Wade Nudson, a technical manager at SAFC, discussed his company’s efforts to design effective risk-mitigation strategies for cell culture reagents.
Over the last 20 years, media evaluation has become much more demanding and complex as the number of reagents and media options grows and as more and more production volume shifts to biopharmaceutical uses. Quality control is one of the most pressing concerns.
“We deal with approximately 400 different raw materials in our production schedule,” said Nudson. “We put an enhanced program in place over the last two years that evaluates them analytically and biologically, especially when chemical characterization may not be sufficient.
“We establish dose-response growth curves that are precise and allow accurate, repeatable characterization of our products. We are constantly refining our evaluation procedures, doing a lot more mass spectroscopy, HPLC, and similar studies.”
While the company’s raw materials are purchased only from approved, qualified vendors, quality is not the only issue. There is also availability of the materials used in cell culture.
For example, single-source components like specific plant-derived hydrolysates have experienced supply issues in the past. Any changes in raw materials are carefully planned in advance. Change control and change notification are extremely important in this industry.
“If you lose a bioreactor run in a drug production process because of medium or other raw material failure it could cost the client $50 million in final product or more,” according to Nudson. “Therefore, we make no changes in major components without an extended consultation with the client.”
For single chemicals, it is usually relatively straightforward to check identity and to certify that they are sufficiently pure. For other more complex components, it can be much more difficult. This is a particular problem for undefined components, such as hydrolysates, whose composition is naturally variable, even between batches from the same supplier.
A rule of thumb employed within the industry is that 10–15% biological variability from batch to batch is to be anticipated, and could represent the lower limit of acceptability. To deal with this issue, Nudson describes a chemically defined hydrolysate option offered by SAFC in which the components (such as peptides, amino acids, vitamins, and trace elements) are known and reproducibly formulated.
Investigation of growth parameters has established that this defined medium option supports growth as well or better than the previous undefined product, noted Nudson. This represents a long-term trend in the industry aimed at the eventual elimination of all undefined components in cell culture media formulations.
“That’s what we’re striving for,” Nudson stated, “as this would lessen our dependence on biological assays for quality assurance.”