This system offers the following advantages:
- Completely disposable system components
- Product can be accumulated at extremely high concentrations.
- The system supports the production of enzymes, monoclonal antibodies, therapeutic proteins and a variety of vaccine components
- Cell-culture conditions are optimized for protein production over long periods of time
- Simplified, low cost, serum-free medium can be used, reducing expense, enhancing regulatory compliance, and simplifying downstream
- Cells do not require adaptation to suspension culture, saving time
- Further productivity scale-up can be accomplished by longer culture times, not new equipment
- Culture monitoring sensors are located in the medium reservoir bags, not in the area containing cells, making process monitoring
- Product quality such as protein fidelity may be improved based upon optimized cell culture conditions
- Apoptosis is reduced, further removing cellular proteins and DNA from the harvest supernatant, simplifying downstream processing
- Intensive cleaning involved in traditional stir-tank bioreactors is not an issue
- The small volume of medium present at any time renders control of parameters rapid and efficient.
The large-scale HFBR has the potential to bring all of these advantages to the manufacture of proteins from mammalian cells.
If the oxygen transfer rates are high enough, this system could also be used for some fermentation processes as well. A disposable,
compact replacement for large stirred tanks that produces protein at high concentrations in a simplified, chemically-defined
medium represents a possible paradigm shift in the production of biopharmaceuticals.
The authors gratefully acknowledge the assistance of LaDonna Connors and Gwendolyn Gainer in the preparation of this article.
WILLIAM G. WHITFORD is senior manager, bioprocessing market, Thermo Fisher Scientific, Logan UT, and JOHN J.S. CADWELL* is president and CEO of FiberCell Systems, Frederick, MD, firstname.lastname@example.org
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