(475e) The Impact of Cell Culture Media Variability on the Process Development of Biosimilars

Sourcing limitations and the efforts to minimize introduction of adventitious viral or prion agents in the production of biologics have over the years accelerated the adoption of serum-free cell culture media. The subsequent use of animal component free media containing plant derived hydrolysates in cell culture processes has come with observed variability in cell growth, productivity and product quality of biologics. In its purest and supposedly most consistent form, cell culture media has evolved to chemically defined media. As part of a media vendor qualification study, four proprietary media formulations manufactured by five vendors were tested for composition, particle size distribution and solubility characteristics. Media from two vendors were then used in functional cell culture testing.  There was a direct correlation between the media powder particle volume mean diameter (VMD), time to solution and final media turbidity. Differences in media turbidities before and after filtration indicated particulate removal during filtration step, suggesting that some components were not going into solution and therefore unavailable to cells in the bioreactor. Differences between expected and measured levels of media components such as trace metals suggested that there were other extraneous sources of trace elements. Functional cell culture testing results showed that these variations in concentrations of media components had some product quality impact that can affect comparability. Media quality, among other process variables, needs to be controlled for consistency in cell culture process performance.