The virus removal or inactivation capacity of a biopharmaceutical manufacturing process should be proven in a virus validation study. Virus spike concentration and purity can potentially affect the LRV obtained. Additionally, such a study can affect the economy of processing. In particular, if the effect of a more concentrated biotherapeutic on virus-validation profile is minimal, the economy of the filtration can increase. A more robust method can affect economy by maintaining reproducibility despite process variation. The effects of varying IgG concentration, PPV purity and PPV percentage of spike on the performance of Planova 20N virus-removal filters were studied. Design of virus clearance studies, as well as safe and economic virus-filter usage, is considered.
Materials and Methods
The Planova 20N flux was not affected by the PPV purity and was identical in the presence and absence of PPV (data not shown). Also, the PPV LRV remained >4 over the filtration volume of 200L/m2 under various spiking conditions. In the non-serum PPV spiking (3vol%) case, a high PPV LRV was maintained past 500L /m2 . (Figure 1) Additionally, for all samples tested, the filtration capacity was not affected by virus purity. (Figure 2)
An inaccurate or poorly designed scale-down model can introduce factors that produce incorrect or uninterpretable results in virus-clearance studies. A higher virus spike percentage can overcome virus-assay limitations; however, this can decrease the filtration performance if not chosen wisely. We routinely recommend PPV spike percentages at contract laboratories up to 1% without problem, and XMuLv spike percentages up to 0.5%. Our data shows that purified virus is not a factor under the conditions studied.