BIOT 161 |
| Viral clearance using disposable membrane adsorbers has evolved into a method of choice for many in protein therapeutics manufacture. However, little work has been done to understand this separation at the molecular-level, and no mechanistic model exists to predict viral clearance based on system parameter values. In this work, we used surface plasmon resonance to measure directly the adsorption kinetics between the immobilized ligand used in membrane adsorber products and the impurity molecules in solution such as virus and DNA. Next, we measured breakthrough curves and log reduction values for DNA and model bacteriophage viruses using a small-scale membrane adsorber. We compared these experimental observations to predictions from two diametrically opposed mathematical models: (1) adsorption kinetics controls performance, and (2) equilibrium sorption controls performance. The results of these studies indicate that the adsorption kinetics are not the rate-limiting factor, and that impurity-ligand solution equilibrium may be an important factor. However, not all observations can be explained perfectly using these models, and there is much we still do not understand about the science of viral clearance operations using membrane adsorbers. |
|
Downstream Processing: Molecular Interactions and Modeling Approaches
3:00 PM-5:20 PM, Tuesday, August 21, 2007 BCEC -- 106, Oral
Division of Biochemical Technology |