One of the key barriers to generating long and productive mammalian fed-batch cell cultures is the accumulation of growth- and protein production- inhibitory metabolic waste byproducts such as ammonium and lactate. One popular method for reducing ammonium is to remove glutamine from the cell culture medium. However, not all biopharmaceutical cell lines are capable of synthesizing glutamine de novo. Thus, there is a need for a method to reduce waste accumulation irrespective of whether the cell culture medium contains glutamine.<br/><br/>In this work, we describe the effects of component A and component B on the waste byproduct accumulation of two cell lines. The main benefit of cultures exhibiting reduced ammonia and lactate profiles is that these conditions yield longer-lasting and more productive (higher titer) fed-batch cell culture processes. Feeding component A to cell line 1 results in 50% higher titer at harvest. Feeding component A and/or component B can decrease ammonia accumulation for cell line 2. Feeding both components A and B to cell line 2 results in longer, more consistent and more productive mammalian cell culture processes that produce 10 g/L titers. Furthermore, addition of component A and component B together can also decrease the accumulation of both ammonia and lactate and prevent the premature cell viability decline often observed in overfed cultures due to ammonium toxicity. Overall, components A and B were found to decrease waste accumulation and increase process consistency and robustness.

Media components for reducing waste accumulation in mammalian cell culture

249th National Meeting (2015)

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