Monoclonal antibody production is a tightly controlled process with extensive raw material and cell bank control practices in place to minimize the risk of viral contamination. However, this remains of particular concern because most viruses are small enough to pass through filters used in standard media preparation practices. High-temperature short time (HTST) treatment of media is one technology that can provide another layer of protection against this risk. The following work covers a case study of implementing HTST treatment on media preparation. The industry standard values of 102°C and a 10 second hold time were used. Turbidity mapping and elemental and small molecule analysis of the media before and after HTST treatment were analyzed, giving measurable differences on the makeup of the media using standard preparation methods. Media found to be incompatible with HTST treatment resulted in turbidity increases associated with precipitation, notably calcium and phosphate. Mitigation efforts included (i) assessing drop out media powders with removal of sensitive components, and, (ii) pH ranging studies (from pH 5 to 9). Of note, negligible differences in turbidity analysis before and after HTST treatment were found for media titrated to pH 6. Treated media was used in follow up production bioreactor runs and demonstrated no impact to cell growth, in contrast with the control condition with media that was not HTST compatible and saw a significant decrease in peak viable cell density.

Evaluating implications of high-temperature short time treatment on media component solubility and cell culture performance

253rd National Meeting (2017)

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