Scale-Up and Comparison Studies Evaluating Disposable Bioreactors and Probes - Process performance was comparable across all scales, and fiber optic sensors appeared interchangeable with conventional

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Scale-Up and Comparison Studies Evaluating Disposable Bioreactors and Probes
Process performance was comparable across all scales, and fiber optic sensors appeared interchangeable with conventional probes.


BioPharm International Supplements


Abstract

Acceleron Pharma has based its manufacturing platform on disposable technology for cell culture, harvest, and purification. Cell culture was originally performed in GE WAVE bioreactors; however, as the demand for material increased, the need for a more robust, more tightly controlled system became essential. Acceleron chose to maintain disposability and purchased the HyClone stirred-tank single-use bioreactor (SUB) for process development with the goal of implementing the SUB into a new manufacturing facility based on disposable technology. Four 2-L Applikon and two 5-L Sartorius Stedim glass vessel stirred-tank reactors were used for small scale development, process optimization, and comparison between the traditional bioreactor and the disposable technology. Temperature, pH, and dissolved oxygen (DO) were controlled, and nutrients, metabolites, and gases were monitored off-line using a Nova BioProfile Flex. The 50-L and 250-L SUBs were used for scale-up and pilot runs with the optimized process (a 14-day fed-batch culture). Data on cell density, fractional viability, and protein concentration were collected and compared across the scales and types of reactors. The oxygen mass transfer coefficient (ka) was also compared from vessel to vessel to aid in scaling up from the glass vessels to the SUBs. More recently, a 1,000-L SUB, integrated with a Finesse controller, was used for engineering runs. In addition to disposable vessel technology, studies were performed that compared fiber optic DO probes and sensors (which have the option of being disposable), to autoclavable polarographic probes. The preliminary studies indicate that the fiber optic technologies are interchangeable with the conventional polarographic probes. Based on this work, disposable technology was determined to be a desirable option for biopharmaceutical manufacturing at Acceleron Pharma.


Acceleron Pharma
Acceleron Pharma is a privately held company based in Cambridge, MA, developing novel bio-therapeutics focused on the growth and differentiation factor (GDF) family of proteins. To minimize capital and validation costs, Acceleron implemented disposable equipment—mainly disposable bioreactors and harvest and purification equipment—into the development and manufacturing platform. Originally, cell culture was performed in WAVE bioreactors (GE Healthcare). However, because of limitations on control and scalability, a more robust system became necessary. The stirred-tank single-use bioreactor (SUB) by HyClone (Thermo Fisher) provided a stirred-tank design with the ability to control, monitor, and log data throughout cell culture when integrated with a control system. Using glass vessel reactors as a comparison, the SUBs were evaluated in scale-up studies to determine the applicability of the disposable design.

In addition, to simplify the manufacturing process and create a completely disposable environment for cell culture, disposable dissolved oxygen (DO) probes and the fiber optic technology associated with them were evaluated. The fiber optic probes were compared directly with the traditional polarographic DO probes.


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