FDA has for years urged biomanufacturers to avoid ingredients of animal origin despite the fact that the industry relies heavily on mammalian cell culture production methods. Of 31 therapeutic proteins approved in the U.S. since 2003, 17 are produced in mammalian cells. Suppliers of media, feed, and ingredients have responded with raw media ingredients of plant origin or manufactured through recombinant expression. Animal component-free is also big in stem cell development and regenerative medicine, since tissues are designed for implantation directly into humans.
While regulatory and market pressures are nudging biomanufacturers toward serum-free media for new and older processes alike, diagnostics and academic researchers still rely on classical media based on fetal bovine serum, calf serum, and other serum-based platforms for basic research. And many industrial groups still use animal component-based media for early-stage production of therapeutic proteins and proof-of-principle experiments.
InVitria sells animal component-free recombinant albumin, lactoferrin, and lysozyme for cell culture and microbial fermentation media. Customers include biomanufacturers, media companies, and diagnostics firms. Lactoferrin is a growth factor that CEO Scott Deeter says out-performs insulin and insulin-like growth factors used to boost cell growth and productivity. “It’s a new product, not yet widely used, but we hope to change that.”
At the American Society of Cell Biology annual meeting held last month in San Francisco, InVitria showcased several animal-free and cell-culture medium components for production cells, stem cells, and regenerative medicine, including Cellastim (recombinant albumin) and Lacromin (recombinant lactoferrin).
Deeter describes the surging interest in media as “a positive step toward making media ingredients more consistent and well-defined.” Part of that consistency, he says, involves the use of recombinant ingredients which, unlike batches pooled from serum, are as close in composition as possible. An unanticipated benefit of recombinant components, which have a reputation for high cost, is economy derived from higher productivity and safety, and lower operating and capital costs.
Animal-free media is not a new idea. Its potential benefits were noted, but not realized, from the earliest days of biotechnology. “There were several times during the 1970s and 1980s when experts predicted that animal-free media would revolutionize the industry,” says Jan Baker, CEO of JR Scientific.
It is only in the last decade, however, that the idea really began to catch on for large-scale processes. Many processes, of course, still use animal serum-based media. Serum-free products are less reliable, nutritionally speaking, than those based on animal sera. Biomanufacturers have at times been disappointed with yields and productivity after adapting a serum-based process to serum-free conditions, Baker notes.
“The biotech industry still buys hundreds of thousands of liters of animal sera per year,” he adds. “Classical media are not going away any time soon.”
JR produces media-related consumables, ingredients, and formulated classical and synthetic media, mainly for research labs at universities and biotechnology companies. The company is also a primary OEM supplier to several large companies and provides them with private-labeled animal sera, media, and cell-culture reagent. “Biomanufacturing is already well-served by the major media suppliers,” Baker notes, “which leaves a large portion of the research marketplace for smaller and well-qualified vendors.”
To maintain manufacturing flexibility, JR produces all its media and components in disposable containers to reduce cleaning and cleaning validation at its facility. Disposables are also a selling point, since it reduces the potential for cross-contamination between batches or products.