Editorial Article
Friday December 04, 2009
The use of cell culture in clinical drug development is rising rapidly due to the advancement of high content analysis techniques and increased large biomolecular therapies. Cell culture consumable requirements for clinical development are more rigorous than for pure research, and a few areas of unmet need remain. These needs include improved plates and wells for adherent cell culture, plates that meet SBS standards for instrument compatibility, and animal-free reagents and media. In addition, cell culture consumables for research or clinical uses must meet high standards for performance, consistency, quality reagent components, safety, and regulatory criteria.
Of all of these considerations, animal-free media is the most problematic. For safety reasons, the FDA recommends that all reagents used in clinical trials be animal-free. However, one component in particular, fetal bovine serum (FBS), is very difficult to replace. It contains important growth factors for the cells and is low in antibodies. In order to replicate the properties of FBS, cell culture media must be carefully formulated to contain all of the individual growth factors. “Single cell isolation and cell line development operations have not easily eliminated animal components, such as FBS, due to the significant negative impact experienced by removing these components. Animal-free and high performance cell line development media is an unmet need,” says Scott Deeter, CEO of InVitria, which offers several newer choices in animal-free cell culture media supplements, including Zap-CHO, Optiferrin, Cellastim, Lacromin, and the soon-to-be launched Zap Hybridoma. These media solve problems such as replacing human- and bovine-derived transferrin, or the need for a customized environment for specialty cell lines such as CHO, HEK293, or primary cell types like keratinocytes, osteoblasts, and fibroblasts.
Another area of rapid innovation in consumables is in surface coatings for plates. “What we find is that there is no one perfect surface for any cell type under any one set of culture conditions. Researchers typically employ an empirical approach in the determination of what works best for their cell type and application,” says Linda Hladik, director of marketing, Discovery Biological Products at BD Biosciences. BD Biosciences’ newest line of cultureware, BD PureCoat™ cultureware, is a family of animal-free, chemically defined plasticware that provides a highly controlled environment for cell culture applications. These new surfaces support BD's broad portfolio of surface treatments that include the BD Falcon™ and BD BioCoat™ branded flasks, dishes, and plates. BD PureCoat cultureware helps take some of the guesswork out of choosing the right surface for the customer. They use a proprietary thin-film coating technology to produce a uniform, functionalized surface on a vessel. BD PureCoat amine and carboxyl surfaces enable better attachment and improved cell proliferation, as compared to standard tissue culture treated surfaces. The BD PureCoat cultureware family of products is available for basic research applications and drug discovery applications that are designed for use in serum-free or serum-reduced conditions.
Greiner Bio-One is a German company that has expanded recently into the North American market. They produce plastics for research, such as flasks, pipettes, and microplates, specializing in sterile, endotoxin-free, RNA- and DNA-free consumables for a very consistent, reliable cell culture result. “All our products are tested and accompanied by quality certificates,” says Sam McCall of Greiner Bio-One. The glass-bottomed CELLview family of products offers enhanced optical properties for high resolution microscopic analysis. The glass bottoms of the wells are autofluorescence-free and come in single-well, or crosshatched subdivided format (to save reagent).
One area that many vendors do not serve is large scale tissue culture products. Biomanufacturing is an underserved market in cell culture consumables, along with stem cell production and single cell isolation, for which animal-free media is slowly becoming available. Another area where more choices are needed in cell culture consumables is in green technologies. Because of the sensitivity of cells grown in culture, plates are generally made of polystyrene, which does not recycle. Additionally, consumables are discarded as biohazardous waste, and few companies are willing to recycle biohazardous materials. Says McCall, “You don't want to sacrifice your research for the consumables. You have to find an intermediate ground, such as green initiatives where we look at minimizing packaging material and minimizing waste.”
Choices in consumables for cell culture now include products customized for specific applications or cell lines, which include technology advancements that improve the science. Significant challenges remain for clinical labware, the greatest of which is finding animal-free media. As well, choices may be slim for large scale cell culture. Many vendors have active development pipelines to address these needs.