Rapid Characterization of Virus Solutions for Filter Challenge Studies

Here we describe the use of electrospray differential mobility analysis (ES-DMA) as a process analytical technology (PAT) to characterize the size, concentration, and suitability for filter testing of virus containing solutions. Cell cultures typically used in the production of monoclonal antibodies (mAbs) and therapeutic recombinant proteins (TRPs) produce endogenous type C retrovirus particles and can potentially become infected by adventitious viruses. Biopharmaceutical manufacturing schemes typically include process steps to decrease the viral load including filters, which are membrane-based devices that remove large viruses (e.g. retroviruses) and/or small viruses (e.g. parvoviruses) from product by size exclusion. In 2002, the Parenteral Drug Association (PDA) organized the virus filter task force to develop a common nomenclature and a standardized test method for classifying and identifying viral-retentive filters. In support of this effort, we determined the sizes of several bacteriophages ranging from ~20 nm to ~80 nm including pp7, ΦX174, PR772, and MS2 using ES-DMA. Virus concentration can be assessed with ES-DMA by including an internal particle standard such as gold nanoparticles at a known concentration. This talk will describe the theory of operation of ES-DMA, its use to determine the size and concentration of viral preparations, and its potential application for characterizing vaccines and virus-like particles.