Asymmetrical Flow FFF as an Analytical Tool for the Investigation of the Physical Stability of Virus-Like Particles

During the past few years, virus-like particles gained more and more attention as a new, safe class of vaccines, suitable for the prevention of virus induced infectious diseases (1) and for the therapeutical treatment of chronic diseases (2) and drug addiction (3).

However, for the development of pharmaceutical products based upon virus-like particles (VLPs), the application of reliable analytical tools is of great importance. For quality control purposes, the analytical methods need to be sufficiently sensitive to detect and quantify even small varieties between different active pharmaceutical ingredient (API) bulk materials, and varying formulations upon manufacture and storage. For the assessment of physical properties of viruses and VLPs, three main techniques are established: transmission electron microscopy (TEM) (4–6); dynamic light scattering (DLS), often referred to as photon correlation spectroscopy (PCS) or quasi-elastic light scattering (QELS) (7–9); and size-exclusion chromatography (SEC) (10–12). The utilization of TEM can be ascribed to the high resolution enabling accurate particle analysis. Inherent drawbacks of this technique are random sampling — instead of an overall sample analysis — and time-consuming preparation and measurement procedures.