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 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.