To say that biomanufacturers owe the volumetric productivity gains of the last decade solely to improvements in cell culture media would be a stretch, but not by much. Media products, feeds, supplements, and additives are areas of intense interest and innovation precisely because their implementation has been so successful.
Many cell culture media today exist as historical relics, notes James Blackwell, Ph.D., senior consultant at BioProcess Technology Consultants. “In the past, we lacked the experimental power to determine if every medium ingredient was actually needed, and if their quantities were optimal.”
Legacy media often contain unnecessary components, or useful ones in insufficient quantities. Some probably hold ingredients that, unknown to processors, inhibit cells or protein expression. “It used to be that if you weren’t sure, you threw it in,” says Dr. Blackwell. High-throughput testing of media components can save money by identifying unnecessary ingredients that may be safely deleted from the mixture.
Culture medium optimization will always involve some degree of trial and error, but high-throughput techniques add systemization and parallelism to these efforts. High-throughput micro- and mini-bioreactor technologies such as Bioprocessors’ SimCell™ platform allow investigators to vary any medium component while holding everything else constant. SimCell runs hundreds of cultures simultaneously, which is useful in selecting production clones, defining process limits, identifying optimum medium and feed conditions, and understanding process variables.
Optimized media formulations dramatically and positively affect media costs, process productivity, and capital investments, and can thereby help justify reengineering of even established processes. Media optimization has the potential to create higher-quality products and a more robust process, in addition to the ability to run smaller or infrequent batches. “The return on investment for a company with several pipeline or commercial products growing rapidly can be tremendous,” says Dr. Blackwell. “Some product companies have been able to scale back on their future capacity demands in this manner and still meet market needs without the huge capital costs of new facilities.”
Belt-Tightening
The cell culture market has experienced belt tightening over the past 18 months, says Hans Huttinga, strategic marketing director for pharma products at Kerry Bio-Science. The company, which sells media supplements for cell culture and microbial fermentation, claims that five of the top biotech blockbusters, and 25% of currently marketed therapeutic protein products, are produced with its culture supplements.
Growth in annual demand for media products, according to Huttinga, has fallen from 15–20% to 7–10%. Some cost-cutting measures are a consequence of current economic conditions, but a fair amount results from biomanufacturers becoming more sophisticated in how they use and acquire media and supplements. Nevertheless, Huttinga believes that all indicators point toward significant growth and “lots of optimism” moving forward.
Kerry develops media supplements that are vegetable-based and serum- or protein-free, but not chemically defined. Products include HyPep™ 1510, a soy-based hydrolysate currently used in several marketed drugs, and UltraPep™ Soy, which provides hydrolyzed carbohydrates in addition to amino acids and peptides. UltraPep is produced enzymatically from soy, wheat, and cottonseed protein sources. The company claims that UltraPep simplifies production processes and gives a more consistent product, but unlike chemically defined media it does not require extensive optimization.