Achieving a Successful Scale-Down Model and Optimized Economics through Parvovirus Filter Validation using Purified TrueSpikeTM Viruses

Abstract

The safety of biopharmaceuticals is assured through the use of multiple steps in the purification process that are capable of virus clearance, including filtration with virus-retentive filters. The amount of virus present at the downstream stages in the process is expected to be and is typically low. The viral clearance capability of the filtration step is assessed in a validation study. The study utilizes a small version of the larger manufacturing size filter, and a large, known amount of virus is added to the feed prior to filtration. Viral assay before and after filtration allows the virus log reduction value to be quantified. The representativeness of the small-scale model is supported by comparing large-scale filter performance to small-scale filter performance. The large-scale and small-scale filtration runs are performed using the same operating conditions. If the filter performance at both scales is comparable, it supports the applicability of the virus log reduction value obtained with the small-scale filter to the large-scale manufacturing process. However, the virus preparation used to spike the feed material often contains impurities that contribute adversely to virus filter performance in the small-scale model. The added impurities from the virus spike, which are not present at manufacturing scale, compromise the scale-down model and put into question the direct applicability of the virus clearance results. Another consequence of decreased filter performance due to virus spike impurities is the unnecessary over-sizing of the manufacturing system to match the low filter capacity observed in the scale-down model. This article describes how improvements in mammalian virus spike purity ensure the validity of the log reduction value obtained with the scale-down model and support economically optimized filter usage.

Virus filtration: A review of current and future practices in bioprocessing

“…Impurities present in a virus spike can significantly impact product mass or volume throughput in a virus clearance study (De Vilmorin et al, 2015; Slocum et al, 2013). Therefore, high purity and high titer virus stocks are desirable to evaluate virus removal while maintaining product filtration capacity.…”

Viral Filtration: A Review of Current and Future Practices in Bioprocessing

“…In cases where feed material property is affected by freezing and thawing, it is preferable to obtain feed material soon after a manufacturing scale run and use without freezing, or freshly prepare feed from the preceding unit operation at small scale, or filter thawed material to remove any potentially clogging aggregates or particles that result from freezing and thawing. This can result in not achieving the desired volumetric throughput in the validation study Impurities present in a virus spike can significantly impact product mass or volume throughput in a virus clearance study (Slocum, Burnham et al 2013, De Vilmorin, Slocum et al 2015. Therefore, high purity and high titer virus stocks are desirable to evaluate virus removal while maintaining product filtration capacity.…”