of probes, sampling manifolds, multiple exhaust lines, exhaust condenser bags, and baffl es all work together to support specifi c applications and modes of operation.
In addition, the system control software automation platform provides the operator with a highly fl exible interface for assigning fi eld devices, including
48 American Pharmaceutical Review | Fresh Perspectives 2013
pumps and fl ow controllers, to control loops and allows the ability to change setpoints over time.
The FlexFactory platform provides a complete upstream and downstream biomanufacturing solution. The Controlled Environmental Module (CEM) component provides a separate ISO 7 environment for each purifi cation step. The entire manufacturing process can be contained within a single ISO8 hall reducing time and cost for build out. Segregating products and cell lines with single-use downstream processes minimizes change-over and cleaning requirements, thereby, decreasing the risk of contamination.
SU system quality was fundamental to the Gallus selection process. Each element of the FlexFactory platform had been developed with a strong focus on quality, robustness and real-life performance. As the center of the bioprocess manufacturing train, bioreactor quality and robustness are essential and the XDR reactors had been extensively tested with real- life cell lines under production conditions to confi rm performance and robustness. Crucially, the bioprocess bags used by the system were also designed to deliver the required quality and robustness using a validated and reproducible manufacturing process.
This is the fi rst in a series of 3 papers. Subsequent white papers will address qualifi cation of the FlexFactory platform and the implementation for GMP clinical and commercial production runs.
Figure 2
Figure 3 - The GE FlexFactory at Gallus BioPharmaceuticals Clinical Services Suite in St. Louis, Missouri
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