Viral filtration operations are evaluated and validated using scaled-down models of production processes. In a scaled-down study, a sample of representative process feed is “spiked” with a known quantity of virus to simulate a viral contamination.
Virus removal and hydraulic performance of the spiked feed across a filter are measured, and this data is used to determine the viral clearance capability of the filter as well as the filter size necessary to reach throughput targets at production scale.
Virus spiking can present a challenge because the virus stocks used often contain impurities derived from the cell cultures used to produce them. In fact, many virus preparations consist mainly of nonviral substances that are not relevant to the drug manufacturing process.
These impurities can, in some cases, interact with the filter or feed material to dramatically diminish filter performance, reducing throughput and producing results that do not represent the production-scale process. Furthermore, lot-to-lot variability of virus stock quality can hinder reproducibility and confidence in results.
Consequently, insufficiently purified and characterized virus preparations can cause validation failures.
Researchers at EMD Millipore have developed new methods that produce “ultrapure” virus stocks that have minimal levels of impurities, are high titer, consistent, and well characterized. These improved virus preparations were designed to facilitate validation of Viresolve® Pro Solution filters by minimizing the risk of spike-induced throughput reductions and maximizing consistency of results.
Furthermore, the ability to spike to higher titers will add value by enabling greater virus removal claims.