Overall Chromatographic Process Design Considerations

Key Insight

The optimal design of chromatographic processes is constrained by product quality, process robustness, and economic viability. Product quality requires purities exceeding 99 percent for biopharmaceuticals, with less than 0.5 percent of any individual contaminant. Specific requirements apply to genetic contaminants (especially for animal cell products), endotoxin (for microbial products), and adventitious agents like viruses, prions, bioburden, process chemicals, and aggregates.

Process robustness and reproducibility are crucial for product safety, particularly in biopharmaceutical manufacturing. A key concern is product microheterogeneity, such as glycosylation, which can be affected by process conditions. Since glycosylation impacts bioavailability, pharmacokinetics, and potential toxicity, downstream processing must consider and potentially be designed to achieve desired glycosylation patterns by separating undesirable isoforms.

Economic viability depends on product yield, process productivity, consumption of solvents and process chemicals, labor, and depreciation. Multi-step biopharmaceutical processes necessitate individual step yields greater than 90 percent to achieve acceptable overall yields. Productivity, defined as the amount of product processed per unit time and stationary phase volume, significantly impacts total costs. Comprehensive optimization balances technical, regulatory, and economic factors, often prioritizing maximum productivity when the cost of the stationary phase is dominant.