Maximally acceptable cellular

Downstream processing involves employment of a purifying system that can isolate the product in as few steps as possible using the simplest purification technology that will achieve the required purity. While purity is a critical consideration for both small-molecule pharmaceuticals and biopharmaceuticals, the nature of biopharmaceutical administration (typically via injection) and the nature of biotechnology processes require that additional considerations be paid to the purity of biopharmaceuticals. The final product must meet regulatory purity and sterility standards and must be below the maximally acceptable cellular or microbial contamination (Ho and Gibaldi, 2003). 

But once the notion of a cytosolic reductive TCA pathway is accepted, the question is why the experimentally obtained yields of C4 organic acids (120-145%, see above, 15.3.1) are lower than the theoretical maximal yield of 200% calculated for this pathway. A plausible explanation for this is that the fungus must divert some of the pyruvic acid carbon to mitochondria and to the oxidative TCA cycle to obtain energy required for maintenance requirements and limited cellular growth (Figure 15.1). 

In the case that the functional cellular target of the lead hits is known and validated, determine the in vitro biochemical half-maximal inhibitory concentrations (IC50) with an accepted assay method. If the capacity for generating this data does not exist institutionally, many fee-for-service resources are available. Without a known target but knowledge of the signaling pathway modulated by the lead hits, a cellular reporter assay can be used in lieu of a biochemical assay however, it is important to keep in mind that compensatory and multimodal effects can confound SAR efforts in cellular systems. These on-target biochemical and cellular assay profiles will serve as potency benchmarks for later SAR and optimization studies. 

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