Particle‐based analysis elucidates the real retention capacities of virus filters and enables optimal virus clearance study design with evaluation systems of diverse virological characteristics

Abstract

In virus clearance study (VCS) design, the amount of virus loaded onto the virus filters (VF) must be carefully controlled. A large amount of virus is required to demonstrate sufficient virus removal capability; however, too high a viral load causes virus breakthrough and reduces log reduction values. We have seen marked variation in the virus removal performance for VFs even with identical VCS design. Understanding how identical virus infectivity, materials and operating conditions can yield such different results is key to optimizing VCS design. The present study developed a particle number‐based method for VCS and investigated the effects on VF performance of discrepancies between apparent virus amount and total particle number of minute virus of mice. Co‐spiking of empty and genome‐containing particles resulted in a decrease in the virus removal performance proportional to the co‐spike ratio. This suggests that empty particles are captured in the same way as genome‐containing particles, competing for retention capacity. In addition, between virus titration methods with about 2.0 Log10 difference in particle‐to‐infectivity ratios, there was a 20‐fold decrease in virus retention capacity limiting the throughput that maintains the required LRV (e.g., 4.0), calculated using infectivity titers. These findings suggest that ignoring virus particle number in VCS design can cause virus overloading and accelerate filter breakthrough. This article asserts the importance of focusing on virus particle number and discusses optimization of VCS design that is unaffected by virological characteristics of evaluation systems and adequately reflect the VF retention capacity.

Integration of Planova filters in manufacturing processes of biologicals improve the virus safety effectively: A review of publicly available data

“…The data presented by Mattila et al 8 and Johnson et al 5 confirm the efficacy of virus filtration, including Planova filters manufactured from regenerated cellulose, for cell culture‐derived proteins and for plasma‐derived medicinal products by Roth et al 6 the parameter protein concentration to be not relevant is also confirmed in these publications. The issue of virus overload—too high virus spike—is known for Planova filters 39 and is not relevant in real life as (i) the virus load in the starting material of plasma‐ and cell culture‐derived products should not exceed predefined limits due to release testing of the starting material of biologicals, that is, plasma pools or the unprocessed bulks (bioreactor harvests), and (ii) a sufficiently high LRF can be achieved using a suitable spike load without overloading the filter, especially when large volume testing is performed to achieve an appropriate limit of detection.…”