The initial Protein A step used MabSelect SuRe™ resin. Loading at 30 g A Mab/L resin captured >99% of product, but elution at pH 3.5 caused significant aggregation (from 1.5% to 7%).
The final train: . CEX removed aggregates to <0.8%; AEX removed residual DNA (<10 pg/dose) and HCP (<5 ppm).
To demonstrate the application of QbD in bridging bioprocess development with regulatory expectations. A Mab A Case Study In Bioprocess Development
The study uses a hypothetical humanised IgG1 antibody, "A-Mab," designed for IV administration to treat Non-Hodgkin’s Lymphoma.
If upstream is about growing the protein, downstream is about catching it and cleaning it. This is often the most expensive phase of production due to the high cost of resins and chromatography columns. The initial Protein A step used MabSelect SuRe™ resin
Fine depth filter to remove sub-micron particles and colloidal matter.
Centrifugation was bypassed at the commercial 2,000 L scale in favor of a fully single-use depth filtration train. CEX removed aggregates to <0
The study emphasizes optimizing the inoculum expansion and bioreactor stages to enhance productivity while maintaining quality. This includes exploring critical process parameters (CPPs) that directly affect cell growth and antibody glycosylation.
| Step | Resin | Mode | Yield | Purity (monomer) | HCP (ppm) | |------|-------|------|-------|------------------|------------| | CEX | SP Sepharose FF | Bind-elute | 85% | 99.2% | 15 | | AEX | Q Sepharose FF | Flow-through | 92% (no binding) | 98.5% | 8 |
: A "Continuum of Criticality" is used to rank attributes based on their impact on safety and efficacy.