Below are some answers to Frequently Asked Questions (FAQs) we have received over the years. If you don't see your question here, please Contact Us.
Q: HOW DOES C3'S HOLLOW FIBER (HF) TECHNOLOGY DIFFER FROM OTHER PERFUSION PLATFORMS ON THE MARKET?
A: Many common perfusion platforms utilize hollow fibers as a cell retention mechanism in order to be able to flow media at an acceptable rate. ATF tank attachments, for example, are a common perfusion system that use HFs like a filter, retaining and circulating the cells back into the tank while passing the cell product through the membrane into a holding tank. However, there are several distinct advantages to C3's HF perfusion bioreactor design when comparing to ATF tank systems:
Q: IS THE QUALITY OF THE PROTEIN PRODUCED USING C3'S HOLLOW FIBER PLATFORM EQUIVALENT TO THAT OF FED-BATCH SYSTEMS?
A: At C3 we maintain a high level of quality control and batch release testing. Because each product is custom, we can adjust downstream analytical testing to meet the needs of the individual customer.
In the past, we have had customers switch from tanks to C3’s bioreactors and from C3’s bioreactors back to tanks without changes to the quality of their protein product.
Q: HOW ARE THE BIOREACTORS SAMPLED FOR CELL DENSITY THROUGHOUT THE PROCESS?
A: C3's bioreactors are not sampled for cell density throughout the run, as this is not a key process parameter like it is for batch and fed-batch processes. Unlike tank systems, protein production in HFBR is not limited by cell viability.
C3 has data showing long-term protein production in an HFBR that can last up to 100 days. Throughout these long-term runs, parameters like pH, glucose, and lactate remain consisted after the initial growth curve and allow us to indirectly assess the health of the cells.
Q: WHAT TYPES OF MEDIA CAN BE USED WITH C3'S HOLLOW FIBER PLATFORM?
A: C3's bioreactors have been successfully run with many different commercially available media formulations, including chemically defined, protein free, animal component free, serum-based and serum-free medias.
C3 additionally has a proprietary basal media that has been optimized for use in HFBR for hybridoma cultures and can work with customers to develop appropriate media formulations for their specific cell line and process.
Q: WHAT IS THE SCALE OF PRODUCTION THAT C3 IS ABLE TO HANDLE?
A: C3 is capable of producing proteins in both a GMP and RUO manner in quantities ranging from a few mg to up to a kg of protein product. C3's hollow fiber bioreactors are most cost-effective in the 100s of mg to 1 kg/year range. For smaller quantities of protein, C3 can offer use of more traditional cell culture platforms such as flasks or roller bottles.
Q: HAVE THERE BEEN ANY ISSUES OBSERVED WITH LEACHABLES AND EXTRACTABLES USING C3'S HOLLOW FIBER SYSTEMS?
A: C3 has performed a leachable/extractable study on the the Autovaxid bioreactor system.
The results showed that all levels of extractables and leachables were acceptable for the process supporting a Phase III human therapeutic drug. As with other single use bioreactor systems, each process requires testing as different media, cells and culture conditions (temperature, pH, lactic acid level, time) will have an impact on the L&E levels.
Q: WHAT TYPES OF PROJECTS ARE MOST APPROPRIATE FOR C3'S PERFUSION TECHNOLOGY?
A: C3's HFBR technology is ideal for challenging and small- to mid-scale protein production. Tank-based bioreactor systems are very effective for high-yielding CHO cell lines where IgG production of multiple kg/year is required. However, tanks are often not cost-effective for the production of certain types of challenging molecules and small- to mid-scale projects.
Pre-clinical, toxicology, ex vivo, and clinical trial protein production is challenging to cost-effectively accomplish in a GMP environment. C3's bioreactors are cost-effective and ideal for the mg to kg range of protein production. The small bioreactor footprint, high level of automation, and design of the bioreactors save money on facility usage, labor, and raw materials. We have previously shown that C3's HFBR system can effectively produce difficult-to-express proteins, like many recombinant, chimeric, or fusion proteins. Additionally, low-yielding cell lines, cell lines sensitive to shear stress, or cell lines exhibiting feedback inhibition can produce higher yields in our perfusion bioreactors than they can in tank culture. The small bioreactor footprint and fast turnaround time allowed by the single-use cartridges are also ideal for autologous applications.
Q: WHAT ARE THE ADVANTAGES OF USING A PERFUSION TECHNOLOGY FOR THESE TYPES OF PROJECTS?
A: C3 has a number of case studies demonstrating that production of challenging proteins and cell lines can be dramatically improved by use of C3's perfusion technology:
Q: WHAT IF I DON'T SEE MY ANALYTICAL TEST OF INTERESTED LISTED?
A: We frequently work with customers who have specific analytical needs. If you have an assay or require a test that is not listed on this site, we'd be more than happy to discuss your options here at C3!
Q: Can suspension cells be grown in C3's hollow fiber bioreactors?
A: Yes, we have successfully grown suspension cells as well as adherent cells in our hollow fiber bioreactors. The high cell densities achieved on the extracapillary side (EC) and the low EC perfusion rates allow for a tissue-like environment in which there is minimal sloughing for most cell types.