Cell culture media, novel resin technologies, and single-use systems are among the most active areas of R&D in the biomanufacturing sector. GEN recently interviewed several scheduled speakers for the upcoming “Bioprocess International Conference” in Long Beach, CA, to get a better sense of how this market is evolving and to see what types of new products are available.
Until the late 1980s, manufacturers of biopharmaceutical products cultured their cells in fetal bovine serum, despite lot-to-lot inconsistency, contamination, and supply issues. With the discovery of bovine spongiform encephalopathy in the late 1980s, and with resulting increases in regulations, manufacturers began to aggressively explore alternatives to serum-based media.
The upshot has been a growing interest in supplements in which all components are entirely chemically defined, animal-free, and protein-free.
In response to this demand, said Samuel Denby, Eng.D., scientific manager for technical applications at BD Biosciences, the company is now marketing BD Recharge™, a chemically defined cell culture media supplement. The product is the first in a series that BD is developing.
“We use proprietary fractionation processes combining analytical methods and bioassays to identify the key components in a yeast extract peptone,” he said. “From these we then selected the optimal chemical constituents for cell nutrition. Although our initial focus has been CHO cell lines, we have several customers evaluating other lines.”
Dr. Denby claimed the product offers equivalent or better yield as compared with traditional peptone supplementation, a reduction in variability while retaining protein quality, and the potential for an easier regulatory filing in biopharmaceutical manufacture.
Supplements need to be evaluated not only for their growth potential but also for their productivity, continued Dr. Denby.
“We typically start with small batch cultures and move up to confirm our results in small-scale bioreactors. In terms of developing our next-generation supplements, pulling the peptones apart is challenging, but putting a chemically defined alternative back together again is equally challenging.
“We use a cross disciplinary team, as well as alpha site evaluations with multiple biopharmaceutical manufacturers who tested the product with production cell lines.”
Among the many factors that determine the suitability of a cell culture medium, two are paramount, noted Tom Fletcher, director of R&D at Irvine Scientific.
“The first is the metabolic behavior of the chosen cell line and the second is the content of the initial growth medium,” he explained.
The company has been rapidly expanding its media production facility. Beginning in the early 1970s Irvine began producing media and researching improvements that resulted in the chemically defined, serum-free products now available.
Because of its many favorable attributes, CHO has become the premier cell line for biopharmaceutical production.
“Most of our work has been with CHO lines, and we have been engaged in a number of collaborative research projects with companies to develop optimal media for specific CHO clones,” Fletcher added. “This has been a boon for us since we find that different CHO clones have undergone significant metabolic alterations and their nutritional requirements may be radically altered.”
According to Fletcher, significant changes have taken place with the opening of a sister facility in Japan, near Tokyo. Located in Saitama prefecture, the plant has the capacity to manufacture animal-component-free cell culture media in volume requirements ranging from research use to industrial scale.
The facility has been commissioned and validated as animal-component-free. The new site is designed to replicate the production and processes used at the company’s Santa Ana, CA, manufacturing facility and is outfitted with the same formulation and packaging equipment.